A first-in-human study to explore the BMS-986158 study drug for patients with advanced cancer
- Conditions
- Solid tumors and hematologic malignanciesMedDRA version: 20.0Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864MedDRA version: 20.1Level: LLTClassification code 10066481Term: Hematological malignancySystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-000324-29-BE
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 354
1. Signed Written IC
2. Target Population
a) Subjects must have a confirmed histologic or cytologic diagnosis of
one of the following malignancies for participation in the study:
Ovarian cancer
Triple negative breast cancer
Part 1 only: Small cell lung cancer
Part 2 only: Non-Small cell lung cancer
Part 2 only: Renal cell carcinoma
Part 2 only: Uveal melanoma
Part 2 only: Uterine carcinosarcoma
Part 2 only: Neuroendocrine prostate cancer
Part 2 only: Castration-resistant prostate cancer
Part 2 only: NUT-midline carcinoma
Part 2 only: Ewing sarcoma
Part 2 only: Burkitt's lymphoma/leukemia
Part 2 only: Double-hit lymphoma
Part 2 only: adolescent subjects with malignancies harboring genetic abnormalities likely sensitive to BET inhibition who have progressive disease with no effective therapeutic options
b) Subjects with controlled, treated brain metastasis
c) All subjects must have at least one measurable lesion at baseline
d) For Part 1, all subjects must have archival tumor tissue identified and available for correlative biomarker studies. For Part 2, both a pretreatment and on-treatment fresh biopsy must be provided.
e) Subjects must have a life expectancy of at least 3 months.
f) Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
g) Subjects who have undergone any major surgery within 4 weeks of study drug administration are excluded.
h) Prophylactic anticoagulation for venous access devices with low-dose heparin or similar (e.g. heparin catheter flush) will be permitted.
i) For antiplatelet agents, prophylactic doses are permitted
j) Subject Re-enrollment: This study permits the re-enrollment of a subject that has discontinued the study as a pre-treatment failure
k) Subjects with solid tumor types that are not included in the preferred target population may also be enrolled after a minimum of 2 subjects with the preferred tumor types have been enrolled at a single dose level during escalation
l) Androgen Receptor Deprivation (ARD) therapy is permitted for subjects with prostate cancer at doses defined by the investigator if the therapeutic agent is not a strong inducer or inhibitor of CYP3A4 activity.
m) If biomarker result from the Foundation Medicine Inc test is inconclusive, Foundation Medicine Inc will repeat the test. If there is not enough tumor material, the tumor biopsy must be repeated.
3. Previous Treatment
a) Prior anticancer therapy treatments such as chemotherapy, radiotherapy, biological immunotherapy, or investigational agents are permitted.
i) For cytotoxic agents, at least 4 weeks must have elapsed from last dose of prior cytotoxic anticancer therapy and the initiation of study drug administration.
ii) For non-cytotoxic agents, at least 4 weeks or 5 half-lives (whichever is shorter) must have elapsed from the last dose of prior non-cytotoxic anticancer therapy and the initiation of study drug administration.
b) All acute toxicities, from any prior therapy (radiotherapy, chemotherapy, or surgical procedures) must have resolved to Grade = 1, NCI CTCAE, version 4.03 or to baseline if irreversible.
c) Concomitant therapy with bisphosphonates is acceptable as per American Society of Clinical Oncology (ASCO) guidelines. Doses of bisphosphonates must be stable for at least 30 days prior to treatment initiation, as per ASCO guidelines.
4. Age and Reproductive Status
a) Males and Females, 12 years of age or greater at the time of informed consen
1. Medical History and Concurrent Diseases
a) Evidence of uncontrolled, active infection, requiring parenteral antibacterial, anti-viral or anti-fungal therapy < 7 days prior to administration of study medication
b) Current or recent (within 3 months of study drug administration) gastrointestinal disease. Non-chronic conditions (eg, infectious diarrhea) that are completely resolved for at least 2 weeks prior to starting study treatment are not exclusionary
c) Subjects with concomitant second malignancies (except adequately treated nonmelanomatous skin cancers or in situ bladder, breast or cervical cancers) are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the study period
d) Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
e) History of medically significant thromboembolic events or bleeding diathesis within the past 6 months, such as cerebrovascular accident (including transient ischemic attacks), pulmonary embolism, pulmonary hemorrhage > 2 teaspoonfuls/24hrs or repeated pulmonary hemorrhage, gastrointestinal hemorrhage requiring transfusion or procedural intervention
f) Uncontrolled or significant cardiovascular disease including:
i) Congestive heart failure New York Heart Association [NYHA] Class 3 or greater within 3 months
ii) History of congenital long QT syndrome or clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsade de Pointes). Controlled atrial fibrillation is not an exclusion criterion
iii) Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction in the past 6 months
g) Inability to tolerate oral medication.
h) HIV-related disease or known positivity for human immunodeficiency virus (HIV).
i) History of and chronic hepatitis evidenced
j) Any other sound medical, psychiatric and/or social reason as determined by the investigator.
k) Use of strong inhibitors of CYP3A4 or P-gp within 1 week or 5 halflives
(whichever is longer) or strong inducers of CYP3A4 or P-gp within 2 weeks or 5 half-lives (whichever is longer).
l) Current uncontrolled autoimmune pneumonitis
m) Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 12 weeks prior to study treatment. The use of inactivated seasonal influenza vaccines, eg, Fluzone®, will be permitted on study without restriction.
n) Uncontrolled endocrine disorder including thyroid disease
o) Prior organ allograft or allogenic hematopoeitic stem cell transplantation (HSCT)
p) Participants with active, known or suspected autoimmune disease. Note the following exceptions: Participants with: vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Grave’s disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid-stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or c
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method