Clinical Trials /

Trial of Ibrutinib Combined With Nivolumab or Cetuximab to Treat Recurrent/Metastatic HNSCC

NCT03646461

Description:

This is an open-label, randomized, phase II trial to test the efficacy of Ibrutinib in combination with either Nivolumab or Cetuximab in the treatment of recurrent and/or metastatic head an neck squamous cell carcinoma

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial of Ibrutinib Combined With Nivolumab or Cetuximab to Treat Recurrent/Metastatic HNSCC
  • Official Title: A Multi-Institutional, Open-Label, Randomized, Phase II Trial Of Ibrutinib In Combination With EGFR Inhibition Or PD-1 Inhibition In Patients With Recurrent/Metastatic Head And Neck Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 161755
  • NCT ID: NCT03646461

Conditions

  • Head and Neck Cancer
  • Squamous Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
Ibrutinib 560mg PO daily (Imbruvica)ImbruvicaArm A: Ibrutinib + Cetuximab
CetuximabErbituxArm A: Ibrutinib + Cetuximab
NivolumabopdivoArm B: Ibrutinib + Nivolumab

Purpose

This is an open-label, randomized, phase II trial to test the efficacy of Ibrutinib in combination with either Nivolumab or Cetuximab in the treatment of recurrent and/or metastatic head an neck squamous cell carcinoma

Detailed Description

      Open-label, randomized, controlled, clinical trial. Enrollment will be stratified by HPV
      status and randomized in a 1:1 ratio to either ibrutinib + cetuximab or ibrutinib + nivolumab

      The study will enroll patients who develop R/M HNSCC have not yet been treated with EGFR
      inhibitors in the recurrent/metastatic setting. All patients being considered for the study
      must be ≥ 18 years of age and will receive: i) ibrutinib + cetuximab or ii) ibrutinib +
      nivolumab.

      To determine the clinical efficacy of ibrutinib in combination with cetuximab or nivolumab in
      patients with R/M HNSCC.

      Ibrutinib will be supplied by Pharmacyclics as 140 mg hard gelatin capsules for oral (PO)
      administration.

      Cetuximab will be supplied as a clear, colorless liquid formulated for intravenous
      administration.

      Nivolumab will be supplied as a clear, colorless liquid formulated for intravenous
      administration.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: Ibrutinib + CetuximabExperimentalIbrutinib 560mg PO daily (Imbruvica) PLUS Cetuximab 400mg/m2 x 1 then 250 mg/m2 weekly 28 day cycle
  • Ibrutinib 560mg PO daily (Imbruvica)
  • Cetuximab
Arm B: Ibrutinib + NivolumabExperimentalIbrutinib 560mg PO daily (Imbruvica) PLUS Nivolumab 3mg/kg biweekly 28 day cycle
  • Ibrutinib 560mg PO daily (Imbruvica)
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

        - To be enrolled in the study, each potential subject must satisfy all of the following
        inclusion criteria.

          1. Histologically or cytologically proven squamous cell carcinoma of the head and neck
             not amenable to curative intent therapy. P16 or HPV status must be known on all
             patients with oropharyngeal primaries or unknown primaries.

          2. Known p16 and/or HPV status by institutional standard.

          3. Presence of measurable tumor lesions per RECIST criteria v1.1 by investigator review

          4. Life expectancy greater than 12 weeks

          5. Previously archived or newly obtained tumor specimens for correlative analysis

          6. Adequate hematologic function independent of transfusion and growth factor support for
             at least 7 days prior to screening and randomization, with the exception of pegylated
             G-CSF (pegfilgrastim) and darbepoetin which require at least 14 days prior to
             screening and randomization defined as:

               -  Absolute neutrophil count >750 cells/mm3 (0.75 x 109/L).

               -  Platelet count >50,000 cells/mm3 (50 x 109/L).

               -  Hemoglobin >8.0 g/dL.

          7. Adequate hepatic and renal function defined as:

               -  Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper
                  limit of normal (ULN).

               -  Estimated Creatinine Clearance ≥30 ml/min (Cockcroft-Gault)

               -  Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of
                  non-hepatic origin)

          8. PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN

          9. Men and women ≥ 18 years of age.

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

         11. Female subjects who are of non-reproductive potential (ie, post-menopausal by history
             - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal
             ligation; OR history of bilateral oophorectomy). Female subjects of childbearing
             potential must have a negative serum pregnancy test upon study entry.

         12. Male and female subjects who agree to use highly effective methods of birth control
             (eg, , implants, injectables, combined oral contraceptives, some intrauterine devices
             [IUDs], complete abstinence, or sterilized partner) and a barrier method (eg.,
             condoms, vaginal ring, sponge, etc) during the period of therapy and for for 30 days
             after the last dose of study drug for females and 90 days for males.Ability and
             willingness to provide written informed consent

        Exclusion Criteria:

        - To be enrolled in the study, potential subjects must meet NONE of the following exclusion
        criteria:

          1. Prior therapy with an EGFR inhibitor in the recurrent or metastatic setting

          2. Nasopharyngeal carcinoma histology

          3. Known, clinically active central nervous system metastases (stable metastases
             permitted)

          4. Chemotherapy ≤ 28 days prior to first administration of study treatment and/or
             monoclonal antibody (including immunotherapy) ≤16 weeks prior to first administration
             of study treatment.

          5. Prior exposure to BTK inhibitor, PD-1 inhibitor, or PD-L1 inhibitor

          6. History of other malignancies, except:

               -  Malignancy treated with curative intent and with no known active disease present
                  for ≥3 years before the first dose of study drug and felt to be at low risk for
                  recurrence by treating physician.

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease.

               -  Adequately treated carcinoma in situ without evidence of disease.

          7. Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc.,
             or chronic administration [>14 days] of >10 mg/day of prednisone) within 28 days of
             the first dose of study drug.

          8. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.

          9. Recent infection requiring systemic treatment that was completed ≤14 days before the
             first dose of study drug.

         10. Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved
             to Common Terminology Criteria for Adverse Event (CTCAE v4.0), Grade ≤1, or to the
             levels dictated in the inclusion/exclusion criteria with the exception of alopecia.

         11. Known bleeding disorders (eg, von Willebrand's disease) or hemophilia.

         12. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

         13. Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus
             (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core
             antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative
             polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive
             will be excluded.

         14. Any uncontrolled active systemic infection.

         15. Any history of interstitial lung disease.

         16. Active autoimmune disease or other contraindication to PD-1 inhibition.

         17. Major surgery within 4 weeks of first dose of study drug.

         18. Any life-threatening illness, medical condition, or organ system dysfunction that, in
             the investigator's opinion, could compromise the subject's safety or put the study
             outcomes at undue risk.

         19. Currently active, clinically significant cardiovascular disease, such as uncontrolled
             arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart
             Association Functional Classification; or a history of myocardial infarction, unstable
             angina, or acute coronary syndrome within 6 months prior to randomization.

         20. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting
             gastrointestinal function, or resection of the stomach or small bowel, symptomatic
             inflammatory bowel disease or ulcerative colitis, or partial or complete bowel
             obstruction.

         21. Concomitant use of warfarin or other Vitamin K antagonists.

         22. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor

         23. Currently active, clinically significant hepatic impairment Child-Pugh Class B or C
             according to the Child-Pugh Classification

         24. Lactating or pregnant.

         25. Unwilling or unable to participate in all required study evaluations and procedures.

         26. Unable to understand the purpose and risks of the study and to provide a signed and
             dated informed consent form (ICF) and authorization to use protected health
             information (in accordance with national and local subject privacy regulations).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical Efficacy of Combined Therapies using RECIST v1.1
Time Frame:3 yrs
Safety Issue:
Description:The primary endpoint is the clinical efficacy of each combinatorial treatment regimen as defined by the best overall response rate (proportion of patients with a partial or complete response in tumor burden) using RECIST v1.1

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:3 yrs
Safety Issue:
Description:Progression-free survival (PFS), defined as the interval from the date of first dose of ibrutinib to disease progression or death from any cause
Measure:Overall Survival
Time Frame:3 yrs
Safety Issue:
Description:Overall survival (OS), defined as the date of first dose of ibrutinib to the date of death from any cause.
Measure:Duration of Response
Time Frame:3 yrs
Safety Issue:
Description:Duration of response is measured from the time measurement criteria are met for complete response or partial response (whichever is recorded) until the first date that recurrent or progressive is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started)
Measure:Safety as assessed by the frequency of adverse events per CTCAE v4.0
Time Frame:3 yrs
Safety Issue:
Description:Overall frequency and severity of adverse events per CTCAE v4.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, San Diego

Trial Keywords

  • oropharyngeal

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