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Study To Compare Avelumab In Combination With Standard of Care Chemoradiotherapy (SoC CRT) Versus SoC CRT for Definitive Treatment In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (JAVELIN HEAD AND NECK 100)

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ClinicalTrials.gov Identifier: NCT02952586
Recruitment Status : Recruiting
First Posted : November 2, 2016
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This is a phase 3 randomized, placebo controlled study to evaluate the safety and anti-tumor activity of Avelumab in combination with standard of care chemoradiation (SoC CRT) versus SoC CRT alone in front-line treatment of patients with locally advanced head and neck cancer.

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Head and Neck Drug: Avelumab Other: Chemoradiation Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 640 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-blind Phase 3 Study Of Avelumab In Combination With Standard Of Care Chemoradiotherapy (Cisplatin Plus Definitive Radiation Therapy) Versus Standard Of Care Chemoradiotherapy In The Front-line Treatment Of Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck
Actual Study Start Date : November 28, 2016
Estimated Primary Completion Date : April 8, 2021
Estimated Study Completion Date : May 18, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Avelumab + SOC Chemoradiation Therapy
  • Avelumab 10 mg/kg IV: Day 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; and Q2W for 12 months during the Maintenance Phase
  • Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase
  • Intensity Modulated Radiation Therapy (IMRT) 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase
Drug: Avelumab
Avelumab + SOC Chemoradiation

Placebo Comparator: Placebo + SOC CRT
  • Placebo IV matching avelumab: Days 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; Q2W for 12 months during the Maintenance Phase
  • Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase
  • IMRT 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase
Other: Chemoradiation
Cisplatin + Radiation Therapy




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Baseline up to 49 months ]
    PFS per modified Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Baseline up to 103 months ]
  2. Trough plasma concentration (Ctrough) of avelumab [ Time Frame: Lead-in Day 1; and Days 8 and 25 of CRT phase ]
    Ctrough is defined as the trough plasma concentration of avelumab

  3. Percentage of patients with positive anti-drug antibodies (ADA) and neutralizing antibodies [ Time Frame: Day 1 of the Lead-in Phase, and Days 8, and 25 of the CRT Phase ]
  4. Tumor tissue biomarker status [ Time Frame: Lead-in Day 1 ]
    Tumor tissue biomarkers including, but not limited to PD-L1 expression and tumor-infiltrating CD8+ T-lymphocytes.

  5. Maximum plasma concentration (Cmax) of Avelumab [ Time Frame: Lead-in Day 1; and Days 8 and 25 of CRT phase ]
  6. Area under the concentration-time curve extrapolated to infinity (AUCinf) for cisplatin [ Time Frame: Day 1 of CRT phase ]
  7. Cmax of Cisplatin [ Time Frame: Day 1 of CRT phase ]
  8. Clearance (CL) of cisplatin [ Time Frame: Day 1 of CRT phase ]
  9. Time to maximum plasma concentration (Tmax) and elimination half-life (t1/2)for cisplatin [ Time Frame: Day 1 of CRT phase ]
  10. Volume of distribution (Vz) for cisplatin (total and free) [ Time Frame: Day 1 of CRT phase ]
  11. Change from Baseline in the EuroQoL Group 5-Dimension 5- Level Self-Report Questionnaire (EQ-5D-5L) [ Time Frame: Lead-in Day 1 and CRT phase Day 1 and Day 29 ]
  12. Change from baseline in National Cancer Comprehensive Network (NCCN) Head and Neck Symptom Index-22 items (FHNSI-22) [ Time Frame: Lead-in Day 1 and CRT phase Day 1 and Day 29 ]
  13. Rate of pathologic complete response [ Time Frame: Baseline up to 49 months ]
    In any patients with resected specimens, neck dissection.

  14. Locoregional tumor control [ Time Frame: Baseline up to 49 months ]
    Per modified RECIST v1.1

  15. Distant metastatic failure [ Time Frame: Baseline up to 49 months ]
    Per modified RECIST v1.1

  16. Objective Response Rate - Percentage of Participants With Objective Response [ Time Frame: Baseline up to 49 months ]
    Per modified RECIST v1.1

  17. Duration of response [ Time Frame: Baseline up to 49 months ]
    Per modified RECIST v1.1

  18. The incidence of pathologically-positive neck dissection versus the incidence of pathologically-negative neck dissection [ Time Frame: Baseline up to 49 months ]


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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

INCLUSION CRITERIA

  • Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
  • HPV negative disease, Stage III, IVa, IVb; non-oropharyngeal HPV positive disease Stage III, IVa, IVb, HPV positive oropharyngeal disease T4 or N2c or N3
  • No prior therapy for advanced stage SCCHN; eligible for definitive CRT with curative intent.
  • Available tumor samples for submission or willing to undergo further tumor biopsies:
  • Age ≥18 years (≥19 in Korea;20 years in Japan and Taiwan).
  • ECOG Performance Status 0 or 1
  • Adequate bone marrow function
  • Adequate renal function
  • Adequate liver function
  • Pregnancy test (for patients of childbearing potential) negative at screening

EXCLUSION CRITERIA

  • Prior immunotherapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways.
  • Major surgery 4 weeks prior to randomization.
  • Prior malignancy requiring tumor-directed therapy within the last 2 years prior to enrollment, or concurrent malignancy associated with clinical instability. Exceptions for disease within the 2 years are superficial esophageal cancer (TIS or T1a) fully resected by endoscopy, prostate cancer (Gleason score 6) either curatively treated or deemed to not require treatment, ductal IS carcinoma of the breast that has completed curative treatment, adequately treated basal cell or squamous cell skin cancer.
  • Active autoimmune disease
  • Any of the following in the 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
  • Active infection requiring systemic therapy.
  • Use of immunosuppressive medication at time of randomization
  • Prior organ transplantation including allogenic stem-cell transplantation.
  • Diagnosis of prior immunodeficiency or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Vaccination within 4 weeks prior to randomization.
  • Current use of or anticipated need for treatment with other anti-cancer drugs.
  • Pregnant female patients, breastfeeding female patients, and male patients able to father children and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 60 days after the last dose of avelumab/placebo (whichever is later).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02952586


Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

  Show 439 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02952586     History of Changes
Other Study ID Numbers: B9991016
2016-001456-21 ( EudraCT Number )
LOCALLY ADVANCED HEAD AND NECK ( Other Identifier: Alias Study Number )
First Posted: November 2, 2016    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cisplatin
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs