Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Head and Neck Carcinoma (CheckMate 141)

• Sponsor: Bristol-Myers Squibb
• Collaborator: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

Brief Summary:

The purpose of this study is to find out whether Nivolumab will significantly improve overall survival as compared to therapy of investigator's choice in patients with recurrent or metastatic head and neck carcinoma.

Condition or disease	Intervention/treatment	Phase
Squamous Cell Carcinoma of the Head and Neck	Drug: Nivolumab; Drug: Cetuximab; Drug: Methotrexate; Drug: Docetaxel	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	506 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open Label, Randomized Phase 3 Clinical Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Actual Study Start Date :	May 1, 2014
Actual Primary Completion Date :	November 6, 2015
Estimated Study Completion Date :	October 27, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A: Nivolumab; Nivolumab 3mg/kg intravenous (IV) Solution for Injection every 2 weeks until disease progression	Drug: Nivolumab; Other Name: BMS-936558
Active Comparator: Arm B: Cetuximab/Methotrexate/Docetaxel; Cetuximab intravenous (IV) Solution for Injection 400 mg/m2 (first dose) then 250 mg/m2 weekly until disease progression OR Methotrexate intravenous (IV) Solution for Injection 40 or 60 mg/m2 weekly until disease progression OR Docetaxel intravenous (IV) Solution for Injection 30 or 40 mg/m2 weekly until disease progression	Drug: Cetuximab; Drug: Methotrexate; Drug: Docetaxel

Outcome Measures

Primary Outcome Measures :

1. Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint [ Time Frame: From date of randomization to date of death, approximately 18 months ]
   Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Median OS time was calculated using Kaplan-Meier (KM) method. Hazard ratio (HR) and the corresponding Confidence Interval (CI) were estimated in a stratified Cox proportional hazards model for distribution of OS in each randomized arm. Interim analysis (Primary Endpoint) occurred at 218 deaths.
2. Overall Survival (OS) Rate in All Randomized Participants at Primary Endpoint [ Time Frame: Randomization to 3, 6, 9, and 12 months ]
   The overall survival rate is the probability that a participant will be alive at 3, 6, 9, and 12 months following randomization. Overall survival was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.

Secondary Outcome Measures :

1. Progression-Free Survival (PFS) [ Time Frame: Randomization to disease progression or death, whichever occurs first; Approximately 5 years ]
   PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator (as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria), or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants without any on study tumor assessments and did not die were censored on their date of randomization. Participants who received subsequent systemic anti-cancer therapy prior to documented progression were censored at the date of the last tumor assessment prior to the initiation of the new therapy.
2. Objective Response Rate (ORR) [ Time Frame: Randomization to disease progression or study drug is discontinued, whichever occurs first; Approximately 5 years ]
   ORR was defined as the proportion of randomized participants who achieved a best response of complete response (CR) or partial response (PR) using the RECIST1.1 criteria as per investigator assessment. Best overall response (BOR) was defined as the best response designation, recorded between the date of randomization and the date of progression, as assessed by the investigator per RECIST 1.1 or the date of subsequent anticancer therapy (including tumor-directed radiotherapy and tumor-directed surgery), whichever occurs first. For participants without evidence of RECIST 1.1 progression or subsequent anticancer therapy, all available response assessments will contribute to the BOR assessment. For participants who continue treatment beyond progression, the BOR was determined based on response assessments up to the time of initial RECIST 1.1 progression.

Other Outcome Measures:

1. Number of Participants With Death, Study Drug-Related Death, Serious Adverse Events (SAEs), and Study Drug-Related SAEs in All Treated Participants at Primary Endpoint [ Time Frame: Date of first dose of study drug to 30 days post last dose of study drug, approximately 18 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Inclusion Criteria:

• Men and women ≥ 18 years of age with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Histologically confirmed recurrent or metastatic SCCHN (oral cavity, pharynx, larynx), stage III/IV and not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy)
• Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant (ie with radiation after surgery), primary (ie, with radiation), recurrent, or metastatic setting
• Measurable disease by Computed tomography (CT) or Magnetic resonance imaging (MRI) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria

Exclusion Criteria:

• Active brain metastases or leptomeningeal metastases are not allowed
• Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary, and salivary gland or non-squamous histologies (eg: mucosal melanoma) are not allowed
• Subjects with active, known or suspected autoimmune disease

Contacts and Locations

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Sponsors and Collaborators

Bristol-Myers Squibb

Ono Pharmaceutical Co. Ltd

Investigators

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Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information  FDA Safety Alerts and Recalls  BMS Clinical Trial Patient Recruiting  Investigator Inquiry Form 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington KJ, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Docampo LCI, Haddad R, Rordorf T, Kiyota N, Tahara M, Lynch M, Jayaprakash V, Li L, Gillison ML. Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol. 2018 Jun;81:45-51. doi: 10.1016/j.oraloncology.2018.04.008. Epub 2018 Apr 17.

Kiyota N, Hasegawa Y, Takahashi S, Yokota T, Yen CJ, Iwae S, Shimizu Y, Hong RL, Goto M, Kang JH, Sum Kenneth Li W, Ferris RL, Gillison M, Namba Y, Monga M, Lynch M, Tahara M. A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator's choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141. Oral Oncol. 2017 Oct;73:138-146. doi: 10.1016/j.oraloncology.2017.07.023. Epub 2017 Sep 1.

Harrington KJ, Ferris RL, Blumenschein G Jr, Colevas AD, Fayette J, Licitra L, Kasper S, Even C, Vokes EE, Worden F, Saba NF, Kiyota N, Haddad R, Tahara M, Grünwald V, Shaw JW, Monga M, Lynch M, Taylor F, DeRosa M, Morrissey L, Cocks K, Gillison ML, Guigay J. Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1104-1115. doi: 10.1016/S1470-2045(17)30421-7. Epub 2017 Jun 23.

Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016 Nov 10;375(19):1856-1867. Epub 2016 Oct 8.

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Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT02105636 History of Changes
Other Study ID Numbers:	CA209-141; 2013-003622-86 ( EudraCT Number )
First Posted:	April 7, 2014
Results First Posted:	January 11, 2017
Last Update Posted:	August 2, 2018
Last Verified:	July 2018

Additional relevant MeSH terms:

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Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Nivolumab; Carcinoma; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Neoplasms by Site; Docetaxel; Methotrexate; Cetuximab; Antineoplastic Agents; Tubulin Modulators	Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents