Clinical Trials /

Induction TPN Followed by Nivolumab With Radiation in Locoregionally Advanced Laryngeal and Hypopharyngeal Cancer

NCT03894891

Description:

This research is being performed to treat patient for head and neck cancer patients who have not received prior chemotherapy.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Induction TPN Followed by Nivolumab With Radiation in Locoregionally Advanced Laryngeal and Hypopharyngeal Cancer
  • Official Title: Sequential Therapy With Induction TPN Followed by Nivolumab With Radiation in Locoregionally Advanced Laryngeal and Hypopharyngeal Cancer

Clinical Trial IDs

  • ORG STUDY ID: 18-652
  • NCT ID: NCT03894891

Conditions

  • Head and Neck Cancer

Interventions

DrugSynonymsArms
NivolumabOPDIVO®Docetaxel+Cisplatin+Nivolumab+Radioimmunotherapy
CisplatinPlatinolDocetaxel+Cisplatin+Nivolumab+Radioimmunotherapy
DocetaxelTaxotereDocetaxel+Cisplatin+Nivolumab+Radioimmunotherapy

Purpose

This research is being performed to treat patient for head and neck cancer patients who have not received prior chemotherapy.

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug or combination of interventions is
      being studied.

      Nivolumab is approved by the U.S. Food and Drug Administration (FDA) for the treatment of
      recurrent or advanced head and neck cancer (head and neck cancer that has come back or is
      incurable) but is considered investigational for head and neck cancer patients who have not
      received prior chemotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
Docetaxel+Cisplatin+Nivolumab+RadioimmunotherapyExperimentalDocetaxel will be administered per standard institutional every 3 weeks Nivolumab will be administered intravenously every 3 weeks Cisplatin will be administered intravenously every 3 weeks Radioimmunotherapy will be conducted 3 weeks after the last cycle of TPN (docetaxel, cisplatin and nivolumab)
  • Nivolumab
  • Cisplatin
  • Docetaxel

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 HPV negative disease. Those patients with a supraglottic primary
             are required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory
             HPV PCR or ISH testing to rule out oropharyngeal origin with laryngeal extension

          -  Age 18 years or older

          -  ECOG performance status ≤ 1 (Karnofsky ≥ 80%, see Appendix A)

          -  Participant must have normal organ and marrow function as defined below within 21 days
             prior to study registration:

               -  leukocytes ≥3,000/mcL

               -  absolute neutrophil count ≥1,500/mcL

               -  platelets ≥100,000/mcL

               -  total bilirubin ≤2.0 g/dL

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

               -  creatinine within normal institutional limits OR

               -  creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
                  above institutional normal

          -  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 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 (ie, 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 HCV-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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Laryngectomy-free survival
Time Frame:2 years
Safety Issue:
Description:To improve efficacy with respect to laryngectomy-free survival (LFS) at 2-years from time of study registration as the primary endpoint.

Secondary Outcome Measures

Measure:Quality of life Measure, QLQ-C30
Time Frame:2 years
Safety Issue:
Description:General "Quality of Life" or QOL will be assessed via a self-reported questionnaire at the timepoints outlined in the Study Calendar. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) contains 30 questions belonging to five functional scales, nine symptom scales, financial difficulty, and one global health status (quality of life) scale. The responses are graded on a scale of 1 to 4, where 1 is "not at all" and 4 is "very much".
Measure:Quality of life Measure, QLQ-H&N35
Time Frame:2 years
Safety Issue:
Description:"Quality of Life" or QOL specifically related to head and neck cancer will be assessed via a self-reported questionnaire at the timepoints outlined in the Study Calendar. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-H&N35) will be used to evaluate the reliability and validity of a new, disease-specific quality of life measure for patients with head and neck cancer: This questionnaire contains 35 questions with responses on a scale of 1 to 4, where 1 is "not at all" and 4 is "very much".
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Overall Survival (OS) is defined as the time from study registration to death due to any cause, otherwise, participants are censored at date last known alive.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Head and Neck Cancer

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