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Trial record 1 of 3 for:    CheckMate-012
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Study of Nivolumab (BMS-936558) in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) (CheckMate 012)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01454102
Recruitment Status : Active, not recruiting
First Posted : October 18, 2011
Results First Posted : August 5, 2019
Last Update Posted : March 5, 2020
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE September 16, 2011
First Posted Date  ICMJE October 18, 2011
Results First Submitted Date  ICMJE December 19, 2017
Results First Posted Date  ICMJE August 5, 2019
Last Update Posted Date March 5, 2020
Actual Study Start Date  ICMJE December 9, 2011
Actual Primary Completion Date July 20, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 2, 2019)
  • Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death [ Time Frame: From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months) ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.
  • Number of Participants Who Experienced Selected Adverse Events [ Time Frame: From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months) ]
    The number of participants who experienced an AE of interest due to any cause is presented. Endocrine, Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, and Hypersensitivity/Infusion select AEs were identified that are potentially associated with the use of nivolumab, based on the following 4 guiding principles:
    • AEs that may differ in type, frequency, or severity from AEs caused by non-immunotherapies
    • AEs that may require immunosuppression (eg, corticosteroids) as part of their management
    • AEs whose early recognition and management may mitigate severe toxicity
    • AEs for which multiple event terms may be used to describe a single type of AE, thereby necessitating the pooling of terms for full characterization.
  • Number of Participants With Abnormalities in Selected Hepatic Clinical Laboratory Tests [ Time Frame: From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months) ]
    The number of subjects with selected hepatic laboratory abnormalities is reported. AST= aspartate aminotransferase; ALT= alanine aminotransferase; ULN= upper limit of normal.
  • Number of Participants With Abnormalities in Selected Thyroid Clinical Laboratory Tests [ Time Frame: From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months) ]
    The number of subjects with selected thyroid laboratory abnormalities is reported. FT3 and FT4 test abnormalities were considered for a 2-week window after the abnormal TSH test date. TSH= thyroid-stimulating hormone; FT3= Free T3; FT4= Free T4; LLN= lower limit of normal; ULN= upper limit of normal
Original Primary Outcome Measures  ICMJE
 (submitted: October 17, 2011)
  • Safety and tolerability of BMS-936558 in combination with chemotherapy measured by frequency of adverse events [ Time Frame: Up to 30 days after last dose of study drug (or longer) ]
  • Safety and tolerability of BMS-936558 in combination with chemotherapy measured by serious adverse events [ Time Frame: Up to 90 days after last dose of study drug (or longer) ]
  • Safety and tolerability of BMS-936558 in combination with chemotherapy measured by laboratory abnormalities and death [ Time Frame: Up to 90 days after last dose of study drug (expect to be 24 month) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 2, 2019)
  • Objective Response Rate (ORR) [ Time Frame: From first dose until date of progression or subsequent anti-cancer therapy (assessed up to July 2016, approximately 55 months) ]
    ORR was defined as the percentage of all treated participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria as per investigator assessment. This proportion was multiplied by 100 and expressed as a percentage. BOR was defined as the best response designation recorded between the date of randomization and the date of progression, or the date of subsequent anticancer therapy, whichever occurred first. CR or PR determinations included in the BOR assessment were confirmed by a second scan at least 4 weeks after the criteria for responses were first met. For participants without progression or subsequent therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial progression.
  • Progression-Free Survival Rate (PFSR) at Week 24 [ Time Frame: 24 weeks ]
    Progression-Free Survival (PFS) was defined as the time from the date of first dose of study medication to the date of first disease progression or death, if death occurred within 100 days of the final dose of study drug. Among participants without previous RECIST-defined progression, participants who died beyond 100 days and those who remained alive were censored at the last tumor assessment date (before subsequent therapy). PFSR at week 24 was defined as the proportion of subjects remaining progression free and surviving at 24 weeks. The proportion was calculated by the product-limit method (Kaplan-Meier estimate), which takes into account censored data, and expressed as a percentage.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2011)
  • Objective response rate (ORR) defined as the proportion of all treated subjects whose best response is either a complete response (CR) or partial response (PR) [ Time Frame: From the date of first dose of study drug until the date of first documented progression, or date of death, whichever come first (expect to be 24 month) ]
  • Disease control rate (DCR) defined as the proportion of all treated subjects whose best response is either a CR or PR or stable disease (SD) lasting for 24 weeks or greater [ Time Frame: From the date of first dose of study drug until date of first documented progression, or date of death, whichever come first (expect to be 24 month) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Nivolumab (BMS-936558) in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) (CheckMate 012)
Official Title  ICMJE 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 Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC)
Brief Summary
  • 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 no evidence of cerebral edema.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Biological: Nivolumab
    Other Name: BMS-936558
  • Drug: Gemcitabine
  • Drug: Cisplatin
  • Drug: Pemetrexed
  • Drug: Paclitaxel
  • Drug: Carboplatin
  • Drug: Bevacizumab
  • Drug: Erlotinib
  • Biological: Ipilimumab
Study Arms  ICMJE
  • Experimental: Arm A: Nivolumab + Gemcitabine + Cisplatin

    Nivolumab solution intravenously every 3 weeks until progressive disease (PD) or discontinuation due to toxicity. Administered prior to chemotherapy on Day 1 of each cycle

    Gemcitabine solution intravenously on Day 1 and Day 8 of every cycle for 4 cycles

    Cisplatin solution intravenously on Day 1 of each cycle for 4 cycles

    Interventions:
    • Biological: Nivolumab
    • Drug: Gemcitabine
    • Drug: Cisplatin
  • Experimental: Arm B: Nivolumab + Pemetrexed + Cisplatin

    Nivolumab solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered prior to chemotherapy on Day 1 of each cycle

    Pemetrexed solution intravenously on Day 1 of every cycle for 4 cycles

    Cisplatin solution intravenously on Day 1 of each cycle for 4 cycles

    Interventions:
    • Biological: Nivolumab
    • Drug: Cisplatin
    • Drug: Pemetrexed
  • Experimental: Arm C: Nivolumab + Paclitaxel + Carboplatin

    Nivolumab solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered prior to chemotherapy on Day 1 of each cycle

    Paclitaxel solution intravenously on Day 1 of every cycle for 4 cycles

    Carboplatin area under curve (AUC) 6 solution intravenously on Day 1 of every cycle for 4 cycles

    Interventions:
    • Biological: Nivolumab
    • Drug: Paclitaxel
    • Drug: Carboplatin
  • Experimental: Arm D: Nivolumab + Bevacizumab maintenance

    Nivolumab solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered prior to chemotherapy on Day 1 of each cycle

    Bevacizumab administered prior to intravenous infusion on Cycle 1 Day 1 followed by intravenous infusion every 3 weeks on Cycle 2 onwards and until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Drug: Bevacizumab
  • Experimental: Arm E: Nivolumab + Erlotinib

    Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered prior to chemotherapy on Day 1 of each cycle

    Erlotinib tablet by mouth daily until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Drug: Erlotinib
  • Experimental: Arm F: Nivolumab
    Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes
    Intervention: Biological: Nivolumab
  • Experimental: Arm G: Nivolumab + Ipilimumab

    In Squamous histology subjects (NSCLC)

    Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles

    Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles

    Followed by Nivolumab administered until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm H: Nivolumab + Ipilimumab

    In non-squamous histology subjects (NSCLC)

    Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles

    Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles

    Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm I: Nivolumab + Ipilimumab

    In squamous histology subjects (NSCLC)

    Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles

    Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles

    Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm J: Nivolumab + Ipilimumab

    In non-squamous histology subjects (NSCLC)

    Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles

    Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles

    Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm K: Nivolumab

    In squamous histology subjects (NSCLC)

    Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered as switch maintenance therapy. A cycle is 2 weeks

    Intervention: Biological: Nivolumab
  • Experimental: Arm L: Nivolumab

    In non-squamous histology subjects (NSCLC)

    Nivolumab 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

    Intervention: Biological: Nivolumab
  • Experimental: Arm M: Nivolumab

    NSCLC subjects with untreated, asymptomatic brain metastases and have no evidence of cerebral edema

    Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered for up to an hour as monotherapy. A cycle is 2 weeks

    Intervention: Biological: Nivolumab
  • Experimental: Arm N: Nivolumab + Ipilimumab

    In subjects with any histology (NSCLC)

    Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles

    Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles

    Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm O: Nivolumab + Ipilimumab

    Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

    Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm P: Nivolumab + Ipilimumab

    Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

    Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm Q: Nivolumab + Ipilimumab

    Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

    Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm R: Nivolumab + Ipilimumab

    Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

    Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm S: Nivolumab + Ipilimumab

    Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

    Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 1, 2017)
472
Original Estimated Enrollment  ICMJE
 (submitted: October 17, 2011)
60
Estimated Study Completion Date  ICMJE June 14, 2020
Actual Primary Completion Date July 20, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

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 lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01454102
Other Study ID Numbers  ICMJE CA209-012
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP