A Randomized, Open-label Phase 2 Clinical Trial of BMS-986012 in Combination with Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer
- Conditions
- cancerlung carcinoma10038666
- Registration Number
- NL-OMON54331
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 16
1. Participants must have histologically or cytologically documented Extensive
Stage Small Cell Lung Cancer (ES SCLC). Participants must present with
extensive stage IV disease based on the American Joint Committee on Cancer, 7th
edition guidelines. The following grades will be considered: T any, N any, M1a,
or M1b, or T3-4 due to multiple lung nodules that are too extensive or tumour
or nodal volume that is too large to be encompassed in a tolerable radiation
plan. 2. a. Archived tumor specimens, in the form of blocks or sectioned
slides, are mandatory for all participants except those participating in the
separate PET tracer sub-study for whom the archived tumor specimen is optional.
b. Participants taking part in the separate PET tracer sub-study must provide a
fresh tumor biopsy from any disease site (primary or metastatic). Mandatory
minimum of 3 cores to be processed as 2 fresh frozen and the rest as formalin
fixed paraffin embedded. Refer to Section 9.8.1 and the Laboratory Manual for
further details on procedures for collecting fresh tumor samples. Note: if
during the attempt to collect the tumor biopsy there are safety issues and a
sample may not be obtained or is not suitable for the study per protocol
requirements, the participant may still be allowed to enter in the study after
consultation with BMS Medical Monitor. 3. Eastern Cooperative Oncology Group
(ECOG) Performance Score (PS) 0 or 1. 4. Participants must have at least 1
measurable lesion, measured by computed tomography (CT) or magnetic resonance
imaging (MRI). This will be evaluated per Response Evaluation Criteria in Solid
Tumours version 1.1 (RECIST v1.1) criteria. 5. Participants must be suitable to
receive a platinum-based chemotherapy regimen as per locally approved drug
labels and institutional guidelines. 6. Adequate hematologic and end organ
function as defined below: a. Absolute neutrophil count >= 1,500/mm3 (stable off
any growth factor within 2 weeks of the first study drug administration) b.
Platelets >= 100,000/mm3 (transfusion to achieve this level is not permitted
within 2 weeks of the first study drug administration) c. Hemoglobin >= 9 g/dL
(transfusion to achieve this level is not permitted within 2 weeks of the first
study drug administration) d. White blood cells >= 2000/mm3 e. Total bilirubin <=
1.5 x upper limit of normal (ULN) f. Aspartate aminotransferase (AST; serum
glutamic-oxaloacetic transaminase) and alanine aminotransferase (ALT; serum
glutamic-pyruvic transaminase) <= 3 x ULN g. Serum creatinine <= 1.5 x ULN or
calculated creatinine clearance > 50 mL/min (using the Cockcroft-Gault formula)
7. Males and Females aged 18 years or older a. Women who are not of
childbearing potential are exempt from contraceptive requirements b. Women
participants must have documented proof that they are not of childbearing
potential c. Women of Childbearing Potential (WOCBP) must have a negative
highly sensitive urine or serum pregnancy test (minimum sensitivity 25 IU/L or
equivalent units of human chorionic gonadotropin (HCG) within 24 hours prior to
the start of study treatment). An extension up to 72 hours prior to the start
of study treatment is permissible in situations where results cannot be
obtained within the standard 24-hour window. d. WOCBP must agree to follow
instructions f
1. Medical Conditions a. Women who are pregnant or breastfeeding. b. Any
significant acute or chronic medical illness that would interfere with study
treatment or follow-up c. Inability to undergo venepuncture and/or tolerate
venous access. d. Any other sound medical, psychiatric, and/or social reason as
determined by the investigator e. Participants with symptomatic brain or other
central nervous system (CNS) metastases. Participants are eligible if brain or
other CNS metastases are asymptomatic and do not require immediate treatment or
have been adequately treated. They must have neurologically returned to
baseline (except for residual signs or symptoms related to the CNS treatment)
for at least 2 weeks prior to randomization. In addition, participants must be
either off corticosteroids or on a stable or decreasing dose of <= 10 mg daily
prednisone (or equivalent) for at least 2 weeks prior to randomization. f.
Paraneoplastic autoimmune syndrome requiring systemic treatment. g. History of
idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic
pneumonitis, organizing pneumonia, or evidence of active pneumonitis on
screening chest CT scan. History of radiation pneumonitis is permitted. h.
Grade >= 2 peripheral sensory neuropathy at study entry. i. Participant has
uncontrolled or active systemic fungal, bacterial, viral, or other infection
despite appropriate anti-infective treatment, within 7 days prior to the first
dose of study drug. j. Known human immunodeficiency virus (HIV) positive with
an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection
within the past year or a current CD4 count < 350 cells/uL. Participants with
known HIV are eligible if: i.) They have received antiretroviral therapy (ART)
for at least 4 weeks prior to randomisation as clinically indicated while
enrolled on study ii.) They continue on ART as clinically indicated while
enrolled on study iii.) CD4 counts and viral load are monitored as per standard
of care by a local health care provider. NOTE: Testing for HIV must be
performed at sites where mandated locally. HIV-positive participants must be
excluded where mandated locally (see Appendix 8). k. Significant uncontrolled
cardiovascular disease, including, but not limited to, any of the following:
i.) Uncontrolled hypertension, which is defined as systolic blood pressure >
160 mm Hg or diastolic blood pressure > 100 mm Hg, despite optimal medical
management. ii.) Active coronary artery disease, including unstable or newly
diagnosed angina within 3 months of study enrollment. iii.) Myocardial
infarction in the past 6 months. iv.) History of congenital long QT syndrome.
v.) History of clinically significant arrhythmias, such as ventricular
tachycardia, ventricular fibrillation, or Torsade de pointes. vi.)Uncontrolled
heart failure, defined as Class 3 or 4 by New York Heart Association functional
classification. vii.) History or current diagnosis of myocarditis. l.
Participants with an active, known or suspected autoimmune disease or
inflammatory disorder. Participants with type I diabetes mellitus,
hypothyroidism only requiring hormone replacement, skin disorders (such as
vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trig
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1. To assess the safety and tolerability for participants randomized to<br /><br>BMS-986012 in combination with carboplatin, etoposide, and nivolumab for 4<br /><br>cycles (induction) followed by BMS-986012 and nivolumab maintenance (Arm A) vs<br /><br>those randomized to carboplatin, etoposide, and nivolumab for 4 cycles<br /><br>(induction) followed by nivolumab maintenance (Arm B).<br /><br><br /><br>2. To compare the Progression Free Survival (PFS) as assessed by Blinded<br /><br>Independent Central Review (BICR) of participants treated in the combination<br /><br>induction and maintenance therapies of Arms A and B described above. Assessment<br /><br>will be based on RECIST v1.1 criteria</p><br>
- Secondary Outcome Measures
Name Time Method