Clinical Trials /

Safety Testing of Adding Nivolumab to Chemotherapy in Patients With Intermediate and High-Risk Local-Regionally Advanced Head and Neck Cancer

NCT02764593

Description:

This study will evaluate the safety of adding nivolumab to several chemotherapy platforms with weekly cisplatin, high-dose cisplatin, cetuximab or radiation therapy alone.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title:Chemotherapy +/- Nivolumab in Patients With Intermediate and High-Risk Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma
  • Official Title:Randomized Phase III Trial Of Cisplatin-Based Chemotherapy (CRT) +/- Nivolumab (Anti-PD-1) In Patients With Intermediate And High-Risk Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma (With Phase I Lead In)

Clinical Trial IDs

  • ORG STUDY ID: RTOG 3504
  • SECONDARY ID: RF 3504
  • SECONDARY ID: CA209-410
  • NCT ID: NCT02764593

Trial Conditions

  • Head and Neck Squamous Cell Carcinoma (HNSCC)

Trial Interventions

DrugSynonymsArms
NivolumabOpdivoArm 1 (Nivolumab + Cisplatin)
CisplatinPlatinolArm 1 (Nivolumab + Cisplatin)
CetuximabErbituxArm 3 (Nivolumab + Cetuximab)

Trial Purpose

This phase III trial with a phase I dose finding lead-in study will evaluate whether the addition of nivolumab will improve the overall survival for patients with newly diagnosed intermediate-risk or high-risk Head and Neck Squamous Cell Carcinoma (HNSCC) when treated with radiation therapy and cisplatin-based or cetuximab-based chemotherapy or with radiation alone.

Detailed Description

This study is designed to evaluate whether nivolumab (anti-PD-1 targeted immunotherapy) will improve overall survival (OS) for patients with newly diagnosed intermediate-risk or high-risk HNSCC when treated with cisplatin-based or cetuximab-based CRT or radiation alone. The study is comprised of a phase I safety lead in portion followed by a phase III portion in which patients with newly diagnosed, local-regionally advanced HNSCC (stage III/IV) will be randomized into a placebo-controlled, double-blind clinical trial of nivolumab, cisplatin and IMRT vs. placebo, cisplatin and IMRT.

Trial Arms

NameTypeDescriptionInterventions
Arm 1 (Nivolumab + Cisplatin)ExperimentalPatients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. Cisplatin will be given weekly. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
  • Nivolumab
  • Cisplatin
    Arm 2 (Nivolumab + High-dose Cisplatin)ExperimentalPatients will receive Nivolumab via IV administration starting 14 days prior to IMRT, then Day 1 of IMRT and then every 21 days for 6 doses. Cisplatin will be given every 21 days for 3 doses. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
    • Nivolumab
    • Cisplatin
      Arm 3 (Nivolumab + Cetuximab)ExperimentalPatients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. Cetuximab will be given for 7 doses. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
      • Nivolumab
        • Cetuximab
        Arm 4 (Nivolumab + IMRT)ExperimentalPatients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
        • Nivolumab

          Eligibility Criteria

          Inclusion Criteria: Phase I

          - Histologically or cytologically-confirmed diagnosis of HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx.

          - Group 1: Oropharynx cancer that is p16-positive by immunohistochemistry with smoking status > 10 Pack-years, stage T2 N2b-N3 or T3-4 N0-3 OR ≤ 10 pack-years, stage T4N0-N3 or T2-T3N2c-N3.

          - Group 2: Oral cavity, larynx, hypopharynx, or p16-negative oropharynx cancer, stage T2 N2a-N3 or T3-4 N0-3 based on the following diagnostic workup:

          - Mandatory submission of H&E and p16 stained slides and (or punch biopsy of paraffin block) for central review of p16 staining is required for oropharyngeal patients and for PD-L1 expression analysis for all patients

          - History/physical examination within 28 days prior to registration

          - Examination by Radiation Oncologist, Medical Oncologist, and Ear, Nose, Throat (ENT) or Head & Neck Surgeon within 28 days prior to registration

          - Fiberoptic exam with laryngopharyngoscopy within 28 days prior to registration

          - Diagnostic quality CT or MRI of neck, with contrast, within 28 days prior to registration; a 18-F-FDG-PET/CT of the neck only is acceptable as a substitute if the CT is of diagnostic quality and with IV contrast.

          - Age ≥ 18 years

          - The trial is open to both genders

          Exclusion Criteria:

          - Definitive clinical or radiologic evidence of distant (beyond cervical lymph node and neck tissue) metastatic disease.

          - Patients with oral cavity cancer are excluded from participation if resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist.

          - Carcinoma of the neck of unknown primary site origin (even if p16-positive).

          - Absence of RECIST, v. 1.1 defined measurable disease.

          - Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. Patients with RECIST, v. 1.1 evaluable remaining cancer either in the neck or primary site remain eligible.

          - Simultaneous primary cancers or separate bilateral primary tumor sites.

          - Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).

          - Prior systemic chemotherapy for the study cancer.

          - Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.

          - Patients with active autoimmune disease, with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism and psoriasis.

          - Use of systemic corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, with exception of inhaled or topical steroids.

          - Known immunosuppressive disease, for example HIV infection or history of bone marrow transplant or chronic lymphocytic leukemia (CLL).

          Maximum Eligible Age:N/A
          Minimum Eligible Age:18 Years
          Eligible Gender:Both
          Healthy Volunteers:No

          Primary Outcome Measures

          Measure:Dose Limiting Toxicity (DLT)
          Time Frame:From the first dose of nivolumab to 28 days after the completion of radiation therapy.
          Safety Issue:Yes
          Description:A nivolumab attributable, dose-limiting toxicity (DLT) will be defined as follows: 1) Any ≥ grade 3 adverse event (CTCAE, v. 4) that is related to nivolumab that does not resolve to grade 1 or less within 28 days; 2) A delay in radiotherapy of > 2 weeks due to toxicity related to nivolumab; 3) Inability to complete radiotherapy due to toxicity related to nivolumab; 4) Inability to receive an adequate dose (≥ 70%) of cisplatin (Arm 1 and 2) or cetuximab (Arm 3) due to toxicity definitely related to nivolumab.

          Secondary Outcome Measures

          Trial Keywords

          • Head and Neck Squamous Cell Carcinoma
          • HNSCC
          • Nivolumab