Clinical Trials /

Nivolumab, Ipilimumab, and Radiation Therapy in Treating Patients With Stage III-IVB Head and Neck Cancer

NCT03162731

Description:

This pilot clinical trial studies the side effects of nivolumab, ipilimumab and radiation therapy in treating patients with stage IVA-B head and neck cancer. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving nivolumab, ipilimumab, and radiation therapy may work better in treating patients with stage IVA-B head and neck cancer.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab, Ipilimumab, and Radiation Therapy in Treating Patients With Stage III-IVB Head and Neck Cancer
  • Official Title: A Pilot Trial of Nivolumab and Ipilimumab in Combination With Radiotherapy in Patients With Locally Advanced Head and Neck Cancer; CA209-931

Clinical Trial IDs

  • ORG STUDY ID: 17P.082
  • NCT ID: NCT03162731

Conditions

  • Larynx
  • Lip, Oral Cavity and Pharynx

Interventions

DrugSynonymsArms
Nivolumab946414-94-4, BMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment ( nivolumab, ipilimumab, radiation therapy)
Ipilimumab477202-00-9, 720801, 732442, Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyTreatment ( nivolumab, ipilimumab, radiation therapy)

Purpose

This pilot clinical trial studies the side effects of nivolumab, ipilimumab and radiation therapy in treating patients with stage IVA-B head and neck cancer. Monoclonal antibodies, such as nivolumab and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving nivolumab, ipilimumab, and radiation therapy may work better in treating patients with stage IVA-B head and neck cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To investigate the safety of the combination of nivolumab and ipilimumab with radiation
      treatment for definitive management of patients with locally advanced squamous cell carcinoma
      of the head and neck.

      SECONDARY OBJECTIVES:

      I. To estimate the 1 year progression-free survival (PFS) in all patients treated.

      II. To assess the overall response rate and overall survival of patients at one year

      TERTIARY OBJECTIVES:

      I. To explore whether PDL1 expression is associated with treatment response. II. To explore
      whether there is a net change in the Th1/Th2 ratio (IFN-gamma, IL-4, IL10, etc) or cell
      subset frequencies (M2 monocytes, myeloid-derived suppressor cells, etc) within a patient's
      peripheral blood either at baseline or in response to treatment is associated with treatment
      response.

      III. To explore whether exosomes or other immune related serum biomarkers change after
      combination therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment ( nivolumab, ipilimumab, radiation therapy)ExperimentalPatients receive nivolumab IV over at least 30 minutes every 2 weeks and ipilimumab IV over at least 90 minutes every 6 weeks. Beginning week 3, patients undergo simultaneous integrated boost intensity modulated radiation therapy or volumetric modulated arc therapy for 5 days per week over 7 weeks. Patients continue nivolumab every 2 weeks for 12 doses and ipilimumab every 6 weeks for 4 doses. Courses repeat for up to 23 weeks in the absence of disease progression or unacceptable toxicity.
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be 18 years of age and older

          -  Pathologically confirmed squamous cell carcinoma of the head and neck (SCCHN), not
             previously treated

          -  Stage III-IVB disease of 1) oral cavity, 2) HPV-negative (p16-) oropharynx, 3) larynx,
             4) hypopharynx

          -  Oropharyngeal primaries that are HPV-mediated (p16+) must be stage II-III. Stage II
             pateints must be either N2 or, if T3N0 or T3N1 they must also have at least 20 pack
             year history of smoking

          -  Tumor sample must be available for HPV p16 and PD-L1 testing

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  White blood cells 2000/ul or more

          -  Absolute neutrophil count 1500/ul or more

          -  Platelets 100,000/ul or more

          -  Hemoglobin 9 g/dl or more

          -  Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with
             Gilbert syndrome, who can have total bilirubin < 3 mg/dl)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal
             to 3 x the upper limit of normal

          -  Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the
             Cockcroft-Gault formula or Serum creatinine less than or equal to 1.5 x upper limit of
             normal (ULN)

          -  Women of reproductive potential should have a negative serum or urine pregnancy test
             (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
             [HCG]) within 24 hours of the start of study drugs

          -  Women of reproductive potential must use highly effective contraception methods to
             avoid pregnancy for 23 weeks after the last dose of study drugs; "women of
             reproductive potential" 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 more than 40 mIU/mL

          -  Men of reproductive potential who are sexually active with women of reproductive
             potential must use any contraceptive method with a failure rate of less than 1% per
             year; men who are receiving the study medications will be instructed to adhere to
             contraception for 31 weeks after the last dose of study drugs; men who are azoospermic
             do not require contraception

          -  Informed consent: all subjects must be able to comprehend and sign a written informed
             consent document

        Exclusion Criteria:

          -  Primary nasopharyngeal carcinoma

          -  Patients with brain metastases

          -  Patients who have participated in a study with an investigational agent or device
             within 2 weeks of initiation of treatment

          -  Any prior radiotherapy to the neck

          -  Patients with known contraindications to radiotherapy, including inherited syndromes
             associated with hypersensitivity to ionizing radiation (e.g., Ataxia-Telangiectasia,
             Nijmegen Breakage Syndrome)

          -  Any prior chemotherapy or radiation therapy for the current diagnosis

          -  Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other
             antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint
             pathways

          -  Any history of a sever hypersensitivity reaction to any monoclonal antibody

          -  Any history of allergy to the study drug components

          -  Any concurrent malignancies- exceptions include- basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical
             cancer that has undergone potentially curative therapy; patients with a history of
             other prior malignancy must have been treated with curative intent and must have
             remained disease-free for 3 years post-diagnosis

          -  Any diagnosis of immunodeficiency or current immunosuppressive therapy including
             >10mg/day of prednisone within 14 days of enrollment is not permitted

          -  Patients that have an active autoimmune disease requiring systemic treatment within
             the past 3 months or a documented history of clinically severe autoimmune disease, or
             a syndrome that requires systemic steroids (> 10 mg daily prednisone equivalents) or
             immunosuppressive agents; subjects with vitiligo, type I diabetes mellitus, or
             resolved childhood asthma/atopy would be an exception to this rule. Inhaled or topical
             steroids, and adrenal replacement steroids </=10mg daily prednisone equivalent, are
             permitted in the absence of active autoimmune disease. Subjects with hypothyroidism
             stable on hormone replacement or Sjorgen's syndrome will not be excluded from the
             study

          -  Patients with evidence of interstitial lung disease or active, non-infectious
             pneumonitis

          -  Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) or
             acquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis B
             surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV]
             ribonucleic acid [RNA] [qualitative] is detected)

          -  Patients who have received a live vaccine within 30 days prior to the radiation
             therapy

          -  Patients must not be receiving any other investigational agents

          -  Patients with uncontrolled intercurrent illnesses including, but not limited to an
             active infection requiring systemic therapy or a known psychiatric or substance abuse
             disorder(s) that would interfere with cooperation with the requirements of the trial

          -  Women must not be pregnant (as above) or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events version 4.03
Time Frame:Up to 6 months
Safety Issue:
Description:There will be continuous monitoring of the incidence of grade 3-5 toxicities.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Sidney Kimmel Cancer Center at Thomas Jefferson University

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