A first-in-human study to explore the BMS-986158 study drug for patients with advanced cancer
- Conditions
- Serious ovarian cancer with wild-type BRCA1/2, triple negative breast cancer and small cell lung cancerMedDRA version: 19.0Level: PTClassification code 10041067Term: Small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-000324-29-NL
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
1. Signed Written Informed Consent
2. Target Population
a) Subjects with a confirmed histologic/cytologic diagnosis of one of the following preferred malignancies for participation in the study and meet the other criteria listed (a specific exception for disease diagnosis criteria is noted in inclusion criteria k)
i) Ovarian cancer
(1) Histological or cytological documented epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer.
(2) Received at least one prior Platinum Based Therapy regimen.
(3) Have platinum-resistant/refractory disease, be intolerant of platinum-containing compounds, and/or have hypersensitivity to platinum-containing compounds.
(4) For Part 2A Expansion only: All subjects must have serous histology and have germline wild-type BRCA1 and BRCA2
ii) Triple negative breast cancer
(1) Women with histological or cytological confirmed triple negative breast carcinoma as defined by ASCO/CAP guidelines.
(2) Had progression or refractory disease during or after at least 1 chemotherapy regimen
iii) Small cell lung cancer
(1) Histologically or cytologically documented SCLC.
(2) Received at least one prior Platinum Based Therapy regimen.
b) Subjects with controlled, treated brain metastasis fulfilling all the following criteria may be screened: no radiographic progression for at least 2 weeks following radiation and/or surgical treatment, off steroids for at least 2 weeks, without new or progressing neurological signs or symptoms.
c) All subjects must have at least one measurable lesion at baseline by CT or MRI as per RECIST v1.1
d) All subjects must have archival tumor tissue identified and available for correlative biomarker studies unless a fresh biopsy is provided. All subjects not providing a fresh biopsy must consent to provide tumor blocks or slides to the sponsor and the availability of the tissue must be confirmed prior to subjects receiving study medication. If an archived tumor specimen is unavailable or unsuitable for correlative biomarker studies, subjects may consent to a pre-treatment fresh tumor biopsy to be eligible for this study if it can be performed at minimal acceptable clinical risk as judged by the Investigator and if it does not include a target lesion or lesion in an area treated with prior radiation therapy. For the first 25 ovarian subjects enrolled in dose expansion Part 2A, 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 are excluded. Subjects must have recovered from the effects of major surgery at least 14 days before first dose.
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 (e.g. aspirin < 300 mg daily, clopidogrel < 75 mg daily)
j) This study permits the re-enrollment of a subject that has discontinued the study as a pre treatment failure. If re-enrolled, the subject must re-consent.
3. Previous Treatment
a) Prior anti-cancer treatments [therapeutic or diagnostic] are permitted.
b) All acute toxicities, from any prior therapy must have resolved to Grade = 1, NCI CTCAE, version 4.03 or to baseline if irreversible.
c) Concomitant therapy with bio
1. Medical History and Concurrent Diseases
a) Evidence of uncontrolled, active infection, requiring parenteral anti-bacterial, 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 such as chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea. Non-chronic conditions (e.g. 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) Conditions requiring chronic systemic glucocorticoid use, such as autoimmune disease or severe asthma
e) History of medically significant thromboembolic events or bleeding diathesis within the past 6 months
f) Uncontrolled or significant cardiovascular disease including:
i) Congestive heart failure NYHA (New York Heart Association) 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) Past or active hepatitis B or C infection.
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 half-lives (whichever is longer) or strong inducers of CYP3A4 or P-gp within 2 weeks or 5 half-lives (whichever is longer).
2. Physical and Laboratory Test Findings
a) Inadequate bone marrow function defined as:
i) Absolute neutrophil count (ANC) < 1,500 cells/mm3;
ii) Platelet count < 100,000 cells/mm3;
iii) Hemoglobin < 8 g/dL
b) Abnormal blood coagulation parameters:
i) PT such that international normalized ratio (INR) is > 1.5x ULN (or > 2.5 x baseline, if a subject is on a stable dose of therapeutic warfarin) or a PTT > 1.2x upper limit of normal (ULN).
c) Inadequate hepatic function defined as:
i) Aspartate aminotransferase (AST) > 3x ULN
ii) Alanine aminotransferase (ALT) > 3x ULN
iii) Total bilirubin > 1.5 x ULN (except known Gilbert’s syndrome, direct bilirubin >
1.5x ULN);
d) Inadequate renal function defined as:
i) Creatinine clearance (CrCl) = 50 mL/minute (either measured or calculated using a standard formula such as Cockcroft and Gault) within 14 days prior to randomization
e) Any of the following on 12-lead electrocardiogram (ECG) prior to study drugadministration, confirmed by repeat.
i) QRS = 120 msec, except right bundle branch block
ii) QTcF > 450 msec
3. Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
c) Inability to comply with restrictions and prohibited activities/treatments as listed in protocol.
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