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A Study of Pembrolizumab (MK-3475) for First Line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (MK-3475-048/KEYNOTE-048)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02358031
First received: February 3, 2015
Last updated: March 16, 2017
Last verified: March 2017
  Purpose
Participants with recurrent or metastatic (R/M) squamous cell cancer of the head and neck (HNSCC) will be randomly assigned to receive pembrolizumab alone, or pembrolizumab + a platinum-based drug (cisplatin or carboplatin) + 5-Fluorouracil (5-FU), or cetuximab + a platinum-based drug (cisplatin or carboplatin) + 5-FU. The primary study hypothesis is that pembrolizumab or pembrolizumab in combination with chemotherapy prolongs progression free survival and overall survival compared to standard treatment.

Condition Intervention Phase
Recurrent Head and Neck Cancer Metastatic Head and Neck Cancer Biological: Pembrolizumab Drug: Cisplatin Drug: Carboplatin Drug: 5-FU Biological: Cetuximab Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase 3 Clinical Trial of Pembrolizumab (MK-3475) in First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Programmed Cell Death Ligand 1 (PDL1)-Positive Expression [ Time Frame: Up to 3 Years ]
  • Overall Survival in Participants With PDL1-Postive Expression [ Time Frame: Up tp 5 Years ]
  • PFS per RECIST 1.1 by BICR in All Participants [ Time Frame: Up to 3 Years ]
  • Overall Survival in All Participants [ Time Frame: Up to 5 Years ]

Secondary Outcome Measures:
  • PFS at 6 Months per RECIST 1.1 by BICR [ Time Frame: Up to 6 Months ]
  • Objective Response Rate per RECIST 1.1 by BICR [ Time Frame: Up to 3 Years ]
  • PFS at 12 Months per RECIST 1.1 by BICR [ Time Frame: Up to 12 Months ]
  • Time to Deterioration in Quality of Life Global Health Status/Quality of Life Scales of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Score for Items 29 and 30 [ Time Frame: Up to 3 Years ]

Estimated Enrollment: 825
Study Start Date: March 2015
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pembrolizumab
Participants receive pembrolizumab 200 mg, intravenously (IV) on Day 1 of each week in 3-week cycles for up to 24 months.
Biological: Pembrolizumab
Other Name: MK-3475
Experimental: Pembrolizumab + Platinum + 5-FU
Participants receive pembrolizumab 200 mg, intravenously (IV) on Day 1 of each week in 3-week cycles for up to 24 months; plus cisplatin 100 mg/m^2 IV or carboplatin AUC 5 IV (Investigator's choice) on Day 1 of each week in 3-week cycles (6 cycle maximum); plus 5-FU 1000 mg/m^2/day IV continuous from Day 1-4 of each 3- week cycle (6 cycle maximum).
Biological: Pembrolizumab
Other Name: MK-3475
Drug: Cisplatin Drug: Carboplatin Drug: 5-FU
Active Comparator: Cetuximab + Platinum + 5FU
Participants receive cetuximab on Day 1 at a dose of 400 mg/m^2 IV, and then 250 mg/m^2 IV on Day 1 of each week until disease progression or unacceptable toxicity; plus cisplatin 100 mg/m^2 IV or carboplatin AUC 5 IV (Investigator's choice) on Day 1 of each week in 3-week cycles (6 cycle maximum for platinum-based therapy); plus 5-FU 1000 mg/m^2/day IV continuous from Day 1-4 of each 3-week cycle (6 cycle maximum).
Drug: Cisplatin Drug: Carboplatin Drug: 5-FU Biological: Cetuximab

  Eligibility

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

Inclusion Criteria:

  • Histologically- or cytologically-confirmed recurrent or metastatic head and neck squamous cell carcinoma considered incurable by local therapies
  • No prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed > 6 months prior if given as part of multimodal treatment for locally advanced disease)
  • Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology)
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate organ function
  • Can provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate is not sufficient): A newly obtained biopsy (within 90 days prior to start of study treatment) is preferred but an archival sample is acceptable.
  • Have results from testing of HPV status for oropharyngeal cancer
  • Female participants of childbearing potential should have a negative pregnancy test and must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 180 days after the last dose of study medication
  • Male participants must agree to use an adequate method of contraception starting with the first dose of study medication through 180 days after the last dose of study medication

Exclusion Criteria:

  • Disease suitable for local therapy administered with curative intent
  • Has progressive disease (PD) within six (6) months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC
  • Radiation therapy (or other non-systemic therapy) within 2 weeks prior to randomization or not fully recovered from adverse events due to a previously administered treatment
  • Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks of the first dose of study medication
  • Life expectancy of <3 months and/or has rapidly progressing disease
  • Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication (physiologic doses of corticosteroids may be approved after consultation with the Sponsor)
  • Diagnosed and/or treated additional malignancy within 5 years prior to randomization with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers
  • Has had an allogeneic tissue/solid organ transplant
  • Active central nervous system metastases and/or carcinomatous meningitis
  • Active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy is not considered a form of systemic treatment
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Active infection requiring systemic therapy
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of study medication
  • Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or previously participated in Merck MK-3475 clinical trial
  • Known history of human immunodeficiency virus (HIV)
  • Known active Hepatitis B or C
  • Received a live vaccine within 30 days of planned start of study medication
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02358031

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02358031     History of Changes
Other Study ID Numbers: 3475-048
2014-003698-41 ( EudraCT Number )
Study First Received: February 3, 2015
Last Updated: March 16, 2017

Keywords provided by Merck Sharp & Dohme Corp.:
PD-1
PD-L1

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Pembrolizumab
Cisplatin
Cetuximab
Carboplatin
Antineoplastic Agents

ClinicalTrials.gov processed this record on June 27, 2017