Clinical Trials /

Abemaciclib + Nivolumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed or Recurred Within Six Months After Platinum-based Chemotherapy

NCT03655444

Description:

In phase I of the trial, the investigators aim to explore the safety and feasibility of abemaciclib in combination with nivolumab in patients with recurrent/metatstatic head and neck squamous cell carcinoma (RM-HNSCC). A dose de-escalation study design will be used to determine the recommended phase II dose (RP2D) of abemaciclib given with the standard dose of nivolumab. In phase II of the trial, the investigators aim to determine if abemaciclib and nivolumab will improve the one year survival from 36% (historical comparison with nivolumab) to 60% (abemaciclib + nivolumab) in patients with RM-HNSCC that had progressed or recurred within six months after platinum-based chemotherapy. Patients will be treated with abemaciclib at the recommended phase 2 dose (RP2D) in combination with standard doses of nivolumab. If this aim is met, genome sequencing, bulk and single cell RNAseq, and selected protein expression and deep cellular phenotyping will be performed on tumor tissue and blood obtained before and during treatment with abemaciclib and nivolumab. These biomarker data will be correlated with survival and tumor response to abemaciclib and nivolumab.

Related Conditions:
  • Head and Neck Neuroendocrine Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abemaciclib + Nivolumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed or Recurred Within Six Months After Platinum-based Chemotherapy
  • Official Title: A Prospective Phase I and II Trial of Abemaciclib + Nivolumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed or Recurred Within Six Months After Platinum-based Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 201810019
  • NCT ID: NCT03655444

Conditions

  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
AbemaciclibVerzenioPhase I: Abemaciclib + Nivolumab
NivolumabOpdivoPhase I: Abemaciclib + Nivolumab

Purpose

In phase I of the trial, the investigators aim to explore the safety and feasibility of abemaciclib in combination with nivolumab in patients with recurrent/metatstatic head and neck squamous cell carcinoma (RM-HNSCC). A dose de-escalation study design will be used to determine the recommended phase II dose (RP2D) of abemaciclib given with the standard dose of nivolumab. In phase II of the trial, the investigators aim to determine if abemaciclib and nivolumab will improve the one year survival from 36% (historical comparison with nivolumab) to 60% (abemaciclib + nivolumab) in patients with RM-HNSCC that had progressed or recurred within six months after platinum-based chemotherapy. Patients will be treated with abemaciclib at the recommended phase 2 dose (RP2D) in combination with standard doses of nivolumab. If this aim is met, genome sequencing, bulk and single cell RNAseq, and selected protein expression and deep cellular phenotyping will be performed on tumor tissue and blood obtained before and during treatment with abemaciclib and nivolumab. These biomarker data will be correlated with survival and tumor response to abemaciclib and nivolumab.

Trial Arms

NameTypeDescriptionInterventions
Phase I: Abemaciclib + NivolumabExperimental-Abemaciclib will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Abemaciclib
  • Nivolumab
Phase II: Abemaciclib + NivolumabExperimental-Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
  • Abemaciclib
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Incurable RM-HNSCC, defined as disease not amenable to cure by surgery and/or
             radiation therapy (or patient declines or is ineligible for surgery and/or radiation
             therapy).

          -  Disease Evaluation:

               -  Phase I: evaluable or measurable disease.

               -  Phase II: measurable disease, defined as lesions that can be accurately measured
                  in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT
                  scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm by clinical exam.

          -  Prior Treatment:

               -  Phase I: any number of lines of prior therapy for RM-HNSCC.

               -  Phase I: prior therapy with inhibitors of CDK4/6 or PD-L1/PD-1 is acceptable.

               -  Phase II: RM-HNSCC that progressed or recurred within six months of
                  platinum-based therapy (given for curable or incurable disease).

               -  Phase II: prior therapy with inhibitors of CDK4/6 or PD-L1/PD-1 is not
                  acceptable.

          -  18 years of age or older

          -  Performance status 0-1 (ECOG)

          -  Adequate blood and organ function as defined:

               -  Absolute neutrophil count ≥ 1,500/mcL

               -  Platelets ≥ 100,000/mcL

               -  Hemoglobin ≥ 9.0 g/dL

               -  Total bilirubin ≤ 1.5 mg/dL

               -  AST(SGOT) ≤ 5 x IULN and ALT(SGPT) ≤ 5 x IULN

               -  Creatinine ≤ 2 x ULN OR creatinine clearance ≥ 40 mL/min/1.73 m2

               -  INR ≤ 1.5 x ULN and PTT ≤ 1.5 x ULN (Patients are allowed to be on
                  anticoagulation)

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control, abstinence) beginning 14 days prior to
             first dose of abemaciclib, through the dosing period, and for at least 28 days after.

          -  Signed IRB approved written informed consent document.

        Exclusion Criteria:

          -  Phase II: prior inhibitors of CDK4/6 or PD-L1/PD-1 for treatment of incurable HNSCC.

          -  Radiation, chemotherapy, targeted or investigational therapy within 14 days of
             treatment start.

          -  History of other malignancy ≤ 1 year prior to consent with the exception of completely
             resected skin carcinoma or other cancers with a low risk of recurrence.

          -  Ongoing toxicity attributed to prior anti-cancer therapy that is > grade 1, except
             alopecia, anemia, fatigue or rash.

          -  Active central nervous system metastases: defined as currently receiving radiation
             therapy to metastatic CNS disease. Once radiation therapy is completed, patients with
             CNS disease are eligible if they meet all other criteria for enrollment.

          -  History of severe allergic reactions attributed to agents used in the study.

          -  Serious uncontrolled inter-current illness within the 3 months prior to study entry or
             psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test
             within 7 days of first dose of treatment.

          -  Active serious autoimmune disease requiring systemic immunosuppression (biologics,
             prednisone equivalent dose > 20 mg/day).

          -  Current use of strong CYP3A inhibitors or inducers.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I only: Determine the recommended phase 2 dose of abemaciclib combined with a fixed dose of nivolumab
Time Frame:Completion of enrollment to Phase I portion of study (estimated to be 3 months)
Safety Issue:
Description:-The RP2D of abemaciclib is defined as the highest dose level at which fewer than 2 patients of a cohort of three patients experience a dose-limiting toxicity (DLT) during the first cycle.

Secondary Outcome Measures

Measure:Phase II only: Best tumor response
Time Frame:Through completion of treatment (estimated to be 5 months)
Safety Issue:
Description:Complete response: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, Disappearance of all non-target lesions and normalization of tumor marker level. Partial response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
Measure:Phase II only: Duration of tumor response
Time Frame:Through completion of treatment (estimated to be 5 months)
Safety Issue:
Description:-The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Measure:Phase II only: Progression-free survival (PFS)
Time Frame:Through completion of treatment (estimated to be 5 months)
Safety Issue:
Description:-PFS is defined as the time from treatment to the date of progression or death, whichever occurs first. The alive patients without progression is censored at the last follow-up.
Measure:Phase II only: Adverse events (AEs) associated with the combination of abemaciclib and nivolumab.
Time Frame:Through 30 days after completion of treatment (estimated to be 6 months)
Safety Issue:
Description:-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Washington University School of Medicine

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