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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/26/2021.

Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitor BMS-986158 in Pediatric Cancer

Clinicaltrials.gov identifier NCT03936465

Recruitment Status Recruiting

First Posted May 3, 2019

Last update posted June 17, 2020

Study Description

Brief summary:

This research study is studying an investigational drug called BMS-986158 as a possible treatment for pediatric solid tumors, lymphoma, or brain tumors.

  • Condition or Disease:Solid Tumor, Childhood
    Lymphoma
    Brain Tumor, Pediatric
  • Intervention/Treatment: Drug: BMS-986158
  • Phase: Phase 1
Detailed Description

This is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied. The FDA (the U.S. Food and Drug Administration) has not approved BMS-986158 as a treatment for any disease. BMS-986158 is currently still being studied in adults. This is the first time that BMS-986158 will be evaluated in younger children, though children 12-17 years of age may also be included in parts of adult studies of BMS-986158. Research in the laboratory has shown that BMS-986158 may have activity against cancer cells. BMS-986158 belongs to a group of drugs called Bromodomain (BRD) and Extra-Terminal Domain (BET) inhibitors. These drugs block proteins that are important in reading DNA, which is a process important for cancer cells.

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 34 participants
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: Phase 1 Study of the Bromodomain (BRD) and Extra-Terminal Domain (BET) Inhibitor BMS-986158 in Pediatric Cancer
  • Actual Study Start Date: September 2019
  • Estimated Primary Completion Date: July 2022
  • Estimated Study Completion Date: July 2024
Arms and interventions
Arm Intervention/treatment
Experimental: Cohort A
Patients will receive BMS-986158 monotherapy orally for 5 days on / 2 days off per week in 28-day cycles. Patients with unselected relapsed or refractory solid tumors or lymphoma
Drug: BMS-986158
BMS-986158 belongs to a group of drugs called Bromodomain (BRD) and Extra-Terminal Domain (BET) inhibitors. These drugs block proteins that are important in reading DNA, which is a process important for cancer cells.
Experimental: Cohort B
Patients will receive BMS-986158 monotherapy orally for 5 days on / 2 days off per week in 28-day cycles. Patients with relapsed or refractory solid tumors, lymphoma, or CNS tumors that have defined molecular features predicted to increase sensitivity to BET inhibition
Drug: BMS-986158
BMS-986158 belongs to a group of drugs called Bromodomain (BRD) and Extra-Terminal Domain (BET) inhibitors. These drugs block proteins that are important in reading DNA, which is a process important for cancer cells.
Outcome Measures
  • Primary Outcome Measures: 1. Dose Limiting Toxicity Rate [ Time Frame: 28 days (first cycle) ]
    Dose limiting toxicity as defined in protocol
  • 2. The Rate of Toxicities of BMS-986158 [ Time Frame: 2 years ]
    Adverse events coded using CTCAE version 5
  • Secondary Outcome Measures: 1. Objective Response Rate [ Time Frame: 2 years ]
    Objective response rate
  • 2. Pharmacokinetics of BMS-986158 [ Time Frame: 2 years ]
    Plasma concentrations of BMS-986158
  • 3. Pharmacodynamics of BMS-986158 [ Time Frame: 2 years ]
    Gene expression levels in peripheral blood
  • 4. Blood Markers of Response [ Time Frame: 2 years ]
    Levels of ctDNA in peripheral blood
  • 5. CSF Markers of Response [ Time Frame: 2 years ]
    Levels of ctDNA in CSF
  • 6. Tumor Markers of Response [ Time Frame: 2 years ]
    Levels of Myc proteins in tumor
Eligibility Criteria
  • Ages Eligible for Study: 1 to 21 Year (Child, Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

- Age ≤ 21 years at time of enrollment. Note the requirement in section 3.1.6 that all
patients must be able to swallow intact capsules.

- Karnofsky performance status ≥ 50% for patients ≥16 years of age or Lansky ≥ 50% for
patients 50%
radiation of pelvis;

- At least 42 days must have elapsed if other substantial BM radiation;

- At least 42 days must have passed since last MIBG or other radionuclide therapy.

- Small molecule biologic therapy: At least 7 days following the last dose of a small
molecule biologic agent. For agents with known adverse events occurring beyond 7 days,
this duration must be extended beyond the time in which adverse events are known to
occur. If extended duration is required, this must be discussed with and approved by
the overall PI.

- Monoclonal antibody: At least 28 days must have elapsed after the last dose of
therapeutic monoclonal antibody.

- Myeloid growth factors: At least 14 days following the last dose of long-acting growth
factor (e.g. Neulasta) or 7 days following short-acting growth factor.

- Autologous hematopoietic stem cell transplant and stem cell boost: Patients must be at
least 60 days from day 0 of an autologous stem cell transplant or autologous stem cell
boost.

- Cellular therapies (including CAR-T cells) and other non-cellular, non-antibody
immunotherapies (e.g., vaccines): At least 42 days must have elapsed after last dose.

- Major Surgery: At least 2 weeks from prior major surgical procedure. Note: Major
surgical procedure will be considered all surgical procedures aside from the
following: Biopsy; central line placement/removal; bone marrow aspirate/biopsy; lumbar
puncture; dental procedures; gastrostomy tube placement; and VP shunt
placement/revision.

- BET inhibitors: Patients must not have received prior treatment with a BET inhibitor.

- Participants must have normal organ function as defined below.

- Bone Marrow Function

- For Patients without Documented Bone Marrow Involvement by Disease:

- Hemoglobin > 8 g/dL (may be transfused)

- Absolute neutrophil count ≥ 1,000 /uL

- Platelets ≥ 100,000 /uL and transfusion independent, defined as not receiving a
platelet transfusion for at least 5 days prior to CBC documenting eligibility.

- For Patients with Documented Bone Marrow Involvement by Disease:

- Hemoglobin > 8 g/dL (may be transfused)

- Absolute neutrophil count ≥ 750 /uL

- Platelets ≥ 75,000 /uL and transfusion independent, defined as not receiving a
platelet transfusion for at least 5 days prior to CBC documenting eligibility.

- Hepatic Function:

- Total bilirubin ≤ 1.5 x upper limit of normal for age (patients with known
Gilbert's may be considered after discussion with overall PI and if direct
bilirubin is at or below the upper limit of normal for age)

- ALT (SGPT) ≤ 3 x upper limit of normal (135 U/L) For the purpose of this study,
the ULN for ALT is 45 U/L

- Serum albumin > 2 g/dL

- Adequate Pancreatic Function:

--Lipase < upper limit of normal - Adequate GI Function: --Diarrhea < grade 1 by CTCAE version 5 - Coagulation Factors: - International Normalized Ratio (INR) < 1.5 - Partial thromboplastin time (PTT) < 1.5 times upper limit of normal - For patients having labs drawn via heparinized catheters, it is important to request heparin-absorbed values. - Adequate Cardiac Function: --QTc < 480 msec - Renal Function: - A serum creatinine within protocol limits based on age/sex. OR - Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels greater than the above age/sex maximum allowed values. - Able to swallow intact capsules. - Patient (or parent or legally authorized representative, if minor) is able to understand and willing to provide informed consent, using an institutionally approved informed consent procedure. - Participants of childbearing or child-fathering potential must agree to use adequate contraception throughout their participation following the guidance in Appendix H. Exclusion Criteria: - Prior solid organ or allogeneic stem cell transplantation. - Patients with primary or metastatic CNS tumors, except: - Patients with primary CNS tumor meeting definition for Cohort B; - Patients with a history of CNS metastatic disease that has been resected and/or radiated without evidence of active CNS disease for 3 months preceding enrollment; - Patients with lymphoma and CSF involvement. - Patients receiving any of the following prohibited foods and medications: - Agents listed in Appendix B within 7 days prior to enrollment - Grapefruit or Seville oranges and/or their juices within 7 days prior to enrollment - Non-steroidal anti-inflammatory drugs, oral anticoagulants, and therapeutic heparins (unfractionated or low molecular weight heparin) at the time of enrollment. Note: Use of heparin to maintain patency of a central or peripheral catheter is allowed - Other investigational agents being administered under an IND. - Pregnant participants will not be entered on this study given that the effects of BMS-986158 on the developing human fetus are unknown. Female participants of childbearing potential must have a documented negative pregnancy exam within 24 hours prior to dosing. - Breastfeeding mothers are not eligible, because there is an unknown risk for adverse events in nursing infants secondary to treatment of the mother with BMS-986158. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to BMS-986158. - Uncontrolled intercurrent illness including, but not limited to, ongoing or uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. - Patients with a known history of HIV, hepatitis B, and/or hepatitis C (testing not required as part of screening). - Patients with gastrointestinal disease or disorder that could interfere with absorption of BMS-986158, such as bowel obstruction or inflammatory bowel disease. - Patients with a body surface area < 0.3 m2

Contacts and Locations
Contacts

Contact: Steven G DuBois, MD,MS 617-632-5460 steven_dubois@dfci.harvard.edu

Locations

United States, Massachusetts
Dana Farber Cancer Institute
Boston

United States, Michigan
C.S. Mott Children's Hospital
Ann Arbor

Sponsors and Collaborators

Dana-Farber Cancer Institute

Stand Up To Cancer

Investigators

Principal Investigator: Steven G. DuBois, MD, MS Dana-Farber Cancer Institute

More Information
  • Responsible Party: Dana-Farber Cancer Institute
  • ClinicalTrials.gov Identifier: NCT03936465 History of Changes
  • Other Study ID Numbers: 19-040
  • First Posted: May 3, 2019 Key Record Dates
  • Last Update Posted: June 17, 2020
  • Last Verified: June 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: Yes
  • Studies a U.S. FDA-regulated Device Product: No
  • Keywords provided by Dana-Farber Cancer Institute: MYCN
    BRD4
    BET inhibitor
    Bromodomain
    Solid Tumor
    Neuroblastoma
    Sarcoma
    Medulloblastoma
    MYC
    Lymphoma