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Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine
the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-1811 as
monotherapy and in combination with zimberelimab in participants with advanced solid tumors.
This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D:
combination therapy, and Part F for both monotherapy and combination therapy) in participants
with advanced solid tumors who have received, been intolerant to, or been ineligible for all
treatments known to confer clinical benefit or in participants with select solid tumors.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05007782
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Key
Inclusion Criteria:
• Disease:
• Part A: Individuals with histologically or cytologically confirmed advanced solid
tumors who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit.
• Part B: Individuals with histologically or cytologically confirmed select
indications who have received, been intolerant to, or been ineligible for all
treatment known to confer clinical benefit.
• Part C: Individuals with histologically or cytologically confirmed advanced solid
tumors who have received, been intolerant to, or been ineligible for all
treatments known to confer clinical benefit or whose disease is indicated for
anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-[L]1)
monoclonal antibody monotherapy.
• Part D: Individuals with pathologically confirmed select advanced solid tumors.
• Part E: Individuals with pathologically confirmed select advanced solid tumors.
Participants must have received, have been intolerant to, or have been ineligible
for all treatment known to confer clinical benefit.
• Part F: Individuals with pathologically-confirmed select advanced solid tumors.
Participants must have received, have been intolerant to, or have been ineligible
for all treatments known to confer clinical benefit; or, for participants who
will undergo combination therapy, have disease which is indicated for
anti-PD-(L)1 mAb monotherapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for
individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F.
• Adequate organ function.
• Male individuals and female individuals of childbearing potential who engage in
heterosexual intercourse must agree to use methods of contraception.
• Tissue requirement:
• Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample
prior to enrollment.
• Part B and select participants in Parts C and F: Must have fresh pre-treatment
and on-treatment biopsies for biomarker analysis.
Key
Exclusion Criteria:
• Concurrent anticancer treatment.
• Any anti-cancer therapy, whether investigational or approved, within protocol
specified time prior to initiation of study including: immunotherapy or biologic
therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14
days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21
days).
• Any prior CCR8 directed therapy.
• Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell
transplantation. Exception: prior corneal transplant without requirement for systemic
immunosuppressive agents is allowed.
• Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected
carcinoma in situ, localized prostate cancer, or superficial bladder cancer after
undergoing potentially curative therapy with no evidence of disease. Individuals with
other previous malignancies are eligible if disease-free for > 2 years.
• History of intolerance, hypersensitivity, or treatment discontinuation due to severe
immune-related adverse events (irAEs) on prior immunotherapy.
• History of autoimmune disease or active autoimmune disease requiring systemic
treatment within 2 years.
• History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis
(excluding localized radiation pneumonitis).
• Active and clinically relevant bacterial, fungal, or viral infection that is not
controlled or requires IV antibiotics.
• Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human
immunodeficiency virus (HIV).
• Positive serum pregnancy test or breastfeeding female.
• Live vaccines within 30 days prior to first dose.
• Significant cardiovascular disease.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus, Advanced Solid Tumor
Study of DF1001 in Patients With Advanced Solid Tumors
DF1001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell
activation signals to specific receptors on cancer cells. The study will occur in two phases.
The first phase will be a dose escalation phase, enrolling patients with various types of
solid tumors that express human epidermal growth factor receptor 2 (HER2). The second phase
will include a dose expansion using the best dose selected from the first phase of the study.
Multiple cohorts will be opened with eligible patients having either HER2 activated non-small
cell lung cancer, hormone receptor (HR) positive HER2 negative metastatic breast cancer, or
HER2 positive metastatic breast cancer. DF1001-001 will be administered as monotherapy or in
combination; combinations are DF1001 + nivolumab, DF1001 + Nab paclitaxel, and DF1001 +
sacituzumab govitecan-hziy.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04143711
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Inclusion Criteria:
General (applies to all cohorts)
1. Signed written informed consent.
2. Male or female patients aged ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
and an estimated life expectancy of at least 3 months.
4. Baseline Left Ventricular Ejection Fraction (LVEF) ≥ 55% measured by echocardiography
(preferred) or multigated acquisition (MUGA) scan.
5. Adequate hematological function.
6. Adequate hepatic function.
7. Adequate renal function.
8. Effective contraception for women of child bearing potential (WOCBP) patients as
defined by World Health Organization (WHO) guidelines for 1 "highly effective" method
or 2 "effective" methods.
Inclusion Criteria:
NSCLC (HER2 Activated) Exploratory Efficacy Cohorts •Monotherapy and
Combination with Sacituzumab Govitecan-hziy.
1. Have progression of unresectable locally advanced or metastatic NSCLC after last
systemic therapy (as confirmed by investigator) or be intolerant of last systemic
therapy.
2. Have HER2 overexpression status (IHC 2+ or 3+), or ERBB2 amplification, or HER2
activating mutation
3. Have recurrent or progressive disease during or after platinum doublet-based
chemotherapy.
4. Have received and progressed on or after anti-PD-(L)1 therapy.
Inclusion Criteria:
Metastatic Breast Cancer (HR+/HER2-) Exploratory Efficacy Cohort -
Monotherapy and Combination with Sacituzumab Govitecan-hziy.
1. Documented evidence of HR+ metastatic breast cancer
2. Documented evidence of HER2- status.
3. Disease progression or recurrence after prior therapy.
Inclusion Criteria:
Metastatic Breast Cancer (HER2+) Exploratory Efficacy Cohorts -
Combination with Sacituzumab Govitecan-hziy
1. Have histologically confirmed HER2+ breast cancer.
2. Have received prior treatment with trastuzumab, pertuzumab, ado-trastuzumab emtansine
(T-DM1), or trastuzumab deruxtecan (T-DXd).
3. Have progression of unresectable locally advanced metastatic breast cancer after last
systemic therapy or be intolerant of last systemic therapy.
Inclusion Criteria:
Dose Escalation
1. Evidence of objective disease, but participation does not require a measurable lesion.
2. Locally advanced or metastatic solid tumors, for which no standard therapy exists, or
standard therapy has failed.
3. HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2
activating mutations.
Inclusion Criteria:
"3+3" Nivolumab Combination Cohort
1. Eligible to receive nivolumab per its label for a malignancy of epithelial origin; or
2. Have no standard therapy available, or standard therapy has failed, and must not have
received nivolumab prior to joining the study.
3. HER2 expression by immunohistochemistry and/or ebb2 amplification and/or erbb2
activating mutations must be documented on either archival tissue or fresh tumor
biopsy.
Inclusion Criteria:
"3+3" Nab paclitaxel Combination Cohort
1. Patients must be eligible for treatment with nab-paclitaxel per its label, or have no
standard therapy available, or standard therapy has failed.
2. HER2 expression by immunohistochemistry and/or erbb2 amplification and/or erbb2
activating mutations must be documented on either archival tissue or fresh tumor
biopsy.
Inclusion Criteria:
Safety/PK/PD Expansion Cohorts (Monotherapy and Combination Therapy).
1. Fresh tumor biopsy must be obtained during the screening window.
2. HER2 expression by immunohistochemistry (IHC).
3. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
Inclusion Criteria:
Urothelial Bladder Cancer Expansion Cohort(s).
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically or cytologically documented locally advanced or metastatic transitional
cell carcinoma of the urothelium (including renal pelvis, ureters, urinary urothelial,
urethra).
3. Patients must have received a platinum containing chemotherapy and an anti PD-1 or
anti PD-L1 for the treatment of urothelial bladder cancer.
Inclusion Criteria:
Breast Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1
2. Histologically documented (metastatic or locally advanced) breast cancer.
3. Absence of erbb2 amplification by ISH and/or HER2 IHC of 0, 1+, or 2+.
4. Patient must have progressed after one line of systemic chemotherapy.
Inclusion Criteria:
Breast Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1
2. Histologically documented (metastatic or locally advanced) breast cancer.
3. Erbb2 amplification by ISH and/or HER2 IHC of 3+, or 2+. If Herceptest score is 2+,
ISH results should demonstrate erbb2 amplification.
Inclusion Criteria:
Basket erbb2 amplified Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Documented history of erbb2 amplification.
3. Patients must have received at least one line of an approved or established therapy.
Inclusion Criteria:
Gastric Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) gastric cancer or cancer of the
gastro-esophageal junction.
3. Tumor must have been declared HER2 positive.
Inclusion Criteria:
Gastric Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) gastric cancer or cancer of the
gastro-esophageal junction.
3. Tumor must have been declared HER2 low; ISH non-amplified and/or HER2 IHC of 0, 1+ or
2+. If Herceptest score is 0, HER2 must be detected by IHC on at least 1+ of the tumor
cells.
Inclusion Criteria:
Esophageal Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) esophageal cancer.
3. Tumor must have been declared HER2 positive.
Inclusion Criteria:
Esophageal Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Advanced (unresectable/recurrent/metastatic) esophageal cancer.
3. Tumor must have been declared HER2 low; ISH non-amplified and/or HER2 IHC of 0, 1+ or
2+. If Herceptest score is 0, HER2 must be detected by IHC on at least 1+ of the tumor
cells.
Inclusion Criteria:
Non-small Cell Lung Cancer (HER2 Low) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or
recurrent disease that has been confirmed to have HER2 expression (at least 1+,
however, patients must not carry an erbb2 amplification) via archival or fresh biopsy
tissue prior to study enrollment.
3. Patients must have recurrent or progressive disease during or after platinum
doublet-based chemotherapy.
Inclusion Criteria:
Non-small Cell Lung Cancer (HER2 High) Expansion Cohort
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IV, or
recurrent disease that has been confirmed to have amplification of erbb2 via archival
or fresh biopsy tissue prior to study enrollment.
3. Patients must have recurrent or progressive disease during or after platinum
doublet-based chemotherapy.
Exclusion Criteria:
1. Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [with the
exception of palliative bone directed radiotherapy], immune therapy, or cytokine
therapy except for erythropoietin), major surgery (excluding prior diagnostic biopsy),
concurrent systemic therapy with steroids or other immunosuppressive agents, or use of
any investigational drug within 28 days or 5 half-lives before the start of study
treatment. Note: Patients receiving bisphosphonates are eligible provided treatment
was initiated at least 14 days before the first dose of DF1001.
2. Previous malignant disease other than the target malignancy to be investigated in this
study within the last 3 years, with the exception of basal or squamous cell carcinoma
of the skin or cervical carcinoma in situ.
3. Rapidly progressive disease.
4. Active or history of central nervous system (CNS) metastases.
5. Receipt of any organ transplantation including autologous or allogeneic stem-cell
transplantation.
6. Significant acute or chronic infections (including historic positive test for human
immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C
tested during the screening window).
7. Preexisting autoimmune disease (except for patients with vitiligo) needing treatment
with systemic immunosuppressive agents for more than 28 days within the last 3 years
or clinically relevant immunodeficiencies (eg, dys-gammaglobulinemia or congenital
immunodeficiencies), or fever within 7 days of Day 1.
8. Known severe hypersensitivity reactions to mAbs (≥ Grade 3 NCI-CTCAE v5.0), any
history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly
controlled asthma).
9. Persisting toxicity related to prior therapy > Grade 1 NCI-CTCAE v5.0, however
alopecia and sensory neuropathy ≤ Grade 2 is acceptable.
10. Pregnancy or lactation in females during the study.
11. Known alcohol or drug abuse.
12. Serious cardiac illness
13. NYHA III of IV heart failure or systolic dysfunction (LVEF < 55%)
14. High-risk uncontrolled arrhythmias ie, tachycardia with a heart rate > 100/min at rest
15. Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade
Atrioventricular block (AV-block; second-degree AV-block Type 2 [Mobitz 2] or
third-degree AV-block)
16. Angina pectoris requiring anti-anginal medication
17. Clinically significant valvular heart disease
18. Evidence of transmural infarction on ECG
19. Poorly controlled hypertension (defined by: systolic > 180 mm Hg or diastolic > 100 mm
Hg)
20. Clinically relevant uncontrolled cardiac risk factors, clinically relevant pulmonary
disease or any clinically relevant medical condition in the opinion of the
Investigator that may limit participation in this study.
21. Severe dyspnea at rest due to complications of advanced malignancy or requiring
supplementary oxygen therapy.
22. All other significant diseases (e.g., inflammatory bowel disease), which, in the
opinion of the Investigator, might impair the patient's ability to participate
23. Any psychiatric condition that would prohibit the understanding or rendering of
informed consent.
24. Legal incapacity or limited legal capacity.
25. Incapable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol .
Solid Tumor, Adult, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
De-Escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA) (DEBRA)
This Phase III Trial evaluates whether breast conservation surgery and endocrine therapy
results in a non-inferior rate of invasive or non-invasive ipsilateral breast tumor
recurrence (IBTR) compared to breast conservation with breast radiation and endocrine
therapy.
Bethany Anderson, MD
All
50 Years to 70 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04852887
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Inclusion Criteria:
• • The patient or a legally authorized representative must provide study-specific
informed consent prior to pre-entry/Step 1 and, for patients treated in the U.S.,
authorization permitting release of personal health information.
• The patient must have an ECOG performance status of 0 or 1.
• The patient must have undergone a lumpectomy and the margins of the resected
specimen or re-excision must be histologically free of invasive tumor and DCIS
with no ink on tumor as determined by the local pathologist. If pathologic
examination demonstrates tumor at the line of resection, additional excisions may
be performed to obtain clear margins. (Patients with margins positive for LCIS
are eligible without additional resection.)
• The tumor must be unilateral invasive adenocarcinoma of the breast on histologic
examination.
• Patient must have undergone axillary staging (sentinel node biopsy and/or
axillary node dissection).
• The following staging criteria must be met postoperatively according to AJCC 8th
edition criteria:
• By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm).
• By pathologic evaluation, ipsilateral nodes must be pN0. (Patients with
pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible.)
• Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core
biopsy or resected specimen.
** For patients with a T1a tumor (less than or equal to 0.5 cm in size) or
patients at Canadian provinces or approved international sites where Oncotype DX
Recurrence Score testing would not be covered, who do not already have an
Oncotype DX Recurrence Score at pre-entry/Step 1, a specimen (unstained blocks or
slides) must be sent to the Genomic Health centralized laboratory. Tumor size
sample must be greater than or equal to 0.2 cm for analysis.
*** The Oncotype RS can be run on the biopsy core or surgical specimen. The
patient cannot have initiated endocrine therapy prior to tissue collection.
• An Oncotype RS is required for eligibility, however, for a patient whose tumor
has already had a MammaPrint test completed as part of usual care when being
considered for enrollment and is in the binary "Low" category will meet this
eligibility criteria and an Oncotype RS does not need to be performed.
• The tumor must have been determined to be ER and/or PgR positive assessed by
current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients
with greater than or equal to 1% ER or PgR staining by IHC are considered
positive.
• The tumor must have been determined to be HER2-negative by current ASCO/CAP
guidelines.
• Patients may be premenopausal or postmenopausal at the time of pre-entry/Step 1.
For study purposes, postmenopausal is defined as:
• Age 56 or older with no spontaneous menses for at least 12 months prior to
pre-entry/Step 1; or a documented hysterectomy; or
• Age 55 or younger with no spontaneous menses for at least 12 months prior to
pre-entry/Step 1 (e.g., spontaneous or secondary to hysterectomy) and with a
documented estradiol level in the postmenopausal range according to local
institutional/laboratory standard; or Documented bilateral oophorectomy.
• The interval between the last surgery for breast cancer (including re-excision of
margins) and pre-entry/Step 1 must be no more than 70 days.
• The patient must have recovered from surgery with the incision completely healed
and no signs of infection.
• Bilateral mammogram or MRI within 6 months prior to pre-entry/Step 1.
HIV-infected patients on effective anti-retroviral therapy with undetectable
viral load within 6 months are eligible for this trial. Patients must be
intending to take endocrine therapy for a minimum 5 years duration (tamoxifen or
aromatase inhibitor). The specific regimen of endocrine therapy is at the
treating physician's discretion.
Exclusion Criteria:
• • Definitive clinical or radiologic evidence of metastatic disease.
• pT1 mi and pT2 •pT4 tumors including inflammatory breast cancer.
• Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
• Patient had a mastectomy.
• Palpable or radiographically suspicious ipsilateral or contralateral axillary,
supraclavicular, infraclavicular, or internal mammary nodes, unless there is
histologic confirmation that these nodes are negative for tumor.
• Suspicious microcalcifications, densities, or palpable abnormalities (in the
ipsilateral or contralateral breast) unless biopsied and found to be benign.
• Non-epithelial breast malignancies such as sarcoma or lymphoma.
• Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant
or separated by 4 or more centimeters. (Patients with multifocal carcinoma are
eligible.)
• Paget's disease of the nipple.
• Any history, not including the index cancer, of ipsilateral invasive breast
cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or
previous ipsilateral LCIS are eligible.)
• Synchronous or previous contralateral invasive breast cancer or DCIS. (Patients
with synchronous and/or previous contralateral LCIS are eligible.)
• Surgical margins that cannot be microscopically assessed or are positive at
pathologic evaluation. (If surgical margins are rendered free of disease by re-
excision, the patient is eligible.)
• Treatment plan that includes regional nodal irradiation.
• Any treatment with radiation therapy, chemotherapy, or biotherapy, administered
for the currently diagnosed breast cancer prior to pre-entry/Step 1.
• History of non-breast malignancies (except for in situ cancers treated only by
local excision and basal cell and squamous cell carcinomas of the skin) within 5
years prior to pre-entry/Step 1.
• Current therapy with any endocrine therapy such as raloxifene (Evista®),
tamoxifen, or other selective estrogen receptor modulators (SERMs), either for
osteoporosis or breast cancer prevention.
** Patients are eligible for BR007 if they receive a short course of preoperative
endocrine therapy of less than 6 weeks duration (prior to randomization/Step 2)
for this diagnosis after the core biopsy (and can continue postoperatively if:
• the Oncotype DX Recurrence Score is assessed on the biopsy core and is less than
or equal to 18, AND
• the patient had not initiated endocrine therapy prior to core biopsy tissue
collection.
*** This does not apply to adjuvant endocrine therapy recommended for this
diagnosis which may start any time after surgery including prior to registration
(Pre-entry/Step 1).
• Patients intending to continue on oral, transdermal, or subdermal estrogen
replacement (including all estrogen only and estrogen-progesterone formulas) are
not eligible. Patients that discontinue oral, transdermal, or subdermal estrogen
replacement prior to registration are eligible.
• Prior breast or thoracic RT for any condition.
• Active collagen vascular disease, specifically dermatomyositis with a CPK level
above normal or with an active skin rash, systemic lupus erythematosis, or
scleroderma.
• Pregnancy or lactation at the time of pre-entry/Step 1 or intention to become
pregnant during treatment. (Note: Pregnancy testing according to institutional
standards for women of childbearing potential must be performed within 2 weeks
prior to pre-entry/Step 1.)
• Any other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of study therapy or that may affect the
interpretation of the results or render the patient at high risk from treatment
complications.
• Psychiatric or addictive disorders or other conditions that, in the opinion of
the investigator, would preclude the patient from meeting the study requirements
or interfere with interpretation of study results.
• Use of any investigational product within 30 days prior to pre-entry/Step 1.
Vitamin A Status in Patients With Vocal Fold Leukoplakia
This study will determine systemic vitamin A status and lesion histopathology of participants
with vocal fold hyperkeratosis resulting in clinical leukoplakia.
Nathan Welham
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT05323292
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Inclusion Criteria:
1. Willing to provide informed consent.
2. Willing to comply with all study procedures and be available for the duration of the
study.
3. Ability to take oral medication.
4. At least 18 years of age.
5. Leukoplakia study groups:
1. Leukoplakia due to hyperkeratosis with dysplasia: biopsy-confirmed diagnosis of
hyperkeratosis with dysplasia.
2. Leukoplakia due to hyperkeratosis with no dysplasia: biopsy-confirmed diagnosis
of hyperkeratosis with no dysplasia.
6. Control group: Laryngoscopy showing no evidence of vocal fold mucosal disease.
Exclusion Criteria:
1. History of malignant vocal fold mucosal pathology.
2. History of metabolic or liver disorder.
3. History of anorexia or bulimia.
4. Pregnant, lactating, or planning on becoming pregnant during the study period.
5. History of >4.5 kg weight loss in the past 90 days.
6. Medical or other inability to complete an 8 hour fast.
7. Acute respiratory or gastrointestinal illness.
8. Currently incarcerated.
9. Impaired decision-making capacity.
10. No or limited English speaking ability; illiterate or low-literacy ability.
11. Profound visual or hearing impairment that limits written or verbal communication.
12. Status relationship with a member of the study team.
13. Not suitable for study participation due to other reasons at the discretion of the
investigators.
Diseases of vocal cords and larynx, Other, Vitamin A, Vitamin A Deficiency, Leukoplakia, Vocal Cord Neoplasm, Healthy Volunteers, Food & Nutrition
Testing if High Dose Radiation Only to the Sites of Brain Cancer Compared to Whole Brain Radiation That Avoids the Hippocampus is Better at Preventing Loss of Memory and Thinking Ability
This phase III trial compares the effect of stereotactic radiosurgery to standard of care
memantine and whole brain radiation therapy that avoids the hippocampus (the memory zone of
the brain) for the treatment of small cell lung cancer that has spread to the brain.
Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high
dose of radiation directly to the tumor and may cause less damage to normal tissue. Whole
brain radiation therapy delivers a low dose of radiation to the entire brain including the
normal brain tissue. Hippocampal avoidance during whole-brain radiation therapy (HA-WBRT)
decreases the amount of radiation that is delivered to the hippocampus which is a brain
structure that is important for memory. The drug, memantine, is also often given with whole
brain radiotherapy because it may decrease the risk of side effects related to thinking and
memory. Stereotactic radiosurgery may decrease side effects related to memory and thinking
compared to standard of care HA-WBRT plus memantine.
Andrew Baschnagel, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04804644
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Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of small cell lung
cancer within 5 years of registration. If the original histologic proof of malignancy
is greater than 5 years, then pathological (i.e., more recent) confirmation is
required (e.g., from a systemic or brain metastasis);
• Patients with de novo or recurrent small cell lung cancer are permitted.
• Ten or fewer brain metastases ≤ 3 cm in largest diameter and outside a 5-mm margin
around either hippocampus must be visible on contrast-enhanced magnetic resonance
imaging (MRI) performed ≤ 21 days prior to study entry.
• Brain metastases can be diagnosed synchronous to the initial diagnosis of small
cell lung cancer or metachronous to the initial diagnosis and management of small
cell lung cancer.
• The total tumor volume must be 30 cm^3 or less. Lesion volume will be
approximated by measuring the lesion's three perpendicular diameters on contrast
enhanced, T1-weighted MRI and the product of those diameters will be divided by 2
to estimate the lesion volume (e.g. xyz/2). Alternatively, direct volumetric
measurements via slice by slice contouring on a treatment planning software
package can be used to calculate the total tumor volume.
• Brain metastases must be diagnosed on MRI, which will include the following
elements:
• REQUIRED MRI ELEMENTS
• Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D)
spoiled gradient (SPGR). Acceptable 3D SPGR sequences include
magnetization prepared 3D gradient recalled echo (GRE) rapid gradient
echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (Brain Volume
Imaging) or 3D Fast FE (field echo). The T1-weighted 3D scan should use
the smallest possible axial slice thickness, not to exceed 1.5 mm.
• Pre-contrast T1 weighted imaging (3D imaging sequence strongly
encouraged).
• A minimum of one axial T2 FLAIR (preferred) or T2 sequence is required.
This can be acquired as a two dimensional (2D) or 3D image. If 2D, the
images should be obtained in the axial plane.
• ADDITIONAL RECOMMENDATIONS
• Recommendation is that an axial T2 FLAIR (preferred) sequence be
performed instead of a T2 sequence.
• Recommendation is that that pre-contrast 3D T1 be performed with the
same parameters as the post-contrast 3D T1.
• Recommendation is that imaging be performed on a 3 Tesla (3T) MRI.
• Recommendation is that the study participants be scanned on the same
MRI instrument at each time point.
• Recommendation is that if additional sequences are obtained, these
should meet the criteria outlined in Kaufmann et al., 2020.
• If additional sequences are obtained, total imaging time should not
exceed 60 minutes.
• History/physical examination
• Age ≥ 18
• Karnofsky performance status of ≥ 70
• Creatinine clearance ≥ 30 ml/min
• Following the diagnosis of brain metastases, patients can initiate and treat with
systemic (chemotherapy and/or immunotherapy) before enrollment only if their brain
metastases are asymptomatic and not located in eloquent locations (e.g., brainstem,
pre-/post-central gyrus, visual cortex). However, within 21 days prior to enrollment,
brain MRI must be repeated to confirm eligibility.
• Patients with symptomatic brain metastases and/or brain metastases in eloquent
locations (e.g., brainstem, pre-/post central gyrus, visual cortex) are eligible
for enrollment on the trial; however, the specific treatment approach of starting
with systemic therapy alone and delaying brain radiation is not recommended for
these patients.
• Concurrent immunotherapy with brain radiation (SRS or HA-WBRT) is permitted.
• Negative urine or serum pregnancy test (in women of childbearing potential) within 14
days prior to registration. Women of childbearing potential and men who are sexually
active must use contraception while on study.
• Patients may have had prior intracranial surgical resection. Patients must have
completed prior intracranial surgical resection at least 14 days prior to
registration.
• Because neurocognitive testing is the primary goal of this study, patients must be
proficient in English or French Canadian.
• The patient must provide study-specific informed consent prior to study entry.
• Patients with impaired decision-making capacity are not permitted on study.
• ELIGIBILITY CRITERIA PRIOR TO STEP 2 REGISTRATION
• The following baseline neurocognitive tests must be completed within 21 days prior to
Step 2 registration: HVLT-R, TMT, and COWA. The neurocognitive test will be uploaded
into RAVE for evaluation by Dr. Wefel. Once the upload is complete, within 3 business
days a notification will be sent via email to the RA to proceed to Step 2.
• NOTE: Completed baseline neurocognitive tests can be uploaded at the time of Step
1 registration.
Exclusion Criteria:
• Planned infusion of cytotoxic chemotherapy on the same day as SRS or HA-WBRT
treatment. Patients may have had prior chemotherapy. Concurrent immunotherapy is
permitted.
• Prior allergic reaction to memantine.
• Intractable seizures while on adequate anticonvulsant therapy; more than 1 seizure per
month for the past 2 months.
• Patients with definitive leptomeningeal metastases.
• Known history of demyelinating disease such as multiple sclerosis.
• Contraindication to MR imaging such as implanted metal devices that are
MRI-incompatible, allergy to MRI contrast that cannot be adequately addressed with
pre-contrast medications, or foreign bodies that preclude MRI imaging. (Questions
regarding MRI compatibility of implanted objects should be reviewed with the Radiology
Department performing the MRI).
• Current use of (other N-methyl-D-aspartate [NMDA] antagonists) amantadine, ketamine,
or dextromethorphan.
• Radiographic evidence of hydrocephalus or other architectural change of the
ventricular system resulting in significant anatomic distortion of the hippocampus,
including placement of external ventricular drain or ventriculoperitoneal shunt.
• Mild cases of hydrocephalus not resulting in significant anatomic distortion of
the hippocampus are permitted.
• Prior radiotherapy to the brain, including SRS, WBRT, or prophylactic cranial
irradiation (PCI).
• Severe, active co-morbidity defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration
• Chronic obstructive pulmonary disease exacerbation or other acute respiratory
illness precluding study therapy at the time of registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
Metastatic Lung Small Cell Carcinoma, Metastatic Malignant Neoplasm in the Brain, Recurrent Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Lung
This study is being done to assess the safety of lopinavir/ritonavir in patients with PLWH
with AIN. 30 participants will be recruited and can expect to be on active study for
approximately 3 months and long term follow up for 40 weeks.
Evie Carchman, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05334004
Show full eligibility criteria
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Inclusion Criteria:
• willing to provide informed consent
• greater than or equal to 18 years of age
• Diagnosis of biopsy-confirmed HGAIN
• Human immunodeficiency virus (HIV)-positive with CD4 count greater than 200 cells/mm^3
at screening and virologically suppressed on HIV-1 antiretroviral therapy (ART) within
last 12 months
• willing to comply with all study procedures
Exclusion Criteria:
• Diagnosis of low-grade anal dysplasia (AIN, low-grade squamous intraepithelial lesion
(LSIL)) by HRA.
• CD4 count less than 200 cells/mm^3 at the time of consideration for entry into the
study
• unable to provide informed consent
• Pregnant or breastfeeding female
• Currently receiving systemic chemotherapy or radiation therapy for another cancer.
• Lipid profile abnormalities
• total cholesterol greater than 240 mg/dL
• low density lipoproteins (LDL) greater than 160 mg/dL
• high density lipoproteins (HDL) less than 40 mg/dL
• triglycerides greater than 500 mg/dL
• Have received topical therapy for anal dysplasia previously
• Participants who need to take drugs that are contraindicated with lopinavir/ritonavir
Phase 2 Basket Trial of Nab-sirolimus in Patients With Malignant Solid Tumors With Pathogenic Alterations in TSC1/TSC2 Genes (PRECISION 1)
A Phase 2 multi-center open-label basket trial of nab-sirolimus for adult and adolescent
patients with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or
TSC2 genes
Dustin Deming, MD
All
12 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05103358
Show full eligibility criteria
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Inclusion Criteria:
1. Patients must have a malignant solid tumor with a pathogenic inactivating TSC1 or TSC2
alteration. Genetic alterations should be identified using NGS in tumor tissue or
liquid biopsy).
• Patients will be enrolled after the central evaluation of NGS report confirms
eligibility.
2. Patients must have solid tumors that are metastatic or locally advanced where surgical
resection is not an option or likely to result in severe morbidity.
3. Patients must have received all standard therapies appropriate for their tumor type
and stage of disease or, in the opinion of the Investigator, the patient would be
unlikely to tolerate or derive clinically meaningful benefit from appropriate standard
of care therapy, or the patient has no satisfactory alternative treatments.
4. Patients must have 1 or more measurable target lesions by computed tomography (CT)
scan or magnetic resonance imaging (MRI) (RECIST v1.1).
5. Age: 12 years or older.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or Karnofsky
Performance Status (KPS) ≥80 or Lansky play-performance scale for pediatric patients
≥80.
7. Adequate liver function:
1. Total bilirubin ≤1.5 × upper limit of normal (ULN) (unless due to Gilbert's
syndrome, then ≤3 × ULN)
2. Aspartate aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if attributable to liver
metastases)
8. Adequate renal function: creatinine clearance ≥30 mL/min, Cockcroft-Gault CCr =
((140-age) × weight[kg]) / (72 × SCr[mL/min]) × 0.85, if female
9. Adequate hematologic parameters:
1. Absolute neutrophil count (ANC) ≥1.0 × 109/L (growth factor support allowed)
2. Platelet count ≥100,000/mm3 (100 × 109/L) (transfusion and/or growth factor
support allowed)
3. Hemoglobin ≥8.0 g/dL (transfusion and/or growth factor support allowed)
10. Fasting serum triglyceride must be ≤300 mg/dL; fasting serum cholesterol must be ≤350
mg/dL.
11. Minimum of 4 weeks since any major surgery, completion of radiation, or completion of
prior systemic anticancer therapy, or at least 5 half-lives if the prior therapy is a
single agent small-molecule therapeutic, and adequately recovered from the acute
toxicities of any prior therapy, including neuropathy, to Grade ≤1.
12. Male or non-pregnant and non-breastfeeding female:
1. Females of childbearing potential must agree to use effective contraception or
abstinence without interruption from 28 days prior to starting investigational
product (IP) throughout 3 months after last dose of IP and have a negative serum
pregnancy test (beta human chorionic gonadotropin, β-hCG) result at screening and
agree to ongoing pregnancy testing during the course of the study, and after the
end of study treatment. A second form of birth control is required even if she
has had a tubal ligation.
2. Male patients must agree not to donate sperm and must practice abstinence or
agree to use a condom during sexual contact with a pregnant female or a female of
childbearing potential while participating in the study and throughout 3 months
after last dose of IP. A second form of birth control is required even if he has
undergone a successful vasectomy.
13. The patient or the patient's parent(s) or legal guardian(s) understand(s) and sign(s)
the informed consent.
14. Willingness and ability to comply with scheduled visits, laboratory tests, and other
study procedures.
Exclusion Criteria:
1. Prior treatment with an mTOR inhibitor, including nab-sirolimus.
2. Severe (Grade ≥3) ongoing infection requiring parenteral or oral anti-infective
treatment, either ongoing or completed ≤7 days prior to enrollment.
3. Patients with primary brain tumors or PEComa.
4. Patients who have any severe and/or uncontrolled medical or psychiatric conditions or
other conditions that could affect their participation including:
1. Patients with meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal
cord compression, untreated brain metastases or symptomatic or unstable brain
metastases. Note: Patients with stable brain metastases (defined as asymptomatic
or no requirement for high-dose [defined as dexamethasone 10 mg daily or higher]
or increasing dose of systemic corticosteroids) and without imminent need of
radiation therapy are eligible. If applicable, patients must have completed brain
radiation therapy and recovered adequately from any associated toxicity and/or
complications prior to eligibility assessment. For patients who have received
prior radiation therapy, post-treatment MRI scan should show no increase in brain
lesion size/volume.
2. Unstable angina pectoris, symptomatic congestive heart failure (New York Heart
Association, NYHA class III or IV), myocardial infarction ≤6 months prior to
first study treatment, serious uncontrolled cardiac arrhythmia or any other
clinically significant cardiac disease.
3. Pre-existing severely impaired lung function. If a patient has a pre-existing
pulmonary condition, eligible patients should have a spirometry and diffusing
capacity for carbon monoxide (DLCO) that is >50% of the normal predicted value
and/or O2 saturation that is >88% at rest on room air (Note: spirometry and
pulmonary function tests [PFTs] not required to be performed unless clinically
indicated).
4. Nonmalignant medical illnesses that are uncontrolled or whose control may be
jeopardized by the treatment with the study therapy.
5. A history of malignancies other than the one under treatment unless the patient
is disease-free for more than 5 years from diagnosis. Note, controlled
non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental
prostate cancer, certain low grade hematologic malignancies (eg CLL, follicular
lymphoma, etc), or other adequately treated carcinoma-in-situ may be eligible,
after discussion with the medical monitor.
6. Uncontrolled hypertension (systolic blood pressure ≥160 mm-Hg and/or diastolic
blood pressure ≥100 mm Hg).
7. Patients with history of interstitial lung disease and/or pneumonitis, or
pulmonary hypertension.
8. Individuals with known human immunodeficiency virus (HIV) infection are excluded
from this study as combination antiretroviral therapy could potentially result in
significant pharmacokinetic interactions. In addition, these individuals are at
increased risk of serious infections due to the immunosuppressive effects of mTOR
inhibition.
9. Active Hepatitis B or Hepatitis C, with detectable viral load.
5. Regarding concomitant medications with significant CYP3A4 and P-gp interactions,
discontinuation of strong inhibitors (eg, ketoconazole, itraconazole, voriconazole,
erythromycin, clarithromycin, telithromycin, and others), strong inducers (eg,
rifampin, rifabutin), and known CYP3A4 substrates with a narrow therapeutic window
(eg, fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide,
quinidine, or terfenadine) is required at least 5 half lives prior to receiving the
first dose of nab-sirolimus, whichever is longer.
Tumor, Tumor, Solid, Metastasis, Metastatic Cancer, Cancer, Cancer Metastatic, Tumors, Neoplasms, Neoplasm Metastasis, Solid Tumor, Advanced Solid Tumor, Advanced Cancer, Malignant Solid Tumor, Malignant Solid Neoplasm, Malignant Neoplasm, Malignant Tumor, TSC, TSC1, TSC2, Metastatic Solid Tumor, Metastatic Neoplasm, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Lung, Melanoma/Skin cancer, Sarcoma, Uterus
AT GOAL: Adopting Technology for Glucose Optimization and Lifestyle in Pregnancy
This study will assess differences in patient preferences and glucose control between
continuous glucose monitoring and standard glucose checks in pregnant patients with Type 2
Diabetes. 40 participants will be on study for approximately 182 days (26 weeks).
Jacquelyn Adams
Female
18 Years to 45 Years old
N/A
This study is NOT accepting healthy volunteers
NCT05370612
Show full eligibility criteria
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Inclusion Criteria:
• Age greater than or equal to 18 years of age at enrollment
• Ability to consent in English
• Gestational age less than or equal to 19 weeks 6 days at enrollment
• Appropriate dating by certain LMP or ultrasound performed less than or equal to 19
weeks 6 day
• Diagnosis of Type 2 Diabetes less than or equal to 19 weeks 6 days
• Singleton gestation
Exclusion Criteria:
• Age less than 18 years of age at enrollment
• Lack of appropriate dating
• Multiple gestations
• Use of concentrated insulin at enrollment (ie U500)
• Preexisting CGM in place
• Chronic use of medications known to cause hyperglycemia, such as HIV antiretrovirals
and inhaled, injectable and oral corticosteroids
• Be unwilling or unable to present to Center for Perinatal Care for visits
The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study
This study aims to use clinical and biological characteristics of acute leukemias to screen
for patient eligibility for available pediatric leukemia sub-trials. Testing bone marrow and
blood from patients with leukemia that has come back after treatment or is difficult to treat
may provide information about the patient's leukemia that is important when deciding how to
best treat it, and may help doctors find better ways to diagnose and treat leukemia in
children, adolescents, and young adults.
Kenneth Desantes, M.D.
All
up to 22 Years old
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04726241
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Inclusion Criteria:
• Patients must be less than 22 years of age at the time of study enrollment
• Patient must have one of the following:
• Patient has known or suspected relapsed/refractory (including primary refractory)
AML
• This includes isolated myeloid sarcoma
• Patient has known or suspected relapsed/refractory (including primary refractory)
myeloid leukemia of Down syndrome
• Patient has known or suspected relapsed ALL that meets one of the following
criteria:
• Second or greater B-ALL medullary relapse, excluding KMT2Ar.
• Any first or greater B-ALL medullary relapse involving KMT2Ar.
• Any first or greater T-ALL medullary relapse with or without KMT2Ar.
• Patient has known or suspected relapsed/refractory (including primary refractory)
mixed phenotype acute leukemia (MPAL)
• Patient has known or suspected de novo or relapsed/refractory (including primary
refractory) treatment-related AML (t-AML) or treatment-related myelodysplastic
syndrome (t-MDS)
• Patient has known or suspected de novo or relapsed/refractory (including primary
refractory) myelodysplastic syndrome (MDS)
• Patient has known or suspected de novo or relapsed/refractory (including primary
refractory) juvenile myelomonocytic leukemia (JMML)
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Juvenile Myelomonocytic Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic Syndrome Post Cytotoxic Therapy, Myeloid Leukemia Associated With Down Syndrome, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Leukemia
Study of Ravulizumab in Pediatric Participants With HSCT-TMA
This study will evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of
ravulizumab administered by intravenous infusion to pediatric participants, from 1 month to <
18 years of age, with HSCT-TMA. The treatment period is 26 weeks, followed by a 26-week
off-treatment follow-up period.
Kenneth Desantes, M.D.
All
1 Month to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04557735
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Inclusion Criteria:
1. 1 month of age up to < 18 years of age at the time of signing the informed consent.
2. Received HSCT within the past 6 months.
3. Diagnosis of TMA that persists despite initial management of any triggering condition.
4. Body weight ≥ 5 kilograms.
5. Female participants of childbearing potential and male participants with female
partners of childbearing potential must use highly effective contraception starting at
Screening and continuing until at least 8 months after the last dose of ravulizumab.
6. Participants must be vaccinated against meningococcal infections if clinically
feasible, according to institutional guidelines for immune reconstitution after HSCT.
Participants must be re-vaccinated against Haemophilus influenzae type b and
Streptococcus pneumoniae if clinically feasible, according to institutional guidelines
for immune reconstitution after HSCT. All participants should be administered coverage
with prophylactic antibiotics according to institutional post-transplant infection
prophylaxis guidances, including coverage against Neisseria meningitidis for at least
2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal
vaccine should receive antibiotic prophylaxis coverage against Neisseria meningitidis
the entire Treatment Period and for 8 months following the final dose of ravulizumab.
Exclusion Criteria:
1. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin
type 1 motif, member 13' deficiency (activity < 5%).
2. Known Shiga toxin-related hemolytic uremic syndrome.
3. Positive direct Coombs test.
4. Diagnosis or suspicion of disseminated intravascular coagulation.
5. Known bone marrow/graft failure.
6. Diagnosis of veno-occlusive disease (VOD).
7. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody
titer).
8. Unresolved meningococcal disease.
9. Presence of sepsis requiring vasopressor support.
10. Pregnancy or breastfeeding.
11. Hypersensitivity to murine proteins or to 1 of the excipients of Ravulizumab.
12. Previously or currently treated with a complement inhibitor.
Thrombotic Microangiopathy, Other Hematopoietic, Hematologic cancers, other
In Vivo Metabolic Profiling of CLL (Chronic Lymphocytic Leukemia)
Metabolic reprogramming has been identified as a hallmark of cancer. Almost a century after
Otto Warburg initially discovered increased glycolytic activity in tumor tissue ("Warburg
effect"), therapeutic targeting of cancer metabolism has become a field of intense research
effort in cancer biology.
A growing appreciation of metabolic heterogeneity and complexity is currently reshaping
investigators "simplistic" understanding of metabolic reprogramming in cancer. Discovering
metabolic vulnerabilities as new treatment targets for cancer requires systematic dissection
of metabolic dependencies, fuel preferences, and underlying mechanisms in the specific
physiological context. However, today's data on cancer cell metabolic signatures and
heterogeneity in their physiological habitat of the human organism is sparse to non-existent
representing a critical knowledge gap in designing effective metabolic therapies. Here, the
investigators propose a "top-down" approach studying cancer cell metabolism in patients
followed by mechanistic in-depth studies in cell culture and animal models to define
metabolic vulnerabilities.
Investigators will develop a metabolic tracing method to quantitatively characterize
metabolic signatures and fuel preferences of leukemic lymphocytes in patients with chronic
lymphocytic leukemia (CLL). Isotopic metabolic tracers are nutrients that are chemically
identical to the native nutrient. Incorporated stable, non-radioactive isotopes allow
investigators to follow their metabolic fate by monitoring conversion of tracer nutrients
into downstream metabolites using cutting-edge metabolomics analysis. Using this method,
investigators propose to test the hypothesis that leukemic lymphocytes show tissue-specific
metabolic preferences that differ from non-leukemic lymphocytes and that ex vivo in-plasma
labeling represents a useful model for assaying metabolic activity in leukemic cells in a
patient-specific manner.
Christopher Fletcher, MD
All
18 Years and over
N/A
This study is also accepting healthy volunteers
NCT04785989
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Inclusion Criteria:
Group A
• Adult (18 years of age or older)
• No previous history of cancer
• Routine history of normal blood counts and vital signs
• Documented Informed Consent
Group B
• Adult (18 years of age or older)
• Diagnosis of CLL with low disease burden defined as Rai stage 0 ((Lymphocytosis; no
enlargement of the lymph nodes, spleen, or liver; red blood cell and platelet counts
are near normal.)
• Treatment naïve
• Documented Informed Consent
Group C
• Adult (18 years of age or older)
• Diagnosis of CLL with high systemic disease burden defined as infiltration of bone
marrow causing cytopenia
• Treatment naïve
• Able/willing to have bone marrow aspiration
• Documented Informed Consent
Exclusion Criteria:
For all participants
• Prisoners
• Psychiatric inpatients or people who are institutionalized
• Minor (Less than 18 years of age)
• History of diabetes
• Cannot be on antihyperglycemic therapy
• Carbohydrate restricting diets: Atkins, Vegan, Ketogenic, etc.
• Females of child bearing potential
• Persons without decision-making capacity
• Person who cannot read/write English
• Not meeting inclusion criteria defined above
Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016)
The purpose of this study is to determine the safety and efficacy of belzutifan in
combination with pembrolizumab and lenvatinib in multiple solid tumors including
hepatocellular carcinoma (HCC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma
(PDAC), biliary tract cancer (BTC), endometrial cancer (EC),and esophageal squamous cell
carcinoma (ESCC). There is no formal hypothesis testing in this study.
Nataliya Uboha, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04976634
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Inclusion Criteria:
• Diagnosis of one of the following advanced (unresectable and/or metastatic) solid
tumors, documented by histopathology or cytopathology:
• Hepatocellular carcinoma (HCC)
• Colorectal cancer (CRC) (non-microsatellite instability-high
[non-MSI-H]/deficient mismatch repair [dMMR])
• Pancreatic ductal adenocarcinoma (PDAC).
• Biliary tract cancer (BTC) (includes intrahepatic, extrahepatic
cholangiocarcinoma [CCA] and gall bladder cancer)
• Endometrial cancer (EC)
• Esophageal squamous cell carcinoma (ESCC)
• Disease progression on or since the most recent treatment (does not apply to newly
diagnosed unresectable or metastatic HCC or EC).
• Measurable disease per RECIST v1.1 as assessed locally (by investigator) and verified
by BICR
• Submission of an archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated
• Male participants are abstinent from heterosexual intercourse or agree to follow
contraceptive guidance during and for at least 7 days after last dose of study
intervention with belzutifan and lenvatinib
• Female participants are not pregnant or breastfeeding, not a woman of child-bearing
potential (WOCBP), or is a WOCBP and agrees to follow contraceptive guidance during
the intervention period and and for at least 120 days after the last dose of
pembrolizumab or for at least 30 days after last dose of lenvatinib or belzutifan,
whichever occurs last
• Adequate organ function
• Adequately controlled blood pressure with or without antihypertensive medications
• HCC Specific
Inclusion Criteria:
No prior systemic chemotherapy, including anti-VEGF
therapy, anti-programmed cell-death (PD-1)/PD-L1 or any systemic investigational
anticancer agents for advanced/unresectable HCC (1L)
• CRC ([non-MSI-H/dMMR) Specific
Inclusion Criteria:
Received at least 2 prior lines of
systemic therapy for unresectable or metastatic disease which includes
fluoropyrimidine, irinotecan and oxaliplatin
• PDAC Specific
Inclusion Criteria:
Prior therapy with at least 1 (platinum or
gemcitabine containing regimen) but no more than 2 prior systemic therapies for
unresectable or metastatic pancreatic cancer
• BTC Specific
Inclusion Criteria:
Received at least 1 prior line of systemic therapy
(containing gemcitabine or fluoropyrimidine) for unresectable or metastatic disease
• EC Specific
Inclusion Criteria:
Study treatment is for 1L therapy of EC and
participants should not have received prior systemic chemotherapy. Exception: May have
received 1 prior line of line of systemic platinum-based adjuvant and/or neoadjuvant
chemotherapy in the setting of a curative-intent resection, if the recurrence occurred
≥6 months after the last dose of chemotherapy or may have received prior radiation
with or without chemotherapy
• ESCC Specific
Inclusion Criteria:
Have experienced radiographic or clinical
progression on one prior line of standard systemic therapy (immune oncology (IO) naïve
participants) or an anti-PD-1/PD-L1 (IO resistant participants)
Exclusion Criteria:
• Unable to swallow orally administered medication or presence of a gastrointestinal
(GI) disorder that may affect study intervention absorption
• History of a second malignancy that is progressing or has required active treatment
within 3 years
• A pulse oximeter reading <92% at rest, or requirement of intermittent supplemental
oxygen/ chronic supplemental oxygen
• Presence of central nervous system (CNS) metastases and/or carcinomatous meningitis
• Clinically significant cardiovascular disease within 6 months of first dose of study
intervention
• Symptomatic pleural effusion, unless clinically stable after treatment
• Preexisting ≥ Grade 3 gastrointestinal (GI) or non-GI fistula
• Moderate to severe hepatic impairment
• Clinically significant history of bleeding within 3 months before screening
• Presence of serious active nonhealing wound/ulcer/bone fracture
• Requirement for hemodialysis or peritoneal dialysis
• History of human immunodeficiency virus (HIV) infection
• History of Hepatitis B or active Hepatis C virus infections. with exceptions for HCC
and BTC
• Prior therapy with a PD-1, anti-PD-L1, anti-PD-L2 agent, vascular endothelial growth
factor (VEGF) tyrosine kinase inhibitor (TKI) or hypoxia-inducible factor 2α (HIF-2α)
• Radiographic evidence of intratumoral cavitation, or invasion/infiltration of a major
blood vessel
• EC specific exclusion criteria: History of carcinosarcoma, endometrial leiomyosarcoma
or other high-grade sarcomas, or endometrial stromal sarcomas
• ESCC specific exclusion criteria: Has clinically apparent ascites or pleural effusion
or experienced weight loss >20% over approximately 3 months before first dose of study
therapy
COMbination Regimens in MM Post AHCT to elimiNate MRD Utilizing IbERdomide (COMMANDER)
Similar to the paradigm established in other hematologic malignancies that are considered
curable, the achievement of MRD(-) status is necessary for long term disease control in MM.
The fact that the majority of patients remain MRD (+) after induction therapy and AHCT points
to the opportunity to deploy novel agents with complementary mechanism of action and
favorable toxicity profile to reach and maintain MRD (-) status.
Given its favorable toxicity profile, the convenience of oral administration, and compelling
single agent activity even in heavily pretreated MM, iberdomide is likely amenable to long
term therapy in patients with high-risk of relapse/progression identified by the persistence
of MRD(+). The investigators intend to develop combination(s) of iberdomide with other agents
with complementary mechanism of action in the consolidation setting post AHCT in order to
achieve and sustain MRD (-).
Natalie Callander, MD
All
19 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05434689
Show full eligibility criteria
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Inclusion Criteria:
1. Age >18 years with no upper age limit
2. Confirmation of newly diagnosed multiple myeloma (MM) with 1-2 prior regimens utilized
in induction that included an immunomodulatory agent (IMiD) and a proteasome inhibitor
(PI) combined or in different regimens
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
4. Prior AHCT 100-180 days prior to initiation of protocol-directed therapy
5. MRD ≥ 10^-5 by clonoSEQ® NGS platform, determined 60-120 days after AHCT as part of
the usual care.
6. No prior disease progression (either before or since AHCT)
7. Overall response (i.e post-AHCT compared to historical baseline prior to initiation of
any therapy for MM) ≥ PR.
8. Measurable disease at the time of the initial diagnosis (i.e. prior to starting any
therapy for MM) meeting at least one of the following criteria:
• Serum monoclonal (M) protein ≥1.0 g/dl
• 200 mg of M protein/24h in the urine
• Difference between involved and uninvolved free light chain ≥10 mg/dL and
abnormal kappa to lambda ratio.
9. Adequate hepatic function evidenced by AST and ALT ≤ 3 x ULN and bilirubin ≤ 1.5 ULN.
10. Adequate bone marrow function evidenced by platelets ≥ 75,000 /mm3 (without
transfusion of platelets in the prior 7 days) and absolute neutrophil count ≥
1,000/mm3.
11. Creatinine clearance (CrCl) ≥ 40 mL/minute within 28 days prior to start of therapy
either measured or calculated using standard Cockcroft and Gault formula (available in
https://www.kidney.org/professionals/KDOQI/gfr_calculatorCoc ).
12. Females of childbearing potential (FCBP) must have two negative pregnancy tests as
verified by the investigator and agree to ongoing pregnancy testing and to practice
contraception during treatment. Male subjects must agree to practice contraception and
refrain from donating sperm during treatment.
13. In line with the higher incidence of MM in Blacks, and to address the historical
underrepresentation of ethnical minorities in MM trials, at least 25% of the enrolled
patients will be of ethnical minorities.
14. Written informed consent in accordance with federal, local, and institutional
guidelines.
Exclusion Criteria:
1. Diagnosis of amyloidosis, POEMS, Waldenstrom's macroglobulinemia, plasma cell leukemia
or smoldering multiple myeloma (i.e. never evolved to active myeloma).
2. Major surgery or radiotherapy within 28 days of starting protocol-directed treatment.
3. Acute active infection requiring treatment within 14 days of starting
protocol-directed treatment.
4. Current or prior involvement of central nervous system by multiple myeloma.
5. MM refractory to prior CD38 monoclonal antibody therapy and/or to carfilzomib (prior
exposure allowed). Refractoriness here is defined as not achieving at least a PR in a
regimen containing the agent or disease progression < 60 days from last dose of the
agent.
6. Pregnant or lactating females.
7. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg
negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or
antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time
polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels.
Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic
findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic
marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV
DNA by PCR.
8. Seropositive for hepatitis C (except in the setting of a sustained virologic response
[SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
9. Unstable angina or myocardial infarction within 4 months prior to starting
protocol-directed treatment, NYHA Class II, III or IV heart failure, uncontrolled
angina, history of severe coronary artery disease, severe uncontrolled ventricular
arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia
or Grade 3 conduction system abnormalities unless subject has a pacemaker.
10. A prolongation of QT interval on screening electrocardiogram (ECG) as defined by
corrected QT interval (QTc) > 480 ms using Fridericia's QT correction formula.
11. Cerebrovascular disease manifested as prior stroke at any time or TIA in the 12 months
prior to initiation of therapy.
12. Uncontrolled hypertension (per investigator assessment, despite optimal medical
management)
13. Diagnosis of interstitial lung disease
14. Nonhematologic malignancy within the past 3 years with the exception of a) adequately
treated basal cell carcinoma, squamous cell skin cancer, or localized thyroid cancer;
b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or
less with stable prostate-specific antigen levels; or d) cancer considered cured by
surgical resection or unlikely to impact survival during the duration of the study,
such as localized transitional cell carcinoma of the bladder or benign tumors of the
adrenal or pancreas.
15. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 28 days prior to
starting protocol-directed treatment.
16. For regimen B •Known history of allergy to Captisol® (a cyclodextrin derivative used
to solubilize carfilzomib).
17. Contra indication or intolerance to required supportive care medications (Aspirin and
Acyclovir)
18. Concomitant use of strong inhibitors or inducers of CYP3A4, P-gp, or BCRP, or BCRP
substrate with a narrow therapeutic index, for at least 14 days or 5 half-lives
(whichever is shorter). (consult
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interac
tions-table-substrates-inhibitors-and-inducers )
19. Any other clinically significant medical disease or condition that, in the
Investigator's opinion, may interfere with protocol adherence or a subject's ability
to give informed consent Diagnosis of amyloidosis, POEMS, Waldenstrom's
macroglobulinemia.
A Phase 2b Clinical Study With a Combination Immunotherapy in Newly Diagnosed Patients With Glioblastoma
The purpose of this study is to assess progression-free survival (PFS) and overall survival
(OS) in newly diagnosed Glioblastoma (GBM) participants treated with IGV-001 as compared with
placebo.
Ankush Bhatia, M.D.
All
18 Years to 70 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04485949
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Key
Inclusion Criteria:
• Has a Karnofsky performance scale (KPS) score ≥ 70 at screening
• Has a new diagnosis of GBM (WHO GRADE III or Grade IV GBM) based on the treating
neurosurgeon's best clinical judgement
• Has a diagnostic contrast-enhanced magnetic resonance imaging (MRI) scan with fluid
attenuated inversion-recovery (FLAIR) sequence of the brain at screening. Participants
must have a confirmed measurable disease pre-operatively with at least 1 lesion
measuring a total bi-perpendicular product of 4 centimeter square (cm^2) in 2
different planes (axial, sagittal, or coronal)
• The tumor must be located in the supratentorial compartment
• Has adequate bone marrow and organ function at screening
Key
Exclusion Criteria:
• Has bi-hemispheric disease, multicentric disease, or disease burden involving the
brain stem or cerebellum based on MRI post-gadolinium enhancement
• Has received any previous surgical resection or any anticancer intervention for glioma
• Has any history of glioma, a concurrent malignancy, or malignancy within 3 years of
randomization, unless definitive therapy is completed, with the exception of basal or
squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the
cervix or breast that has completed curative therapy
• Has any severe immunocompromised condition (eg, human immunodeficiency virus (HIV)
with a cluster of differentiation [CD] 4+ cell count <200*10^6/liter [L]) or any
active uncontrolled autoimmune disease (eg, Crohn's disease)
• Has an active cardiac disease or a history of cardiac dysfunction
• Is receiving any other investigational agent(s) or has received an investigational
agent within 30 days or 5 half-lives of investigational agent use, whichever is
longer, prior to screening
• Is partaking in another interventional study. Participants who are partaking in an
observational study are eligible
• Has received a live vaccine within 30 days of screening
• Has active and uncontrolled/untreated hepatitis B virus (HBV), hepatitis C virus
(HCV), HIV, or any other active infections that, in the Investigator's opinion, would
impair or prohibit a participant's participation in this study.
• Is receiving treatment with Tumor Treating Fields or Optune®
Brain and Nervous System, Brain/Central Nervous System, Glioblastoma
Combination Trial of Tipifarnib and Alpelisib in Adult Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)
This phase 1/2 combination trial of tipifarnib, a farnesyltransferase inhibitor, and
alpelisib, a PI3K inhibitor in participants with recurrent/metastatic head and neck squamous
cell carcinoma (HNSCC) whose tumors overexpress the HRAS protein and/or are PIK3CA-mutated
and/or PIK3CA-amplified.
Justine Bruce, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04997902
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Inclusion Criteria:
1. At least 18 years of age.
2. Histologically confirmed head and neck cancer of squamous histology not amenable to
local therapy with curative intent (surgery or radiation therapy with or without
chemotherapy).
3. Documented treatment failure from at least 1 prior systemic therapy in the R/M
setting, unless determined not appropriate.
4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
5. Has a tumor that is dependent upon HRAS and/or PIK3CA.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Acceptable liver, renal, endocrine, and hematologic function.
8. Must be able to swallow alpelisib whole tablet or oral suspension containing crushed
tablets. Feeding tube may not be used for alpelisib administration.
9. Other protocol defined inclusion criteria may apply.
Exclusion Criteria:
1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or
nonsquamous histologies (eg, mucosal melanoma).
2. Ongoing treatment with certain anticancer agents.
3. Prior treatment (at least 1 full treatment cycle) with an FTI or PI3K, mTOR, or AKT
inhibitor.
4. Received treatment for unstable angina, myocardial infarction, and/or cerebro-vascular
attack within the prior 6 months.
5. Non-tolerable Grade 2, or ≥ Grade 3 neuropathy or evidence of unstable neurological
symptoms within 4 weeks of Cycle 1 Day 1.
6. Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1,
without complete recovery.
7. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic
therapy.
8. Participant with an established diagnosis of diabetes mellitus Type 1 or not
controlled Type 2.
9. Participant has impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of the trial drugs based on Investigator
discretion.
10. Participant has currently documented pneumonitis/interstitial lung disease.
11. Participant has a history of severe cutaneous reaction, such as Stevens-Johnson
Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug
Reaction with Eosinophilia and Systemic Symptoms (DRESS).
12. Other protocol defined exclusion criteria may apply.
Lip, Oral Cavity and Pharynx, Head and Neck, HNSCC
Wide Field OCT + AI for Positive Margin Rates in Breast Conservation Surgery. (RCT)
This is a multi-center, randomized, two-arm study designed to measure the effectiveness of
the SELENE system in reducing the number of unaddressed positive margins in breast lumpectomy
procedures when used in addition to standard intraoperative margin assessment.
Lee Wilke, MD
Female
18 Years and over
N/A
This study is also accepting healthy volunteers
NCT05113927
Show full eligibility criteria
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Inclusion Criteria:
• Female
• Age 18 years or older
• Patients undergoing elective breast conservation surgery for the treatment of Stage
0-III invasive ductal and/or ductal carcinoma in situ
• May include subjects treated with neo-adjuvant therapy (endocrine and/or
chemotherapeutic), but not required for study inclusion
• Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
• Male
• Metastatic cancer (Stage IV)
• Lobular carcinoma as primary diagnosis
• Previous ipsilateral breast surgery for benign or malignant disease within two years
(this includes implants and breast augmentation)
• Subjects with multi-centric disease (histologically diagnosed cancer in two different
quadrants of the breast), unless resected in a single specimen
• Subjects with bilateral disease (diagnosed cancer in both breasts)
• Participating in any other investigational margin assessment study which can influence
collection of valid data under this study
• Use of cryo-assisted localization
• Currently lactating
• Current pregnancy
• Subjects for whom the specimen margins have been destroyed, damaged, or are otherwise
not intact prior to imaging (device arm only) imaging
Clarifying the Optimal Application of SLT Therapy Trial (COAST)
The goal of this study is to understand if SLT performed at low energy is as effective as SLT
performed at standard energy, and also to see if repeating SLT at low energy once a year will
prevent or delay the need for daily eye drop medications better than waiting for SLT to wear
off before repeating it.
Yao Liu
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT04967989
Show full eligibility criteria
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Inclusion Criteria:
1. Age 18 or older and in good health
2. Each eye with one of the following qualifying diagnoses (diagnoses may differ between
eyes):
1. High-risk ocular hypertension (OHT): IOP > 21 mmHg without glaucomatous optic
neuropathy (excavation, diffuse or focal thinning or notching of the neuroretinal
rim, visible nerve fiber layer defects, or asymmetry of the vertical cup-to-disc
ratio of >0.2 between eyes) [enrollment of trial participants with High-risk OHT
will be capped at 25% of total enrollment]
2. Mild primary open-angle glaucoma: glaucomatous optic neuropathy, visual field
mean deviation better than -6.0 dB with no points in the central 5° <15 dB (see
figure on next page)
3. Moderate primary open-angle glaucoma: glaucomatous optic neuropathy, visual field
mean deviation equal to or worse than -6.0 dB but no worse than -12.0 dB and no
central 5° points <15 dB or mean deviation -12.0 dB or better with 1 central 5°
points <15 dB (see figure on next page).
3. Each eye with BCVA 20/200 (UK 6/60) or better
Exclusion Criteria:
1. Use of topical IOP-lowering medications for more than 6 cumulative months at any time
in the past 5 years
2. Any history of IOP-lowering laser (prophylactic iridotomy not included) or surgical
procedure
3. Advanced POAG in either eye (worse than moderate POAG as defined above)
4. Glaucoma other than POAG (including pigmentary and pseudoexfoliation glaucoma) in
either eye
5. Mean IOP > 35 mmHg at either the screening or baseline visit in either eye
6. Narrow or closed angle (Shaffer Grade 0, 1, or 2) in either eye
7. Contraindications to SLT or any other study intervention
8. Any corneal pathology that would preclude accurate assessment of IOP by Goldmann
tonometry in either eye
9. Any intraocular surgical procedure within the past 6 months in either eye
10. Inability to attend all scheduled study visits
11. Pregnant or planning to become pregnant in the next 4 years
Glaucoma and Ocular Hypertension, Glaucoma, Other, Eye & Vision
A Phase 1b/2 Study of BGB-11417in Monotherapy and in Various Combinations With Dexamethasone and Carfilzomib in Multiple Myeloma
Study consists of two parts, a part 1 dose escalation and a part 2 cohort expansion in
combination with dexamethasone and carfilzomib intravenously across two cohorts with a
monotherapy component as well.
Natalie Callander, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04973605
Show full eligibility criteria
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Inclusion Criteria:
1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
2. A confirmed diagnosis of multiple myeloma (must have an M-component in serum and/or
urine)
3. Measurable disease defined as:
i. M-spike ≥ 500mg/dL, or ii. Urine protein M-spike of ≥ 200 mg/day, or iii. Serum
free light chains ≥ 10 mg/dL, and an abnormal κ:λ ratio
4. Participant has documented relapsed or progressive MM on or after any regimen or who
are refractory to the most recent line of therapy.
i. Relapsed MM is defined as previously treated MM that progresses and requires
initiation of salvage therapy but does not meet the criteria for refractory MM.
ii. Refractory MM is defined as disease that is nonresponsive (failure to achieve
minimal response or development of progressive disease) while on primary or salvage
therapy or progresses within 60 days of last therapy.
1. Participants in Part 1 should have failed all other available options including
having had ≥ 3 prior lines of therapy including a proteasome inhibitor, IMiD
agent, and an anti-CD38 monoclonal antibody.
2. Participants in Part 2 should have had and failed ≥ 1 but ≤ 7 prior lines of
therapy and will have had prior treatment with both a proteasome inhibitor and an
IMiD agent.
Note: A line of therapy consists of greater ≥ 1 complete cycle of a single agent,
a regimen consisting of combination of several drugs, or a planned sequential
therapy of various regimens. Induction therapy with consolidation and maintenance
following stem cell transplant is considered a single line of therapy.
3. Prior treatment with carfilzomib is allowed but the patient must not be
considered carfilzomib refractory and not have had carfilzomib within the past 6
months
5. Positivity for t(11;14) by validated fluorescence in situ hybridization (FISH) testing
assay in a pre-defined laboratory
a. fresh bone marrow aspirate sample must be collected at screening and sent to
central laboratory for t(11;14) FISH testing.
6. Adequate organ function defined as:
1. Hemoglobin ≥ 8.0 g/dL, within 7 days before first dose of study treatment,
independent of growth factor support and transfusions
2. Platelet count ≥ 75,000/μL, within 7 days before first dose of study treatment,
independent of growth factor support and transfusions
3. Absolute neutrophil count (ANC) ≥ 1000/mm3 [ANC = (% of segmented neutrophils + %
of segmented bands) x total WBC count within 7 days before first dose of study
treatment
4. ALT and AST ≤ 3 x upper limit of normal (ULN) and total bilirubin ≤ 2.0 x ULN
Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 45 mL/min/1.73 m2
calculated by the MDRD-6 formula.
Exclusion Criteria:
1. Participant has any of the following conditions:
1. Non secretory MM (Serum free light chains < 10 mg/dL)
2. Solitary plasmacytoma
3. Active plasma cell leukemia (ie, either 20% of peripheral white blood cells or >
2.0 x 109/L circulating plasma cells by standard differential)
4. Waldenström macroglobulinemia
5. Amyloidosis.
6. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes
(POEMS) syndrome
7. Uncontrolled diabetes (HbA1c > 7% or 53 mmol/mol or requiring insulin at study
entry
8. Chronic respiratory disease that requires continuous oxygen
2. Significant cardiovascular disease, including but not limited to:
1. Myocardial infarction ≤ 6 months before screening
2. Ejection fraction ≤ 50%
3. Unstable angina≤ 3 months before screening
4. New York Heart Association Class III or IV congestive heart failure
5. History of clinically significant arrhythmias (eg, sustained ventricular
tachycardia, ventricular fibrillation, or torsades de pointes)
6. Heart rate-corrected QT interval > 480 milliseconds based on Fridericia's formula
7. History of Mobitz II second-degree or third-degree heart block without a
permanent pacemaker in place
8. Uncontrolled hypertension at screening, defined as systolic blood pressure > 170
mmHg and diastolic blood pressure > 105 mmHg by ≥ 2 consecutive measurements
3. Known infection with human immunodeficiency virus (HIV)
4. Serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV)
infection as follows:
1. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(HBcAb). Participants with presence of HBcAb, but absence of HBsAg, are eligible
if HBV DNA is undetectable (limitation of sensitivity < 20 IU/mL) ,), and if they
are willing to undergo monthly monitoring for HBV reactivation.
2. Presence of HCV antibody. Participants with presence of HCV antibody are eligible
if HCV RNA is undetectable (limitation of sensitivity < 15 IU/mL).
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
This phase III trial compares the effect of open thoracic surgery (thoracotomy) to
thoracoscopic surgery (video-assisted thoracoscopic surgery or VATS) in treating patients
with osteosarcoma that has spread to the lung (pulmonary metastases). Open thoracic surgery
is a type of surgery done through a single larger incision (like a large cut) that goes
between the ribs, opens up the chest, and removes the cancer. Thoracoscopy is a type of chest
surgery where the doctor makes several small incisions and uses a small camera to help with
removing the cancer. This trial is being done evaluate the two different surgery methods for
patients with osteosarcoma that has spread to the lung to find out which is better.
Kenneth Desantes, M.D.
All
up to 50 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05235165
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Inclusion Criteria:
• Patients must be < 50 years at the time of enrollment.
• Patients must have =< 4 nodules per lung consistent with or suspicious for metastases,
with at least one of which being >= 3 mm and all of which must be =< 3 cm size.
• Note: Patient must have eligibility confirmed by rapid central imaging review.
• Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic
surgery. Determination of resectability is made by the institutional surgeon.
• Patients must have a histological diagnosis of osteosarcoma.
• Patients must have evidence of metastatic lung disease at the time of initial
diagnosis, or at time of 1st recurrence following completion of therapy for initially
localized disease.
• Patients with newly diagnosed disease must have completed successful gross tumor
resection for their primary tumor or surgical local control of primary tumor must be
planned to be performed simultaneously with thoracic surgery.
• Newly diagnosed patients must be receiving or recently completed (within 60 days)
systemic therapy considered by the treating physician to be standard treatment for
newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug
regimens) at the time of enrollment on this study. Dose and drug modifications for
toxicity do not exclude patients from participation.
• Patients at time of 1st recurrence must have completed systemic therapy for their
initial primary tumor, considered by the treating physician to be standard treatment
for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug
regimens) at the time of enrollment on this study. Dose and drug modifications for
toxicity do not exclude patients from participation.
Exclusion Criteria:
• Patients with unresectable primary tumor.
• Patients with pulmonary metastatic lesions that would require anatomic resection
(lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central
lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to
segmental bronchi).
• Patients with chest wall or mediastinal based metastatic lesions, or with significant
pleural effusion.
• Patients with disease progression at either the primary or pulmonary metastatic site
while on initial therapy. Note: Once the patient has been enrolled on the study,
additional computed tomography (CT) scans are not anticipated prior to thoracic
surgery. Note: Some variation in nodule size measurements over the course of
pre-operative therapy is anticipated and does not qualify for exclusion unless deemed
true disease progression by the primary treatment team.
• Patients with evidence of extrapulmonary metastatic disease.
• Patients who received therapeutic pulmonary surgery for lung metastasis prior to
enrollment.
• All patients and/or their parents or legal guardians must sign a written informed
consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met.
Metastatic Malignant Neoplasm in the Lung, Metastatic Osteosarcoma, Osteosarcoma, Bones and Joints, Sarcoma
A phase 3 randomized partial blind storage duration ranging study in patients undergoing
complex cardiac surgery that will compare the transfusion of cold stored platelets to
standard room temperature stored platelets. The primary objective is to establish that cold
stored platelets have a non-inferiority (or superiority) to room temperature platelets.
Eric Simon
All
0 Days to 84 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04834414
Show full eligibility criteria
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Inclusion Criteria:
• Viable neonates ≥ 3 kg at time of enrollment (as defined in Section 4.1) OR age
greater than 28 days and less than 85 years of age at time of consent; AND
• Planned complex cardiac surgery with planned use of cardiopulmonary bypass, with an
expectation of bleeding requiring platelet transfusion.
Exclusion Criteria:
• Expected order for washed or volume reduced platelets
• Patient with known anti-platelet antibodies
• Platelet transfusion refractoriness due to anti-HLA antibodies
• Known or suspected pregnancy
• Previously randomized in this study
• Conscious objection or unwillingness to receive blood products
• Known IgA deficiency
• Known congenital platelet disorder
• Known congenital bleeding disorder
• Planned post-operative extracorporeal membrane oxygenation (ECMO), ventricular assist
device (VAD), and/or continuous renal replacement therapy (CRRT)/ hemodialysis
• Patients intended to receive whole blood either intra-operative or post-operative for
bleeding
• Platelet transfusion (of any type) within 24 hours prior to the date of surgery
• Pre-operative thrombocytopenia, defined as platelet count <75x10(9)/L, based on the
most recent labs completed within 72 hours prior to the date of surgery.
Complications of heart transplant, Congenital malformation of heart, unspecified, Heart failure, Other acute ischemic heart diseases, Other, Heart & Vascular, Acute Blood Loss
Imaging and Genomic Biomarkers to Predict Response in Prostate Cancer
The purpose of this study is to evaluate the imaging and gene expression biomarkers in
prostate cancer. Participants have high-risk prostate cancer and have indicated they will
undergo external beam radiation therapy, brachytherapy, and androgen deprivation therapy
(EBRT+BTX+ADT). Participants can expect to be in this study for up to 5 years.
John Floberg, Assistant Professor
All
18 Years and over
Early Phase 1
This study is NOT accepting healthy volunteers
NCT05477823
Show full eligibility criteria
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Inclusion Criteria:
• Age ≥ 18
• Histologically confirmed adenocarcinoma of the prostate
• Cancer classified as high-risk or very high-risk by National Comprehensive Cancer
Network (NCCN) criteria: Grade group ≥4, PSA >20, or primary tumor stage ≥T3a
• ECOG performance status 0-1
• Agreed to undergo EBRT, high dose rate (HDR) brachytherapy boost, and 6-36 months of
ADT as part of standard of care therapy prior to study enrollment
• Able to undergo a HDR brachytherapy implant: Pre-radiation IPSS score ≤20 with or
without medical management; prostate ≤60 cc as measured by MRI or ultrasound; no prior
trans-urethral resection of prostate (TURP); and, median lobe extending into the
bladder <1 cm
• No prior or concurrent malignancy unless disease-free for at least 5 years
Exclusion Criteria:
• Evidence of regional or distant metastatic disease on pre-treatment bone scan, pelvic
MRI, and/or CT of the abdomen/pelvis
• Prior pelvic radiation therapy
The Acute Burn ResUscitation Multicenter Prospective Trial (ABRUPT2)
This is a prospective randomized multi-center study which will compare acute fluid
resuscitation using a colloid strategy (LR + 5% Albumin) to a crystalloid strategy (LR
alone), in adults with an acute burn involving at least 25% of their total body surface area.
Angela Gibson
All
18 Years and over
N/A
This study is NOT accepting healthy volunteers
NCT04356859
Show full eligibility criteria
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Inclusion Criteria:
• Age ≥ 18 years
• Total burn size (second and third degree) is ≥ 25% of the TBSA
• Burn center admission within 12 hours of injury.
• There is a plan for formal fluid resuscitation.
Exclusion Criteria:
• Significant associated trauma
• High voltage (≥ 1000 volts) electrical burns
• Burn wound excision surgery within 48 hours from injury
• Fresh frozen plasma (FFP) given at any time ≤ 48 hours from injury
• Hypertonic saline (HTS) given at any time ≤ 48 hours from injury
• Hydroxyethyl starch (HES) given at any time ≤ 48 hours from injury
• High dose Vitamin C infusion given at any time ≤ 48 hours from injury
• Administration of human albumin prior to randomization
• Palliative comfort measures are instituted ≤ 48 hours from injury
• Pregnancy
• Pre-injury chronic renal insufficiency equal to or greater than stage 3
• Pre-injury chronic hepatic disease (Child-Pugh B or C)
• Pre-injury left ventricular (LV) dysfunction (echocardiography LV grade II-IV or
ejection fraction ≤ 35%)
Burn Injury, Burn of unspecified body region, unspecified degree, Other, Injury, Trauma & Emergency Medicine, Skin & Dermatology
Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score
This phase III trial uses the Decipher risk score to guide intensification (for higher
Decipher gene risk) or de-intensification (for low Decipher gene risk) of treatment to better
match therapies to an individual patient's cancer aggressiveness. The Decipher risk score
evaluates a prostate cancer tumor for its potential for spreading. In patients with low risk
scores, this trial compares radiation therapy alone to the usual treatment of radiation
therapy and hormone therapy (androgen deprivation therapy). Radiation therapy uses high
energy x-rays or particles to kill tumor cells and shrink tumors. Androgen deprivation
therapy blocks the production or interferes with the action of male sex hormones such as
testosterone, which plays a role in prostate cancer development. Giving radiation treatment
alone may be the same as the usual approach in controlling the cancer and preventing it from
spreading, while avoiding the side effects associated with hormonal therapy. In patients with
higher Decipher gene risk, this trial compares the addition of darolutamide to usual
treatment radiation therapy and hormone therapy, to usual treatment. Darolutamide blocks the
actions of the androgens (e.g. testosterone) in the tumor cells and in the body. The addition
of darolutamide to the usual treatment may better control the cancer and prevent it from
spreading.
John Floberg, Assistant Professor
Male
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05050084
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of
the prostate within 270 days prior to registration
• Unfavorable intermediate risk prostate cancer, defined as having ALL the following
bulleted criteria:
• Has at least one intermediate risk factor (IRF):
• PSA 10-20 ng/mL
• Clinical stage T2b-c (digital rectal examination [DRE] and/or imaging) by
American Joint Committee on Cancer (AJCC) 8th edition
• Gleason score 7 (Gleason 3+4 or 4+3 [ International Society of Urological
Pathology (ISUP) Grade Group 2-3])
• Has ONE or more of the following 'unfavorable' intermediate-risk designators:
• > 1 immature reticulocyte fraction (IRF)
• Gleason 4+3=7 (ISUP Grade Group 3)
• >= 50% of biopsy cores positive
• Biopsies may include 'sextant' sampling of right/left regions of the
prostate, often labeled base, mid-gland and apex. All such 'sextant'
biopsy cores should be counted. Men may also undergo 'targeted'
sampling of prostate lesions (guided by MRI, ultrasound or other
approaches). A targeted lesion that is biopsied more than once and
demonstrates cancer (regardless of number of targeted cores involved)
should count as a single additional positive core sampled and positive.
In cases of uncertainty, count the biopsy sampling as sextant core(s)
• Absence of high-risk features
• Appropriate stage for study entry based on the following diagnostic workup:
• History/physical examination within 120 days prior to registration;
• Negative bone imaging (M0) within 120 days prior to registration; Note: Tc-99m
bone scan or sodium fluoride (NaF) positron emission tomography (PET) are
allowed. Equivocal bone scan findings are allowed if plain films X-ray, computed
tomography (CT) or magnetic resonance imaging (MRI) are negative for metastasis
at the concerned site(s). While a negative fluciclovine, choline, or prostate
specific membrane antigen (PSMA) PET may be counted as acceptable substitute for
bone imaging, any suspicious findings must be confirmed and correlated with
conventional imaging (Tc-99m bone scan, NaF PET, CT, X-ray, or MRI) to determine
eligibility based on the latter modalities (e.g. M0 based on conventional imaging
modalities)
• Clinically negative lymph nodes (N0) as established by conventional imaging
(pelvic +/- abdominal CT or MR), within 120 days prior to registration. Patients
with lymph nodes equivocal or questionable by imaging are eligible if the nodes
are =< 1.0 cm in short axis and/or if biopsy is negative.
Note: While a negative fluciclovine, choline, or prostate specific membrane antigen (PSMA)
PET may be counted as acceptable substitute for pelvic imaging, any suspicious findings
must be confirmed by conventional imaging (CT, MRI or biopsy). If the findings do not meet
pathological criteria based on the latter modalities (e.g. node =< 10 mm in short axis,
negative biopsy), the patient will still be eligible
• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 120 days
prior to registration
• Non-castrate testosterone level (> 50 ng/dL) within 120 days prior to registration
• Absolute neutrophil >= 1,000 cells/mm^3 (within 120 days prior to registration)
• Hemoglobin >= 8.0 g/dL, independent of transfusion and/or growth factors (within 120
days prior to registration)
• Platelet count >= 100,000 cells/mm^3 independent of transfusion and/or growth factors
(within 120 days prior to registration)
• Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault equation (within
120 days prior to registration)
• For African American patients specifically whose renal function is not considered
adequate by the formula above, an alternative formula that takes race into
account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula)
should be used for calculating the related estimated glomerular filtration rate
(GFR) with a correction factor for African American race creatinine clearance for
trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
• Total bilirubin: 1.5 =< institutional upper limit of normal (ULN) (within 120 days
prior to registration) (Note: In subjects with Gilbert's syndrome, if total bilirubin
is > 1.5 x ULN, measure direct and indirect bilirubin. If direct bilirubin is less
than or equal to 1.5 x ULN, subject is eligible)
• Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]): =< 2.5 x
institutional ULN (within 120 days prior to registration)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial;
Note: HIV testing is not required for eligibility for this protocol
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated.
• Note: Known positive test for hepatitis B virus surface antigen (HBV sAg)
indicating acute or chronic infection would make the patient ineligible unless
the viral load becomes undetectable on suppressive therapy. Patients who are
immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible
(e.g. patients immunized against hepatitis B)
• For patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on treatment,
they are eligible if they have an undetectable HCV viral load
• Note: Known positive test for hepatitis C virus ribonucleic acid (HCV RNA)
indicating acute or chronic infection would make the patient ineligible unless
the viral load becomes undetectable on suppressive therapy
• The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry and, for patients treated in the United States
(U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Previous radical surgery (prostatectomy) or any form of curative-intent ablation
whether focal or whole-gland (e.g., cryosurgery, high intensity focused ultrasound
[HIFU], laser thermal ablation, etc.) for prostate cancer
• Definitive clinical or radiologic evidence of metastatic disease (M1)
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 3 years. History of or current diagnosis of hematologic malignancy is
not allowed
• Prior radiotherapy to the prostate/pelvis region that would result in overlap of
radiation therapy fields
• Previous bilateral orchiectomy
• Previous hormonal therapy, such as luteinizing hormone-releasing hormone (LHRH)
agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist
(e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate).
ADT started prior to study registration is not allowed
• Prior use of 5-alpha-reductase inhibitors is allowed, however, it must be stopped
prior to enrollment on the study with at least a 30 day washout period before baseline
study PSA measure and registration
• Active testosterone replacement therapy; any replacement therapy must be stopped at
least 30 days prior to registration
• Severe, active co-morbidity defined as follows:
• Current severe or unstable angina;
• New York Heart Association Functional Classification III/IV (Note: Patients with
known history or current symptoms of cardiac disease, or history of treatment
with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification)
• History of any condition that in the opinion of the investigator, would preclude
participation in this study
• Inability to swallow oral pills
• High risk features, which includes any of the following:
• Gleason 8-10 [ISUP Grade Group 4-5]
• PSA > 20
• cT3-4 by digital exam OR gross extra-prostatic extension on imaging
[indeterminate MRI evidence will not count and the patient will be eligible]
A Study to See if Memantine Protects the Brain During Radiation Therapy Treatment for Primary Central Nervous System Tumors
This phase III trial compares memantine to usual treatment in treating patients with primary
central nervous system tumors. Memantine may block receptors (parts of nerve cells) in the
brain known to contribute to a decline in cognitive function. Giving memantine may make a
difference in cognitive function (attention, memory, or other thought processes) in children
and adolescents receiving brain radiation therapy to treat a primary central nervous system
tumors.
Kenneth Desantes, M.D.
All
4 Years to 17 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT04939597
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Inclusion Criteria:
• >= 4 and < 18 years at time of study entry
• Patients must weigh 15 kg or greater at time of study entry
• Primary central nervous system tumors that have not received prior cranial
radiotherapy
• Planned focal, cranial or craniospinal radiation treatment for a primary central
nervous system tumor
• The patient must have receptive and expressive language skills in English, French or
Spanish since the neurocognitive function and quality of life (QOL) assessment
instruments are available in these languages only
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 4 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 male; 0.8 female
• Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 male; 1 female
• Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 male; 1.2 female
• Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 male; 1.4 female
• Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 male; 1.4 female
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
U/L
• Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the
value of 45 U/L
• The patient must be able to undergo magnetic resonance imaging
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met
Exclusion Criteria:
• Life expectancy of less than 18 months
• Pre-existing conditions:
• Any contraindication or allergy to study drug (memantine or placebo)
• Intractable seizures while on adequate anticonvulsant therapy, defined as more
than one seizure per month for the past 2 months or since initiating
anticonvulsant therapy
• History of neurodevelopmental disorder such as Down syndrome, Fragile X,
William's Syndrome, intellectual disability (presumed intelligence quotient [IQ]
< 70), etc
• Co-morbid systemic illnesses, psychiatric conditions, social situations, or other
severe concurrent disease which, in the judgment of the investigator, would make
the patient inappropriate for entry into this study or interfere significantly
with the proper assessment of safety and toxicity of the prescribed regimens or
would limit compliance with the study requirements
• Patients with a motor, visual, or auditory condition that precludes participation
in computerized neurocognitive assessments
• Patients with any medical condition or taking medications that lead to
alterations of urine pH towards the alkaline condition (e.g., renal tubular
acidosis, carbonic anhydrase inhibitors, sodium bicarbonate)
• Personal history of prior cranial or craniospinal radiotherapy is not allowed
• Note: Prior anti-cancer therapy including surgery, chemotherapy, targeted agents
are allowed as per standard of care clinical treatment guidelines
• Female patients who are pregnant are excluded since fetal toxicities and teratogenic
effects have been noted for the study drug. A pregnancy test is required for female
patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who do not agree to use an
effective contraceptive method for the duration of their study participation
Central Nervous System Carcinoma, Brain and Nervous System, Brain/Central Nervous System
Phase 2b Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-uveitis
Izokibep is a small protein molecule that acts as a selective, potent inhibitor of
interleukin-17A, to which it binds with high affinity. This study investigates izokibep in
subjects with active non-infectious, intermediate-, posterior- or pan-uveitis requiring
high-dose steroids.
Laura Kopplin
All
18 Years to 75 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT05384249
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Inclusion Criteria:
General
• Subject has provided signed informed consent including consenting to comply with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol.
• 18 years to 75 years of age
Type of Subject and Disease Characteristics
• Subject is diagnosed with non-infectious intermediate-, posterior- or pan-uveitis
• Active disease defined by the presence of at least 1 of the following criteria in at
least 1 eye despite treatment with stable doses of corticosteroids for at least 2
weeks prior to day 1:
• Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion
by dilated indirect ophthalmoscopy, fundus photography, fluorescein angiography
(FA), and Spectral-Domain Optical Coherence Tomography (SD-OCT) to determine
whether a lesion is active or inactive (the central reading center assessment
using FA, fundus photography and/or SD-OCT is required to confirm eligibility
prior to day 1).
• ≥ 2+ vitreous haze (National Eye Institute [NEI]/Standardization of Uveitis
Nomenclature [SUN] criteria) by digital indirect ophthalmoscope and fundus
photography (the central reading center assessment using fundus photography is
required to confirm eligibility prior to day 1).
• Currently receiving treatment with oral corticosteroids (≥ 7.5 mg/day to ≤ 40 mg/day
oral prednisone/prednisolone or corticosteroid equivalent) at a stable dose for at
least 2 weeks prior to day 1.
Exclusion Criteria:
Disease-related Medical Conditions
• Subject with isolated anterior uveitis
• Subject with serpiginous choroidopathy
• Subject with confirmed or suspected infectious uveitis
• Subject with corneal or lens opacity that precludes visualization of the fundus or
that likely requires cataract surgery during the duration of the study
• Subject with intraocular pressure of ≥ 25 mmHg while on ≥ 2 glaucoma medications or
evidence of glaucomatous optic nerve injury
• Subject with severe vitreous haze that precludes visualization of the fundus prior to
first dose of study drug
• Subject has a contraindication for mydriatic eye drops OR subject cannot be dilated
sufficiently well to permit good fundus visualization
• Subject with best corrected visual acuity (BCVA) < 20 letters (Early Treatment
Diabetic Retinopathy Study [ETDRS]) in at least 1 eye prior to first dose of study
drug
• Subject with proliferative or severe non-proliferative retinopathy or clinically
significant macular edema due to diabetic retinopathy
• Subject with neovascular/wet age-related macular degeneration
• Subject with an abnormality of the vitreo-retinal interface with the potential for
macular structural damage independent of the inflammatory process
• Subject with a history of active scleritis ≤ 12 months of first dose of study drug
Other protocol defined Inclusion/Exclusion criteria may apply
Temozolomide and Atezolizumab as Second or Third Line for the Treatment of Metastatic or Recurrent Small Cell Lung Cancer
This phase II trial studies the effects of temozolomide and atezolizumab as second or third
line treatment for patients with small cell lung cancer that has spread to other places in
the body (metastatic) or has come back (recurrent). Chemotherapy drugs, such as temozolomide,
work in different ways to stop the growth of tumor cells, either by killing the cells, by
stopping them from dividing, or by stopping them from spreading. Immunotherapy with
monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the
cancer, and may interfere with the ability of tumor cells to grow and spread. Giving
temozolomide and atezolizumab as second or third line treatment may help prolong survival in
patients with small cell lung cancer.
Vincent Ma, MD
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT04919382
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Inclusion Criteria:
• Written informed consent and Health Insurance Portability and Accountability Act
(HIPAA) authorization for release of personal health information
• NOTE: HIPAA authorization may be included in the informed consent or obtained
separately
• Age >= 18 years at the time of consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 days
prior to registration
• Have histologically or cytologically-documented diagnosis of extensive stage (i.e.
metastatic and/or recurrent) small cell lung cancer and have progressed or recurred
after platinum-based chemotherapy with immunotherapy. Eligible patients will be
defined as follows:
• "Sensitive" Disease: Patients who had one previous line of chemotherapy and
relapsed after > 90 days of completion of treatment
• "Resistant" Disease: Patients with no response to first-line chemo-immunotherapy
or progression < 90 days after completing treatment
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1 within 28 days prior to registration
• Maximum of 2 prior lines of systemic therapy is allowed in the setting of metastatic
disease. Patients who recur after treatment for limited state disease, and who receive
first line metastatic treatment with chemo-immunotherapy would be considered eligible
upon progression on chemo-IO in the metastatic setting
• Absolute neutrophil count (ANC) >= 1.5 K/mm^3 (obtained within 28 days prior to
registration)
• Platelets >= 100,000 / mcL (obtained within 28 days prior to registration)
• Serum creatinine =< 2.0 X upper limit of normal (ULN) OR measured or calculated
creatinine clearance (glomerular filtration rate [GFR] can also be used in place of
creatinine or creatinine clearance [CrCl]) >= 50 mL/min as estimated by Cockcroft and
Gault formula for subject with creatinine levels > 2 x institutional ULN (obtained
within 28 days prior to registration)
• Bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin
levels > 1.5 ULN
• Patients with known Gilbert disease: serum bilirubin =< 3 x ULN) (obtained within
28 days prior to registration)
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) =< 3 X ULN OR =< 5
X ULN for subjects with liver metastases (obtained within 28 days prior to
registration)
• Albumin > 2.5 g/dL (obtained within 28 days prior to registration)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN for
patients not receiving therapeutic anticoagulation (obtained within 28 days prior to
registration)
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Activated partial thromboplastin time (aPTT) =< 1.5 x ULN for patients not receiving
therapeutic anticoagulation (obtained within 28 days prior to registration)
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Females of childbearing potential must have a negative serum or urine pregnancy test
within 14 days prior to registration
• For women of childbearing potential: agreement to remain abstinent (refrain from
vaginal intercourse) or use contraceptive methods and agreement to refrain from
donating eggs, as defined below:
• Women must remain abstinent or use contraceptive methods with a failure rate of <
1% per year during the treatment period and for 5 months after the final dose of
atezolizumab or temozolomide. Women must refrain from donating eggs during this
same period
• Examples of contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, hormonal contraceptives that
inhibit ovulation, hormone releasing intrauterine devices, and copper
intrauterine devices
• The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, or post
ovulation methods) and withdrawal are not adequate methods of contraception
• For men able to father a child: agreement to remain abstinent (refrain from vaginal
intercourse) or use a condom, and agreement to refrain from donating sperm, as defined
below:
• With a female partner of childbearing potential or pregnant female partner, men
must remain abstinent or use a condom during the treatment period and for 3
months after the final dose of temozolomide to avoid exposing the embryo. Men
must refrain from donating sperm during this same period
• The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not adequate methods of contraception
• As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study
• Availability of archival tissue, preferably a recent formalin-fixed, paraffin-embedded
(FFPE) tumor tissue block. A recently obtained archival FFPE tumor tissue block from a
primary or metastatic tumor resection or biopsy can be provided if it was obtained
within 1 year of trial screening. Patients with tumor specimens older than 1 year may
still be eligible if deemed so by study sponsor. For eligibility, only confirmation of
archival tissue is needed. Verification of tumor burden in the biopsy is encouraged.
For optimal biomarker results, tumor content should be > 30% of total tissue area
• Be willing to provide peripheral blood samples at specified time-points during the
study
• Life expectancy greater than 3 months as determined by the enrolling physician or
protocol designee
• Ability to swallow and retain oral medication
Exclusion Criteria:
• Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment
• Has received prior temozolomide therapy
• Patients with a prior or concurrent malignancy whose natural history or treatment has
the potential to interfere with the safety or efficacy assessment of the
investigational regimen are not eligible for this trial
• Symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
Subjects with asymptomatic lesions will be eligible if considered appropriate by the
treating physician
• NOTE: Subjects who are symptomatic and have not undergone prior brain imaging
must undergo a head computed tomography (CT) scan or brain MRI within 28 days
prior to registration to exclude brain metastases
• NOTE: A subject with prior brain metastasis may be considered if they have
completed their treatment for brain metastasis at least 2 weeks prior to study
registration, have been off corticosteroids for ≥ 2 weeks, and are asymptomatic
• Clinically significant acute infection requiring systemic antibacterial, antifungal,
or antiviral therapy including:
• Tuberculosis (clinical evaluation that includes clinical history, physical
examination, and radiographic findings, and TB testing in line with local
practice)
• Hepatitis B (known positive HBV surface antigen [HBsAg] result)
• Hepatitis C, or
• Human immunodeficiency virus (positive HIV 1/2 antibodies)
• NOTES: Patients with a past or resolved HBV infection (defined as the presence of
hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. In
patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated. Patients
positive for hepatitis C (HCV) antibody are eligible only if polymerase chain
reaction is negative for HCV ribonucleic acid (RNA). Subjects with HIV/acquired
immunodeficiency syndrome (AIDS) with adequate antiviral therapy to control viral
load (i.e undetectable) would be allowed if they are stable and have been on
treatment for >= 4 weeks prior to first dose of study drug(s). Subjects with
viral hepatitis with controlled viral load would be allowed while on suppressive
antiviral therapy. Testing not required
• Has had prior chemotherapy, immunotherapy, targeted small molecule therapy, or
radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e.,
=< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: Subjects with =< grade 2 neuropathy or alopecia due to chemotherapy are an
exception to this criterion and may qualify for the study
• Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting therapy
• Note: Subjects with irreversible toxicity that in the opinion of the treating
physician is not reasonably expected to be exacerbated by the investigational
product may be included (e.g., hearing loss, hormone deficiency requiring
replacement therapy)
• Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome,
or multiple sclerosis, with the following exceptions:
• Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not
considered a form of systemic treatment
• Patients with controlled type 1 diabetes mellitus who are on an insulin regimen
are eligible for the study
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis are
excluded) are eligible for the study provided all of following conditions are
met:
• Rash must cover =< 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical
corticosteroids
• No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic
agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids
within the previous 12 months
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan. History of
radiation pneumonitis in the radiation field (fibrosis) is permitted
• Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3
months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
treatment
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study)
• Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of
the atezolizumab formulation
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (more than once monthly). Patients with indwelling catheters
(e.g., PleurX) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium >12
mg/dL or corrected serum calcium > ULN)
• History of leptomeningeal disease
Extensive Stage Lung Small Cell Carcinoma, Metastatic Lung Small Cell Carcinoma, Recurrent Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8, Lung
COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study (CPAT-SG)
An open label, non-randomized pilot study in kidney transplant recipients who received a
completed primary series and bivalent booster of mRNA based COVID-19 vaccine and have =<2500
U/mL SARS-CoV-2 S antibody concentration using the Roche Elecsys(R) anti-RBD assay. Up to 80
participants will be enrolled in this study. Eligible participants will receive a dose of the
Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine candidate..
The primary objective is to determine whether a booster dose of the Sanofi-GSK monovalent
(B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine will elicit an increased SARS-CoV-2 antibody
response in participants who have failed to maintain an antibody titer >2500 U/mL (using the
Roche Elecsys(R) anti-RBD assay) to 2 or more doses of mRNA based COVID-19 vaccine
Jacqueline Garonzik Wang
All
18 Years and over
Phase 2
This study is NOT accepting healthy volunteers
NCT05518487
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Inclusion Criteria:
1. Able to understand and provide informed consent
2. Individual ≥ 18 years of age.
3. Recipient of kidney transplant >=12 months prior to enrollment, without treated
allograft rejection in the 6 months preceding enrollment
4. Maintenance immunosuppressive regimen consisting of CNI and mycophenolate mofetil or
mycophenolate, with or without <= 5mg/day prednisone or equivalent
5. Received completed primary series (3 doses) of mRNA vaccine (either the Moderna
COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine) as specified in the respective
package inserts
6. Receipt a COVID-19 bivalent mRNA booster (Moderna or Pfizer-BioNTech) >30 days prior
to enrollment.
7. Serum antibody titer up to 2500 U/mL at >=30 days from the last dose of mRNA COVID-19
vaccine and =>30 days following receipt of a monoclonal antibody product or
convalescent plasma for COVID-19, measured using the Roche Elecsys(R) anti-SARS-CoV-2
S assay
8. Platelet count greater than 30,000/cu mm must be confirmed in participants with a
known history of bleeding disorder or thrombocytopenia (platelet count <50,000/cu mm)
9. A female participant is eligible to participate if she is not pregnant or
breastfeeding and one of the following conditions applies:
1. Is of non-childbearing potential. To be considered of non-childbearing potential,
a female must be post-menopausal for at least 1 year or surgically sterile
OR
2. Is of childbearing potential and agrees to use an effective contraceptive method
or abstinence for 12 weeks post vaccine and while taking mycophenolate
mofetil/mycophenolic acid
Exclusion Criteria:
1. Recipient of any number of doses of any COVID vaccine product other than the Moderna
COVID-19 vaccine or the Pfizer-BioNTech COVID-19 vaccine
2. Recipient of any organ other than a kidney
3. Known current or prior Donor Specific Antibody (DSA)
4. Any change in transplant immunosuppression regimen (drug or dose) in response to
suspected or proven rejection within the last 6 months
5. Known diagnosis of COVID-19 since last antibody test
6. Receipt of a monoclonal antibody product or convalescent plasma within the last 30
days
7. Known history of hypersensitivity to any of the vaccine components, or history of a
life-threatening reaction to a vaccine containing any of the same substances.
(components listed in Section 6, and the CoV2 and AS03 Investigator's Brochure)
8. Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding
inclusion, contraindicating intramuscular (IM) vaccination based on Investigator's
judgment
9. Moderate or severe acute illness/infection (according to investigator judgment) on the
day of vaccination or febrile illness (temperature >=38.0°C [>=100.4°F]). A
prospective participant should not be included in the study until the condition has
resolved or the febrile event has subsided
10. Receipt of any vaccine in the 30 days preceding the study vaccine or planned vaccines
in the 30 days following the study vaccine
11. Estimated Glomerular Filtration Rate <30mL/min/1.73m^2
12. Receipt of any cellular depleting agent (e.g. Antithymocyte globulin (ATG), Rituximab,
Alemtuzumab, Cyclophosphamide) within 12 months preceding enrollment
13. Receiving systemic immunomodulatory medication(s) for any condition other than
transplant
14. Any uncontrolled active infection
15. Infection with human immunodeficiency virus (HIV)
16. Maintenance immunosuppressive regimen that includes anything other than a CNI,
mycophenolate/mycophenolate mofetil, and =< 5mg/day prednisone or equivalent
17. Recent (within one year) or ongoing treatment for malignancy, except for definitive
surgical treatment of localized skin cancers
18. Any unstable acute or chronic illness, treatments, or findings which, in the opinion
of the investigator, may pose additional risks from participation in the study, may
interfere with the c candidate's ability to comply with study requirements or may
impact the quality or interpretation of the data obtained from the study
COVID-19, Kidney Transplant, Kidney replaced by transplant, Other, Transplant
The study objective for the Phase 2 of this research is to demonstrate and confirm the
substantial time savings that can be obtained using cone beam computed tomography (CB-CT) for
both complete image acquisition and rapid image reconstruction in a Direct to Angio paradigm
(One Stop Shop) for selected acute ischemic stroke (AIS) patients.
Beverly Aagaard
All
18 Years to 99 Years old
N/A
This study is NOT accepting healthy volunteers
NCT05536895
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Inclusion Criteria:
1. Patients with acute ischemic stroke presenting within 24 hours of onset
2. Patients that present with a large artery occlusion
3. Adults 18 years of age or older.
4. Patients of childbearing potential must not be pregnant.
5. National Institutes of Health Stroke Scale (NIHSS) of <8
6. No severe co-morbidities
Exclusion Criteria:
1. Patients that are pregnant
2. History of severe renal disease (e.g. stage 4-5)
3. History of renal transplant
Oral N-acetylcysteine for Retinitis Pigmentosa (NAC Attack)
Retinitis pigmentosa (RP) is an inherited retinal degeneration caused by one of several
mistakes in the genetic code. Such mistakes are called mutations. The mutations cause
degeneration of rod photoreceptors which are responsible for vision in dim illumination
resulting in night blindness. After rod photoreceptors are eliminated, gradual degeneration
of cone photoreceptors occurs resulting in gradual constriction of side vision that
eventually causes tunnel vision. Oxidative stress contributes to cone degeneration.
N-acetylcysteine (NAC) reduces oxidative stress and in animal models of RP it slowed cone
degeneration. In a phase I clinical trial in patients with RP, NAC taken by month for 6
months caused some small improvements in two different vision tests suggesting that long-term
administration of NAC might slow cone degeneration in RP. NAC Attack is a clinical trial
being conducted at many institutions in the US, Canada, Mexico, and Europe designed to
determine if taking NAC for several years provides benefit in patients with RP.
Kimberly Stepien, MD
All
18 Years to 65 Years old
Phase 3
This study is NOT accepting healthy volunteers
NCT05537220
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Inclusion Criteria:
General
• Ability and willingness to provide informed consent
• Age ≥ 18 and ≤65 years at time of signing Informed Consent Form
• Ability and willingness to comply with the study protocol and to participate in all
study visits and assessments in the investigator's judgement
• For candidates of childbearing potential: willingness to use a method of contraception
• Agreement not to take supplements other than vitamin A
Ocular Inclusion Criteria
• Both eyes must exhibit the RP phenotype with evidence of loss of night vision, gradual
constriction of visual fields, and maintenance of visual acuity;
• In addition, an eye must meet the following criteria to be included in the study:
• Gradable EZ on a horizontal SD-OCT scan through the fovea center with width ≤ 8000 µm
and ≥1500 µm and with well-defined truncation at both the nasal and temporal sides;
• BCVA ≥ ETDRS letter score of 61 (20/60 Snellen equivalent);
• Sufficiently clear ocular media and adequate pupillary dilation to allow good quality
images sufficient for analysis and grading by central reading center.
Exclusion Criteria:
General Exclusion Criteria
• Active cancer within the past 12 months, except for appropriately treated carcinoma in
situ of the cervix, non-melanoma skin carcinoma, or prostate cancer with Gleason score
≤ 6 and stable prostate specific antigen for > 12 months
• Renal failure requiring renal transplant, hemodialysis, peritoneal dialysis, or
anticipated to require hemodialysis or peritoneal dialysis during the study
• Liver disease, cystic fibrosis, asthma, or chronic obstructive pulmonary disease
(COPD), history of thrombocytopenia not due to a reversible cause or other blood
dyscrasia
• Uncontrolled blood pressure (defined as systolic > 180 and/or diastolic > 100 mmHg
while at rest) at screening. If a patient's initial measurement exceeds these values,
a second reading may be taken 30 or more minutes later. If the patient's blood
pressure must be controlled by antihypertensive medication, the patient may become
eligible if medication is taken continuously for at least 30 days.
• History of other disease, physical examination finding, or clinical laboratory finding
giving reasonable suspicion that oral NAC may be contraindicated or that follow up may
be jeopardized
• Cerebrovascular accident or myocardial infarction within 6 months of screening
• Participation in an investigational study that involves treatment with any drug or
device within 6 months of screening
• Three relatives already enrolled in study
• Pregnant, breast feeding, or intending to become pregnant during the study treatment
period. Women of childbearing potential who have not had tubal ligation must have a
urine pregnancy test at screening.
• Known history of allergy to NAC
• Having taken NAC in any form in the past 4 months
• Phenylketonuria
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency
• Abnormal laboratory value including the value of alanine aminotransferase (ALT),
aspartate aminotransferase (AST), or bilirubin being greater than 1.5 x the upper
limit of normal
• Any major abnormal findings on blood chemistry, hematology, and renal function lab
tests that in the opinion of the Site Investigator and/or the Study Chair makes the
candidate not suitable to participate in the trial
• HIV or hepatitis B infection
Ocular Exclusion Criteria
• Evidence of cone-rod dystrophy or pattern dystrophy including focal areas of atrophy
or pigmentary changes in the central macula
• Cystoid spaces involving the fovea substantially reducing vision
• Glaucoma or other optic nerve disease causing visual field loss or reduced visual
acuity
• Intra ocular pressure >27 mm Hg from two measurements. If a patient's initial
measurement exceeds 27 mm Hg, a second reading must be taken.
• Any retinal disease other than RP causing reduction in visual field or visual acuity
• Any prior macular laser photocoagulation
• Intraocular surgery within 3 months prior to screening
• High myopia with spherical equivalent refractive error > 8 diopters. If an eye has had
cataract surgery or refractive surgery, a pre-operative refractive error spherical
equivalent > 8 diopters is an exclusion
• Any concurrent ocular condition that might affect interpretation of results
• History of uveitis in either eye
First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Advanced Solid Tumor Patients and in Combination With Fulvestrant in Patients With Advanced Breast Cancer
This is an open-label, FIH study designed to evaluate the maximum tolerated dose, recommended
Phase 2 dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic
activity of RLY-2608, in advanced solid tumor patients with a
Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in
blood and/or tumor per local assessment. The study will evaluate RLY-2608 as a single agent
for patients with unresectable or metastatic solid tumors, RLY-2608 + fulvestrant and
RLY-2608 + fulvestrant + CDK4/6 inhibitor (palbociclib or ribociclib) combination arms for
patients with HR+ HER2- locally advanced or metastatic breast cancer. The RLY-2608 single
agent arm, RLY-2608 + fulvestrant combination arm, and triple combination arms will have 2
parts: a dose escalation (Part 1) and a dose expansion (Part 2).
Kari Wisinski, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05216432
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Key Inclusion Criteria
Patient has ECOG performance status of 0-1
One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per local
assessment
•Other potentially oncogenic PIK3CA mutations may be considered but must be approved by
the Sponsor prior to enrollment.
Part 1 •Ability to provide archived tumor tissue or be willing to undergo pretreatment
tumor biopsy to assess PIK3CA status retrospectively Part 2 •Submit tumor tissue prior to
study drug initiation for determination of PIK3CA mutation retrospectively.
Key Inclusion for RLY-2608 Single Agent Arm
• [For Part 1]: Evaluable disease per RECIST v1.1
• [For Part 2]: Measurable disease per RECIST v1.1
• Disease that is refractory to standard therapy, intolerant to standard therapy, or has
declined standard therapy.
• Part 1- histologically or cytologically confirmed diagnosis of unresectable or
metastatic solid tumor
• Part 2 •Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of the
following tumor types:
Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group 3:
cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian, head
and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic solid
tumors with PIK3CA double mutations
Key Inclusion for Combination Arms
• [For Part 1 and Part 2]: Evaluable disease per RECIST v1.1
• Male or female with histologically or cytologically confirmed diagnosis of HR+, HER2-
unresectable or metastatic breast cancer that is not amenable to curative therapy.
Females may be postmenopausal, premenopausal, or perimenopausal. Premenopausal or
perimenopausal females must have a histologically or cytologically confirmed diagnosis
of HR+ HER2- advanced or metastatic breast cancer that is not amenable to curative
therapy and must have been previously treated with GnRH agonist at least 4 weeks prior
to start of study drug
• [For Part 1 and Part 2]: Had previous treatment for advanced or metastatic breast
cancer with:
1. ≤1 line of chemotherapy,
2. ≥1 cyclin-dependent kinases (CDK) 4/6 inhibitor, and
3. ≥1 antiestrogen therapy including, but not limited to, selective
estrogen-receptor degraders (eg, fulvestrant), selective estrogen receptor
modulators (eg, tamoxifen), and aromatase inhibitors (AI) (letrozole,
anastrozole, exemestane), and
4. ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation Note:
Systemic local, loco-regional, or adjuvant treatment is not to be included in
enumeration or previous treatment
[For RLY-2608 + fulvestrant arm; Part 2, Group 2]: Received prior treatment with a PI3Kα
inhibitor and discontinued the inhibitor due to intolerance and not disease progression,
where intolerance is defined as treatment discontinuation due to treatment related AE (eg.
hyperglycemia, rash, diarrhea, stomatitis) other than severe hypersensitivity reaction
and/or life-threatening reactions, such as anaphylaxis and Stevens-Johnson syndrome.
Key Exclusion Criteria
Prior treatment with PI3Kα, AKT, or mTOR inhibitors (except for RLY-2608 + fulvestrant arm,
Part 2, Group 2).
Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma glucose
≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%.
History of hypersensitivity to PI3K inhibitors. For combination arms only: hypersensitivity
to fulvestrant, palbociclib, and/or ribociclib, as appropriate for the combination.
For triple combination arms only: history of pneumonitis or interstitial lung disease.
For the single agent and combination arms other than with ribociclib: mean QT interval
corrected using Fridericia's formula (QTcF) >480 msec. For the combination arms with
ribociclib: mean QTcF ≥450 msec.
Patient has a history of prolonged QT syndrome or torsades de pointes. Patient has a
familial history of prolonged QT syndrome.
Clinically significant, uncontrolled cardiovascular disease CNS metastases or primary CNS
tumor that is associated with progressive neurologic symptoms
PIK3CA Mutation, Solid Tumor, Adult, HER2-negative Breast Cancer, Breast Cancer, Metastatic Breast Cancer, Advanced Breast Cancer, Unresectable Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
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