PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers

Phase I/II Trial of PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers

Background:

Drugs known as poly-adenosine diphosphate ribose polymerase (PARP) inhibitors are known to help stop tumor growth in patients with breast, ovarian cancers and many other cancers including prostate and pancreatic cancers. Many research studies done in animals and human cells have shown that these types of drugs can improve how well chemotherapy works. Standard chemotherapy can be too toxic to be combined with PARP inhibitors. In this study, we use a new form of chemotherapy called PLX038 (PEGylated SN38) to see if it can be safely combined with PARP inhibitors to shrink tumors.

Objective:

To find a safe combination of PLX038 and rucaparib, and to see if this mix will cause tumors to shrink.

Eligibility:

People age 18 and older with solid tumors, small cell lung cancer (SCLC), or small cell cancer outside their lungs.

Design:

Participants will be screened with:

Physical exam

Blood tests

Records of their diagnosis (or they will have a tumor biopsy).

A review of their symptoms and medications.

A review of their ability to perform their normal activities.

Electrocardiograms, to measure the electrical activity of the heart.

Computed tomography (CT) scans of the chest, abdomen, and pelvis. CT scans are a series of X-rays.

Participants will get PLX038 by intravenous catheter on Day 1 of each cycle (1 cycle = 21 days). For this, a small plastic tube is put into an arm vein. They will take rucaparib twice daily by mouth on Days 3 to 19 of each cycle. They will keep a medicine diary.

Participants may give a hair sample. They may have optional tumor biopsies.

Screening tests are repeated throughout the study.

About 30 days after treatment ends, participants will have a safety follow-up visit. They will give blood samples, talk about their health, and get a physical exam. Then they will be called or emailed every 6 months....

Study Overview

• Status: Active, not recruiting
• Conditions: Small Cell Lung Cancer; Extra-Pulmonary Small Cell Carcinomas
• Intervention / Treatment: Drug: PLX038; Drug: Rucaparib; Drug: Ondansetron

Detailed Description

Background:

• We hypothesize that a dose-escalation strategy that incorporates tumor targeted deoxyribonucleic acid (DNA)-damaging chemotherapy and DNA-damage response (DDR) inhibitors could allow safe and effective administration of DNA damage response (DDR) inhibitor-chemotherapy combination.
• PLX038 is a PEGylated conjugate of SN38 with improved properties including increased solubility, higher exposure and longer half-life. SN-38 is the active metabolite of CPT-11 (irinotecan) that inhibits topoisomerase 1 (Top1) and causes DNA strand breakage. As a specific DNA damaging agent, SN-38 enhances cell kill in tumors deficient in the DNA-damage response and when combined with inhibitors of the DDR.
• Rucaparib is a potent oral poly ADP ribose polymerase (PARP) inhibitor that is approved for the maintenance treatment of participants with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
• We hypothesize that the combination of PLX038 plus rucaparib is more efficacious than either agent alone.

Objectives:

• Phase I: To identify the maximum tolerated dose (MTD) of PLX038 in combination with rucaparib.
• Phase II: To assess the efficacy with respect to clinical benefit rate (CBR) (CR+PR+SD) for 4 months according to Response Evaluation Criteria (RECIST 1.1) of a combination of PLX038 and rucaparib in participants with small cell lung cancer and extra-pulmonary small cell carcinomas.

Eligibility:

• Subjects with histologically confirmed solid tumors (Phase I) OR histologically or cytologically confirmed small cell lung cancer (SCLC) (Phase II) OR histologically or cytologically confirmed extra-pulmonary small cell carcinomas (Phase II).
• Age greater than or equal to 18 years
• Subjects must have evaluable, or measurable disease.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
• Adequate organ function

Design:

• This is an open label Phase I/II trial accruing initially one cohort to determine maximum tolerated dose (MTD) of combined treatment of PLX038 and rucaparib (Phase I); and to examine the safety and efficacy of PLX038 in combination with rucaparib in the following cohort (Phase II).
• PLX038 will be administered by intravenous (IV) infusion on day 1 of every 21-days cycle, rucaparib will be administered by mouth (PO) twice daily on days 6 to 19 of every cycle.
• Treatment will continue until progression or unacceptable toxicity.
• Biomarkers of participant response to treatment will be investigated in an exploratory manner pre- and post-treatment.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

• Subjects with:

  • histologically confirmed solid tumors (Phase I), OR
  • histologically or cytologically confirmed small cell lung cancer (SCLC) (Phase II), OR
  • histologically or cytologically confirmed extra-pulmonary small cell carcinomas (Phase II).
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of PLX038 (PEGylated SN38) in combination with rucaparib in participants <18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Subjects must have progressed on or after standard first-line systemic chemotherapy and have no effective treatment options.
• Participants must have disease that is not amenable to potentially curative resection.
• Participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Participants with asymptomatic brain metastases and treated brain metastases are eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.

• Adequate hematological function defined by:

  • white blood cell (WBC) count greater than or equal to 3 x 10^9/L,
  • absolute neutrophil count (ANC) greater than or equal to 1.5 x10^9/L,
  • platelet count greater than or equal to 100 x 10^9/L,
  • Hemoglobin (Hgb) greater than or equal to 9 g/ dL

• Adequate hepatic function defined by:

  • a total bilirubin level less than or equal to 1.5 x upper limit of normal (ULN),
  • an aspartate aminotransferase (AST) level less than or equal to 2.5xULN, (less than or equal to 5X ULN if liver metastasis)
  • an alanine transaminase (ALT) level less than or equal to 2.5 xULN, (less than or equal to 5X ULN if liver metastasis).

• Adequate renal function defined by:

  • Creatinine OR Measured, or calculated creatinine clearance (CrCl) (estimated glomerular filtration rate (eGFR) may also be used in place of CrCl): < 1.5x institution upper limit of normal OR greater than or equal to 45 mL/min/1.73 m^2 for participant with creatinine levels greater than or equal to 1.5 X institutional ULN.

Note: Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard.

• The effects of the study treatment on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment and up to 6 months after the last dose of the study drug (s). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Subjects must be able to understand and willing to sign a written informed consent document.

EXCLUSION CRITERIA:

• Participants who are receiving any other investigational agents.
• Systemic anti-cancer treatment or major surgery within 2 weeks prior to enrollment.
• Radiotherapy within 24 hours prior to enrollment.
• Participants who require treatment with strong inhibitors or inducers of Cytochrome P450, family 3, subfamily A (CYP3A) or with uridine diphosphate glucuronosyltransferase 1A1 gene (UGT1A1) inhibitors during the planned period of investigational treatment with PLX038.
• Participants with known Gilbert's syndrome.
• Participants homozygous for the UGT1A1*28 variant allele with severely reduced UGT1A1 activity.
• Participants with known human immunodeficiency virus (HIV), hepatitis C virus (HCV), Hepatitis B virus (HBV) status on antiviral drugs are excluded due to the absence of previous experience with concurrent use of antiviral medications and the investigational drug product to be evaluated in the current study and possible for adverse pharmacokinetic and/or pharmacodynamic interactions.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to PLX038 or rucaparib.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that may impair the participants tolerance of study treatments.
• Pregnant women are excluded from this study because PEGSN38 and rucaparib potential for teratogenic or abortifacient effects are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with PEGSN38 and rucaparib, breastfeeding should be discontinued if the mother is treated with study drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I Arm 1 Level -1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 200 mg; Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 200 mg by mouth (PO)	Drug: PLX038; Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days).; Other Names: PEGylated SN38; Drug: Rucaparib; Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.; Other Names: Rubraca; Drug: Ondansetron; Participants will be recommended to have 8 mg of ondansetron taken with a small meal or snack to prevent nausea and vomiting approximately 30 minutes prior to each dose of rucaparib.; Other Names: Zofran
Experimental: Phase I Arm 1 Level 1, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 400 mg; Phase I - Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 400 mg by mouth (PO)	Drug: PLX038; Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days).; Other Names: PEGylated SN38; Drug: Rucaparib; Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.; Other Names: Rubraca; Drug: Ondansetron; Participants will be recommended to have 8 mg of ondansetron taken with a small meal or snack to prevent nausea and vomiting approximately 30 minutes prior to each dose of rucaparib.; Other Names: Zofran
Experimental: Phase I - Arm 1 Level 1A, PLX038 (PEGylated SN38) 1.3 g/m^2 and Rucaparib 300 mg; Phase I Participants with solid tumors enrolled to PLX038 (PEGylated SN38) and rucaparib escalation dose levels. PLX038, every 3 weeks, 1.3 g/m^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 300 mg by mouth (PO)	Drug: PLX038; Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days).; Other Names: PEGylated SN38; Drug: Rucaparib; Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.; Other Names: Rubraca; Drug: Ondansetron; Participants will be recommended to have 8 mg of ondansetron taken with a small meal or snack to prevent nausea and vomiting approximately 30 minutes prior to each dose of rucaparib.; Other Names: Zofran
Experimental: Phase IIA Arm 2; Phase IIA Participants with small cell lung cancer (SCLC) enrolled at the maximum tolerated dose (MTD) of PLX038 (PEGylated SN38) and rucaparib after the MTD of PLX038 and rucaparib is established. Level 2, PLX038, every 3 weeks, 1.3 g/m^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 3, PLX038, every 3 weeks, 1.7 g/m^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 4, PLX038, every 3 weeks, 2.3 g/m^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 2A PLX038, every 3 weeks, 1.3 g/m^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 400 mg by mouth (PO); and/or Level 3A. PLX038, every 3 weeks, 1.3 g/m^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 600 mg by mouth (PO).	Drug: PLX038; Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days).; Other Names: PEGylated SN38; Drug: Rucaparib; Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.; Other Names: Rubraca; Drug: Ondansetron; Participants will be recommended to have 8 mg of ondansetron taken with a small meal or snack to prevent nausea and vomiting approximately 30 minutes prior to each dose of rucaparib.; Other Names: Zofran
Experimental: Phase IIB Arm 2; Phase IIB Participants with extra-pulmonary small cell carcinomas enrolled at the maximum tolerated dose (MTD) of PLX038 (PEGylated SN38) and rucaparib after the MTD of PLX038 and rucaparib is established. Level 2, PLX038, every 3 weeks, 1.3 g/m^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 3, PLX038, every 3 weeks, 1.7 g/m^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 4, PLX038, every 3 weeks, 2.3 g/m^2, intravenous (IV); Rucaparib, days 3-19 twice a day (BID), total dose, 600 mg by mouth (PO); Level 2A PLX038, every 3 weeks, 1.3 g/m^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 400 mg by mouth (PO); and/or Level 3A. PLX038, every 3 weeks, 1.3 g/m^2, intravenous (IV); Rucaparib, days 5-19 twice a day (BID), total dose, 600 mg by mouth (PO).	Drug: PLX038; Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. PLX038 (PEGylated SN38) will be administered as a 1 hour (-10 minutes / +30 minutes) intravenous (IV) infusion on Day 1 of each cycle (21 days).; Other Names: PEGylated SN38; Drug: Rucaparib; Phase I: Dose escalation will follow the classical 3+3 trial design by Fibonacci sequence. Phase II: Maximum tolerated dose (MTD) identified in phase I. Rucaparib will be given orally at designated dose twice a day on days 5 to 19 of every 21-day cycle.; Other Names: Rubraca; Drug: Ondansetron; Participants will be recommended to have 8 mg of ondansetron taken with a small meal or snack to prevent nausea and vomiting approximately 30 minutes prior to each dose of rucaparib.; Other Names: Zofran

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II: Clinical Benefit Rate	Assess the efficacy with respect to clinical benefit rate (CBR) (Complete Response (CR)+ partial response (PR)+ stable disease (SD) for 4 months according to Response Evaluation Criteria (RECIST 1.1) of a combination of PLX038(PEGylated SN38) and rucaparib in previously treated participants with small cell lung cancer and extra-pulmonary small cell carcinomas. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.	Disease progression at 4 months
Phase I: Maximum Tolerated Dose (MTD) of PLX038 (PEGylated SN38) in Combination With Rucaparib	Maximum tolerated dose (MTD) of PLX038 (PEGylated SN38) in combination with rucaparib. The MTD is the dose level at which no more than 1 of 6 participants experience dose limiting toxicity (DLT) during the DLT evaluation period, and the dose below that at which at least 2 (of 6) participants have DLT as a result of the drug. A DLT is (if deemed drug-related) a Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia or grade 3 thrombocytopenia complicated with hemorrhage; Grade 4 anemia that does not resolve within 7 days despite optimal therapy; Inability to begin subsequent treatment course within 21 days of the scheduled date, due to study drug toxicity.	One cycle, approximately 21 (+7) days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I and Phase II Grades 1-5 Serious and/or Non-serious Adverse Events Related to PLX038 (PEGylated SN38) and/or Rucaparib	The safety of the treatment will be monitored, and any toxicities identified will be reported by type and grade. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.	Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.
Phase IIA Progression-free Survival (PFS)	Among participants in the phase IIA cohort, median progression free survival (PFS) will be calculated from the on-study date using the Kaplan-Meier method, along with 95% confidence intervals on the median PFS. PFS is defined as the time from on-study date to documented evidence of disease progression. Disease progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And appearance of one or more new lesions.	Time from the on-study date to documented evidence of disease progression
Phase IIA Overall Survival	Among participants in the phase IIA cohort, median overall survival (OS) will be calculated from the on-study date using the Kaplan-Meier method, along with 95% confidence intervals on the median OS.OS is defined as the date of on-study to the date of death from any cause or last follow-up.	Date of on-study to the date of death from any cause or last follow-up
Phase I - Number of Participants Who Experience a Clinical Response (Complete Response (CR)+Partial Response (PR)	The number of participants who experience a clinical response (Complete Response (CR)+Partial Response (PR) will be reported. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions; any pathological lymph nodes must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	Disease progression, a median of 43 days with range of 20 to 350 days.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I Number of Participants With a Dose Limiting Toxicity (DLT)	A DLT is (if deemed drug-related) Grade 4 neutropenia that does not resolve within 7 days; Grade 4 thrombocytopenia or grade 3 thrombocytopenia complicated with hemorrhage; Grade 4 anemia that does not resolve within 7 days despite optimal therapy; Inability to begin subsequent treatment course within 21 days of the scheduled date, due to study drug toxicity.	One cycle, approximately 21 days
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	Date first signed consent to date off study, approximately 21 months and 18 days; and 2 months and 5 days for each group respectively.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Anish Thomas, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2020
• Primary Completion (Actual): August 13, 2021
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 21, 2019
• First Submitted That Met QC Criteria: December 21, 2019
• First Posted (Actual): December 24, 2019

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: PARP Inhibitor; Chemotherapy; DDR Inhibitor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Small Cell; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Poly(ADP-ribose) Polymerase Inhibitors; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Rucaparib; Ondansetron
• Other Study ID Numbers: 200013; 20-C-0013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No