Chemotherapy, Nivolumab, and Intensity-Modulated Radiation Therapy in Treating Patients with Stage III-IV Laryngeal or Hypopharyngeal Cancer

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Status: Active

Description

This phase II trial studies how well chemotherapy, nivolumab, and intensity-modulated radiation therapy work in treating patients with stage III-IV laryngeal or hypopharyngeal cancer. Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Giving chemotherapy with nivolumab and intensity-modulated radiation therapy may work better in treating patients with laryngeal and hypopharyngeal cancer than standard of care chemotherapy and radiation therapy.

Eligibility Criteria

Inclusion Criteria

  • Subject must have histologically or cytologically confirmed, resectable or unresectable, stage III or stage IV locoregionally advanced squamous cell carcinoma of the larynx or hypopharynx, as defined by 2017 American Joint Committee on Cancer (AJCC), 8th edition
  • Willing to provide tissue from diagnostic biopsy and blood samples before, during, and after treatment
  • Any smoking history is permitted
  • Patients must have human papillomavirus (HPV) negative disease. Those patients with a supraglottic primary are required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory HPV polymerase chain reaction (PCR) or in situ hybridization staining (ISH) testing to rule out oropharyngeal origin with laryngeal extension
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 80%)
  • Leukocytes >= 3,000/mcL (within 21 days prior to study registration)
  • Absolute neutrophil count >= 1,500/mcL (within 21 days prior to study registration)
  • Platelets >= 100,000/mcL (within 21 days prior to study registration)
  • Total bilirubin =< 2.0 g/dL (within 21 days prior to study registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine transferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (within 21 days prior to study registration)
  • Creatinine within normal institutional limits (within 21 days prior to study registration) OR
  • Creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal (within 21 days prior to study registration)
  • Ability to understand and the willingness to sign a written informed consent document
  • Women of childbearing potential (WOCBP) must agree to use appropriate method(s) of contraception. WOCBP should plan to use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
  • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 iu/l or equivalent units of human chorionic gonadotropin [hcg]) within 24 hours prior to the start of nivolumab * “Women of childbearing potential (WOCBP)” is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
  • Men who are sexually active with WOCBP must agree to use any contraceptive method with a failure rate of less than 1% per year. Men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception

Exclusion Criteria

  • Existing severe autoimmune conditions (at the discretion of the treating physician). Patients with a history of Hashimoto thyroiditis who are stable on replacement hormone therapy are not excluded. Short-term corticosteroid dosing is permitted (i.e. dexamethasone for chemotherapy-induced nausea prevention during induction chemotherapy) as long as steroids are discontinued within 1 week (7 days) of receiving the first dose of nivolumab during the induction phase of treatment
  • Subject who has had prior chemotherapy for head and neck cancer and/or radiotherapy to the head and neck
  • Subject who has been treated with immunotherapy. This includes prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Known human immunodeficiency virus carrier or a diagnosis of immunodeficiency. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., hepatitis B surface antigen (HBsAg, Australia antigen) positive, or hepatitis C antibody (anti-HCV) positive (except if hepatitis C virus [HCV]-ribonucleic acid [RNA] negative)
  • Known non-infectious pneumonitis or any history of interstitial lung disease
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, and low-risk prostate adenocarcinoma being managed with active surveillance. A history of another separate malignancy in remission without evidence of active disease in the last 5 years is permitted

Locations & Contacts

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: Active
Contact: Robert I. Haddad
Email: RIHADDAD@PARTNERS.ORG

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To improve efficacy with respect to laryngectomy-free survival (LFS) at 2-years from time of study registration as the primary endpoint.

SECONDARY OBJECTIVES:

I. To evaluate clinicopathologic and radiologic response.

II. To estimate overall survival (OS).

III. To estimate laryngo-esophageal dysfunction-free survival (LEDFS).

IV. To evaluate safety and toxicity, and quality of life scores.

V. To characterize distinct tumor immunophenotypes and correlate these findings with outcomes.

OUTLINE:

INDUCTION THERAPY: Patients receive docetaxel intravenously (IV), cisplatin IV, and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients with partial response (PR) or complete response (CR) proceed with Concurrent Immunoradiotherapy.

CONCURRENT IMMUNORADIOTHERAPY: Within 42 days of Induction Therapy completion, patients undergo 33-35 fractions of intensity-modulated radiation therapy (IMRT) Monday-Friday for up to 7 weeks. Patients also receive nivolumab IV over 30 minutes beginning between days 1 and 7. Treatment repeats every 14 days for up to 3 or 4 doses in the absence of disease progression or unacceptable toxicity.

ADJUVANT THERAPY: Within 3-8 weeks of IMRT completion, patients receive nivolumab IV over 30 minutes. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 4 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Robert I. Haddad

Trial IDs

Primary ID 18-652
Secondary IDs NCI-2019-04114
Clinicaltrials.gov ID NCT03894891