Study of Nivolumab (BMS-936558) in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in First-Line or in Switch Maintenance in Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) (CheckMate 012)
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Purpose
There is no formal research hypothesis to be statistically tested in this protocol.
- The study is evaluating the safety and tolerability of Nivolumab (BMS-936558) when combined with three platinum-based doublet chemotherapy regimens (Cisplatin/Gemcitabine; Cisplatin/Pemetrexed; and Carboplatin/Paclitaxel) in subjects with NSCLC.
- The study is evaluating the safety and tolerability of Nivolumab as maintenance therapy in combination with Bevacizumab/Avastin that will be given after at least 4 cycles of platinum doublet chemotherapy.
- The study is evaluating the safety and tolerability of Nivolumab in combination with Erlotinib among epidermal growth factor receptor (EGFR) mutation positive non-squamous NSCLC subjects and as monotherapy in subjects with NSCLC.
- The study is evaluating the safety and tolerability of Nivolumab in combination with Ipilimumab in subjects with squamous and non-squamous NSCLC.
- The study is evaluating the safety and tolerability of Nivolumab as switch maintenance therapy in subjects with squamous and non-squamous NSCLC.
- The study is evaluating the safety and tolerability of Nivolumab as monotherapy among subjects with untreated, asymptomatic brain metastases and have no evidence of cerebral edema.
| Condition | Intervention | Phase |
|---|---|---|
|
Non-small Cell Lung Cancer |
Biological: Nivolumab Drug: Gemcitabine Drug: Cisplatin Drug: Pemetrexed Drug: Paclitaxel Drug: Carboplatin Drug: Bevacizumab Drug: Erlotinib Biological: Ipilimumab |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Multi-arm Phase I Safety Study of Nivolumab in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in First-Line or in Switch Maintenance in Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) |
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of drug related adverse events [ Time Frame: Up to 100 days after the last dose of study drug (approximately 36 weeks) ] [ Designated as safety issue: Yes ]
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of serious adverse events [ Time Frame: Up to 100 days after the last dose of study drug (approximately 36 weeks) ] [ Designated as safety issue: Yes ]
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: At screening (up to 28 days prior to first treatment) ] [ Designated as safety issue: Yes ]
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 1 Day 1 ] [ Designated as safety issue: Yes ]
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 1 Day 8 ] [ Designated as safety issue: Yes ]
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 1 Day 15 ] [ Designated as safety issue: Yes ]
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 2 Day 1 ] [ Designated as safety issue: Yes ]
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 3 Day 1 ] [ Designated as safety issue: Yes ]
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 4 Day 1 ] [ Designated as safety issue: Yes ]
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Day 1 of every cycle from Cycle 4 until progression (approximately 24 weeks) ] [ Designated as safety issue: Yes ]
- Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: End of treatment (approximately 24 weeks) for subjects discontinued due to other reasons ] [ Designated as safety issue: Yes ]
- ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of subjects treated in arms A, B, C and D [ Time Frame: At screening (up to 28 days prior to first treatment), C4D1 (Week 10), every 6 weeks until C8D1, and then every 3 months thereafter until progression or end of treatment (approximately 24 weeks) for subjects discontinued due to other reasons ] [ Designated as safety issue: No ]
C4D1=Cycle 4 Day 1
C8D1=Cycle 8 Day 1
Objective Response Rate (ORR) is defined as the proportion of all treated subjects whose best overall response is either a complete response (CR) or partial response (PR)
- PFSR based on RECIST 1.1 of subjects treated in arms A, B, C and D [ Time Frame: At screening (up to 28 days prior to first treatment), C4D1 (Week 10), every 6 weeks until C8D1, and then every 3 months thereafter until progression or end of treatment (approximately 24 weeks) for subjects discontinued due to other reasons ] [ Designated as safety issue: No ]Progression Free Survival Rate (PFSR) is defined as the probability a subject remaining progression-free and/or surviving to 24 weeks. The probability will be calculated by the product limit method (Kaplan-Meier method) which takes into account censored data
- ORR based on RECIST 1.1 of subjects treated in arms E, F, K, L and M [ Time Frame: At screening (up to 28 days prior to first treatment), C6D1 (Week 11), C9D1 (Week 17), C12D1 (Week 23) and then every 3 months thereafter until progression (approximately 24 weeks) ] [ Designated as safety issue: No ]ORR is defined as the proportion of all treated subjects whose best overall response is either a CR or PR
- PFSR based on RECIST 1.1 of subjects treated in arms E, F, K, L and M [ Time Frame: At screening (up to 28 days prior to first treatment), C6D1 (Week 11), C9D1 (Week 17), C12D1 (Week 23) and then every 3 months thereafter until progression (approximately 24 weeks) ] [ Designated as safety issue: No ]PFSR is defined as the probability a subject remaining progression-free and/or surviving to 24 weeks. The probability will be calculated by the product limit method (Kaplan-Meier method) which takes into account censored data
- ORR based on RECIST 1.1 of subjects treated in arms G, H, I and J [ Time Frame: C4D1 (Week 10), C7D1 (Week 17), C10D1 (Week 23) and then every 3 months thereafter until disease progression (approximately 24 weeks) ] [ Designated as safety issue: No ]ORR is defined as the proportion of all treated subjects whose best overall response is either a CR or PR
- PFSR based on RECIST 1.1 of subjects treated in arms G, H, I and J [ Time Frame: C4D1 (Week 10), C7D1 (Week 17), C10D1 (Week 23) and then every 3 months thereafter until disease progression (approximately 24 weeks) ] [ Designated as safety issue: No ]PFSR is defined as the probability a subject remaining progression-free and/or surviving to 24 weeks. The probability will be calculated by the product limit method (Kaplan-Meier method) which takes into account censored data
| Estimated Enrollment: | 220 |
| Study Start Date: | December 2011 |
| Estimated Study Completion Date: | September 2014 |
| Estimated Primary Completion Date: | September 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm A: Nivolumab + Gemcitabine + Cisplatin
Nivolumab 10 mg/kg solution intravenously every 3 weeks until progressive disease (PD) or discontinuation due to toxicity. Administered over 60 minutes prior to chemotherapy on Day 1 of each cycle. A cycle is 3 weeks. Gemcitabine 1250 mg/M² solution intravenously on Day 1 and Day 8 of every 3 weeks cycle for 4 cycles Cisplatin 75 mg/M² solution intravenously on Day 1 of each 3 weeks cycle for 4 cycles |
Biological: Nivolumab
Other Name: BMS-936558
Drug: Gemcitabine
Drug: Cisplatin
|
|
Experimental: Arm B: Nivolumab + Pemetrexed + Cisplatin
Nivolumab 5 mg/kg solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes prior to chemotherapy on Day 1 of each cycle. A cycle is 3 weeks. Pemetrexed 500 mg/M² solution intravenously on Day 1 of every 3 weeks cycle for 4 cycles Cisplatin 75 mg/M² solution intravenously on Day 1 of each 3 weeks cycle for 4 cycles |
Biological: Nivolumab
Other Name: BMS-936558
Drug: Cisplatin
Drug: Pemetrexed
|
|
Experimental: Arm C: Nivolumab + Paclitaxel + Carboplatin
Nivolumab 0.3 mg/kg solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes prior to chemotherapy on Day 1 of each cycle. A cycle is 3 weeks. Paclitaxel 200 mg/M² solution intravenously on Day 1 of every 3 weeks cycle for 4 cycles Carboplatin area under curve (AUC) 6 solution intravenously on Day 1 of every 3 weeks cycle for 4 cycles |
Biological: Nivolumab
Other Name: BMS-936558
Drug: Paclitaxel
Drug: Carboplatin
|
|
Experimental: Arm D: Nivolumab + Bevacizumab maintenance
Nivolumab 5 mg/kg solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes prior to chemotherapy on Day 1 of each cycle. A cycle is 3 weeks. Bevacizumab 15 mg/kg administered over 90 minute intravenous infusion on Cycle 1 Day 1 followed by a 60 minute intravenous infusion every 3 weeks on Cycle 2 onwards and until PD or discontinuation due to toxicity. |
Biological: Nivolumab
Other Name: BMS-936558
Drug: Bevacizumab
|
|
Experimental: Arm E: Nivolumab + Erlotinib
Nivolumab 3 mg/kg solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes prior to chemotherapy on Day 1 of each cycle. A cycle is 2 weeks. Erlotinib 150 mg tablet by mouth daily until PD or discontinuation due to toxicity. |
Biological: Nivolumab
Other Name: BMS-936558
Drug: Erlotinib
|
|
Experimental: Arm F: Nivolumab
Nivolumab 3 mg/kg solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes. A cycle is 2 weeks.
|
Biological: Nivolumab
Other Name: BMS-936558
|
|
Experimental: Arm G: Nivolumab + Ipilimumab
In Squamous histology subjects (NSCLC) Nivolumab 1 mg/kg solution administered over 60 minutes intravenously prior to Ipilimumab on Day 1 of each cycle. A cycle is 3 weeks for combination regimen. Combination regimen will be provided for 4 cycles. Ipilimumab 3 mg/kg solution administered over 90 minutes intravenously on Day 1 of each cycle, every 3 weeks for 4 cycles. Followed by Nivolumab (3 mg/kg) administered every 2 weeks until PD or discontinuation due to toxicity. |
Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
|
|
Experimental: Arm H: Nivolumab + Ipilimumab
In non-squamous histology subjects (NSCLC) Nivolumab 1 mg/kg solution administered over 60 minutes intravenously prior to Ipilimumab on Day 1 of each cycle. A cycle is 3 weeks for combination regimen. Combination regimen will be provided for 4 cycles. Ipilimumab 3 mg/kg solution administered over 90 minutes intravenously on Day 1 of each cycle, every 3 weeks for 4 cycles. Followed by Nivolumab (3 mg/kg) administered every 2 weeks until PD or discontinuation due to toxicity. |
Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
|
|
Experimental: Arm I: Nivolumab + Ipilimumab
In squamous histology subjects (NSCLC) Nivolumab 3 mg/kg solution administered over 60 minutes intravenously prior to Ipilimumab on Day 1 of each cycle. A cycle is 3 weeks for combination regimen. Combination regimen will be provided for 4 cycles. Ipilimumab 1 mg/kg solution administered over 90 minutes intravenously on Day 1 of each cycle, every 3 weeks for 4 cycles. Followed by Nivolumab (3 mg/kg) administered every 2 weeks until PD or discontinuation due to toxicity. |
Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
|
|
Experimental: Arm J: Nivolumab + Ipilimumab
In non-squamous histology subjects (NSCLC) Nivolumab 3 mg/kg solution administered over 60 minutes intravenously prior to Ipilimumab on Day 1 of each cycle. A cycle is 3 weeks for combination regimen. Combination regimen will be provided for 4 cycles. Ipilimumab 1 mg/kg solution administered over 90 minutes intravenously on Day 1 of each cycle, every 3 weeks for 4 cycles. Followed by Nivolumab (3 mg/kg) administered every 2 weeks until PD or discontinuation due to toxicity. |
Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
|
|
Experimental: Arm K: Nivolumab
In squamous histology subjects (NSCLC) Nivolumab 3 mg/kg solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes as switch maintenance therapy. A cycle is 2 weeks. |
Biological: Nivolumab
Other Name: BMS-936558
|
|
Experimental: Arm L: Nivolumab
In non-squamous histology subjects (NSCLC) Nivolumab 3 mg/kg solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes as switch maintenance therapy. A cycle is 2 weeks. |
Biological: Nivolumab
Other Name: BMS-936558
|
|
Experimental: Arm M: Nivolumab
NSCLC subjects with untreated, asymptomatic brain metastases and have no evidence of cerebral edema Nivolumab 3 mg/kg solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes as monotherapy. A cycle is 2 weeks |
Biological: Nivolumab
Other Name: BMS-936558
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email MyCancerStudyConnect@emergingmed.com. Please visit www.BMSStudyConnect.com for more information on clinical trial participation.
Inclusion Criteria:
- Newly diagnosed and confirmed Stage IIIB/IV NSCLC
- Previously treated NSCLC with asymptomatic brain metastases (eligible for Arm M) See additional details below
- Men and women aged ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Subject must be chemotherapy naive (except Arm D, K, L and M). Prior use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is acceptable. For Arms D, K, and L, subjects must be non-progressors within 42 days after completion of first-line treatment with ≥4 cycles of Platinum Doublet chemotherapy with or without Bevacizumab. See below for Arm M
- Either a formalin fixed tissue block or a minimum of 10 slides of tumor sample (archived or fresh) must be available for biomarker evaluation (a local pathologist must review for adequacy of sampling)
- Life expectancy of at least 3 months
- Prior radiotherapy must have been completed at least 2 weeks prior to study entry
For Arm M:
- No more than 4 brain metastases
- Each brain metastases ≤3 cm in size
- No evidence of cerebral edema
- Subjects must be free of neurologic symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroids for ≥10 days prior to initiation of study treatment
- At least 1 measurable target brain lesion >0.5 cm and no larger than 3 cm in diameter and/or 2 measurable brain target lesions >0.3 cm
- No prior radiation therapy, surgery, or other local therapy for target brain lesions
- Must have received at least one prior systemic anticancer therapy for NSCLC
Exclusion Criteria:
- Subjects with symptomatic brain metastases, spinal cord compression, or intractable back pain due to a compressive or destructive mass
- Subjects who require emergent use of systemic steroids, emergent surgery and/or radiotherapy
- Any active or history of a known autoimmune disease
- Subjects with previous malignancies (except non-melanoma skin cancers, in situ bladder cancer, gastric, or colon cancers or cervical cancers/dysplasia, or breast carcinoma in situ) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period
- History of Grade ≥2 neuropathy
- Subjects with interstitial pneumonia or pulmonary fibrosis by imaging diagnosis of the chest or clinical symptoms
Contacts and Locations| Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email: | Clinical.Trials@bms.com | |
| Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time. |
| United States, California | |
| Ucla | Recruiting |
| Santa Monica, California, United States, 90404 | |
| Contact: Jonathan Goldman, Site 005 310-570-1453 | |
| United States, Connecticut | |
| Yale Cancer Center | Recruiting |
| New Haven, Connecticut, United States, 06520 | |
| Contact: Scott Gettinger, Site 014 203-785-4590 | |
| United States, Florida | |
| H. Lee Moffitt Cancer Center & Research Institute | Recruiting |
| Tampa, Florida, United States, 33612 | |
| Contact: Scott Antonia, Site 013 813-745-4960 | |
| United States, Maryland | |
| The Johns Hopkins University | Recruiting |
| Baltimore, Maryland, United States, 21287 | |
| Contact: Julie Brahmer, Site 001 | |
| United States, New York | |
| Memorial Sloan Kettering Cancer Center | Recruiting |
| New York, New York, United States, 10065 | |
| Contact: Naiyer Rizvi, Site 010 646-422-4631 | |
| United States, North Carolina | |
| Duke University Medical Center | Recruiting |
| Butner, North Carolina, United States, 27710 | |
| Contact: Neal Ready, Site 004 919-575-7213 | |
| United States, Pennsylvania | |
| Fox Chase Cancer Center | Recruiting |
| Philadelphia, Pennsylvania, United States, 19111 | |
| Contact: Hossein Borghaei, Site 016 215-214-4604 | |
| United States, Texas | |
| University Of Texas Southwestern Medical Center At Dallas | Recruiting |
| Dallas, Texas, United States, 75390 | |
| Contact: David E Gerber, Site 006 214-648-4155 | |
| United States, Washington | |
| Seattle Cancer Care Alliance | Recruiting |
| Seattle, Washington, United States, 98109 | |
| Contact: Laura Chow, Site 007 855-557-0555 | |
| Canada, Ontario | |
| Local Institution | Recruiting |
| Hamilton, Ontario, Canada, L8V 5C2 | |
| Contact: Site 008 | |
| Local Institution | Recruiting |
| Toronto, Ontario, Canada, M5G 2M9 | |
| Contact: Site 003 | |
| Canada, Quebec | |
| Local Institution | Recruiting |
| Ottawa, Quebec, Canada, K1H 8L6 | |
| Contact: Site 002 | |
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT01454102 History of Changes |
| Other Study ID Numbers: | CA209-012 |
| Study First Received: | September 16, 2011 |
| Last Updated: | May 15, 2013 |
| Health Authority: | Canada: Health Canada Canada: Ethics Review Committee United States: Food and Drug Administration United States: Institutional Review Board |
Additional relevant MeSH terms:
|
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Gemcitabine Pemetrexed Bevacizumab Cisplatin Carboplatin |
Paclitaxel Erlotinib Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors |
ClinicalTrials.gov processed this record on June 18, 2013