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A Biomarker-driven, Open Label, Single Arm, Multicentre Phase II Study of Abemaciclib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Who Failed to Platinum-based Therapy

NCT03356587

Description:

Open, multicenter, single arm, phase II, biomarker driven umbrella trial for head and neck squamous cell carcinoma (FGFR inhibitor, CDK4/6 inhibitor, pan HER inhibitor, PI3K inhibitor, PD1/PD-L1 inhibitor)

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Biomarker-driven, Open Label, Single Arm, Multicentre Phase II Study of Abemaciclib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Who Failed to Platinum-based Therapy
  • Official Title: A Biomarker-driven, Open Label, Single Arm, Multicentre Phase II Study of Abemaciclib in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Who Failed to Platinum-based Therapy

Clinical Trial IDs

  • ORG STUDY ID: 13Y-MC-E011
  • NCT ID: NCT03356587

Conditions

  • HNSCC
  • Head and Neck Neoplasms

Interventions

DrugSynonymsArms
AbemaciclibArm4: Abemaciclib

Purpose

Open, multicenter, single arm, phase II, biomarker driven umbrella trial for head and neck squamous cell carcinoma (FGFR inhibitor, CDK4/6 inhibitor, pan HER inhibitor, PI3K inhibitor, PD1/PD-L1 inhibitor)

Detailed Description

      This study will be conducted as a treatment arm 4 of the umbrella clinical
      trial.(NCT03292250)

      During or after palliative 1st line platinum based chemotherapy, we will perform prescreening
      NGS based molecular characterization. The molecular characterization will be done by
      following three methods.

        -  NGS : Agilent SureSelect Target Enrichment (245 genes)

        -  Nanostring nCounter including immune signature

        -  IHC : PD-L1

      The present trial will investigate the efficacy and safety of abemaciclib in patients with
      recurrent or metastatic HPV (-) HNSCC with genetic alterations of cell cycle pathway who
      failed to platinum-based therapy. We will also evaluate feasibility and the effect on
      decision making of next generation sequencing of HNSCC.
    

Trial Arms

NameTypeDescriptionInterventions
Arm4: AbemaciclibExperimentalAbemaciclib represents a selective and potent small molecule CDK4 and CDK6 dual inhibitor with broad antitumor activity in preclinical pharmacology models.(oral class) Patients will be instructed to take Abemaciclib orally at a dose of 200mg bid with a glass of water twice daily, in a fasting state or with a light fat-free meal, and as close as possible to the same time each day
  • Abemaciclib

Eligibility Criteria

        Inclusion Criteria:

          -  (1) Histologically or cytologically confirmed recurrent or metastatic HNSCC, except
             nasopharyngeal carcinoma (2) Age ≥20 (3) ECOG performance status of 0-1 (4)
             Ineligibility for local therapy (surgery or radiotherapy) (5) Prior palliative
             chemotherapy including platinum-based chemotherapy. When recurred within 6 months of
             definitive/neoadjuvant/adjuvant chemo- or chemoradiation, the chemotherapy is
             considered a line of palliative chemotherapy (6) At least one measurable lesion by
             RECIST ver 1.1 (7) p16 negative and intact Rb and genetic alterations in CDK4/6
             pathway (8) Adequate organ function for all of the following criteria, as defined
             below.

          -  Absolute neutrophil count (ANC) ≥1500 cells/mm3

          -  Platelets ≥100,000 cells/mm3

          -  Hemoglobin ≥ 8 g/dL (Patients may receive erythrocyte transfusions to achieve this
             hemoglobin level at the discretion of the investigator. Initial treatment must not
             begin earlier than the day after the erythrocyte transfusion.)

          -  Serum creatinine ≤1.5 x institution upper limit of normal

          -  Total Bilirubin ≤1.5 x upper limit of normal (ULN) (Patients with Gilbert's syndrome
             with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are
             permitted.)

          -  AST (SGOT) ≤3.0 x ULN

          -  ALT (SGPT) ≤3.0 x ULN (9) If a female of childbearing potential, must have a negative
             serum pregnancy test within 7 days of the first dose of abemaciclib and agree to use a
             medically approved contraceptive method during the treatment period and for 3 months
             following the last dose of abemaciclib.

        If a male, must agree to use a reliable method of birth control and to not donate sperm
        during the study and for at least 3 months following the last dose of abemaciclib.
        Contraceptive methods may include an intrauterine device [IUD] or barrier method. If
        condoms are used as a barrier method, a spermicidal agent should be added as a double
        barrier protection.

        (10) Patients who received chemotherapy must have recovered (Common Terminology Criteria
        for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for
        residual alopecia or Grade 2 peripheral neuropathy prior to screening. A washout period of
        at least 21 days is required between last chemotherapy dose and screening (provided the
        patient did not receive radiotherapy).

        (11) Patients who received adjuvant radiotherapy must have completed and fully recovered
        from the acute effects of radiotherapy. A washout period of at least 14 days is required
        between end of radiotherapy and randomization.

        (12) The patient has provided signed informed consent and has a compliance to follow the
        study protocol.

        (13) The patient is able to swallow oral medications.

        Exclusion Criteria:

          -  (1) Prior treatment with CDK4/6 pathway inhibitors (2) Nasopharyngeal carcinoma (3)
             The patient has serious preexisting medical condition(s) that would preclude
             participation in this study (for example, interstitial lung disease, severe dyspnea at
             rest or requiring oxygen therapy, history of major surgical resection involving the
             stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a
             preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).

             (4) Pregnant woman, Breast-feeding woman (5) Recent significant bleeding history
             within 6 major vessel invasion of tumor (6) Other severe acute or chronic medical
             condition or laboratory abnormality that may increase the risk associated with trial
             participation or investigational product administration or may interfere with the
             interpretation of trial results and, in the judgment of the investigator, would make
             the patient inappropriate for entry into this trial (infection/inflammation,
             intestinal obstruction, social/psychological complications).

             (7) Patient who have an active systemic fungal and/or known viral infection (for
             example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or
             hepatitis C antibodies) (8) The patient has a personal history of any of the following
             conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological
             origin (including, but not limited to, ventricular tachycardia and ventricular
             fibrillation), or sudden cardiac arrest.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate (RR)
Time Frame:24 months
Safety Issue:
Description:RECIST version 1.1

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:24 months
Safety Issue:
Description:RECIST version 1.1
Measure:Overall survival (OS)
Time Frame:24 months
Safety Issue:
Description:Overall Survival is defined as the time from first dose to death due to any cause. Through the follow-up within 30 days after study completion or termination of the last subject, death and date of death will be checked for subject alive during treatment period
Measure:Duration of response
Time Frame:24 months
Safety Issue:
Description:RECIST version 1.1
Measure:Toxicity
Time Frame:24 months
Safety Issue:
Description:number of patients with treatment-related AE as assessed by NCI CTCAE version 4.03

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seoul National University Hospital

Trial Keywords

  • NGS
  • Nanostring
  • Biomarker Driven Umbrella Trial
  • abemaciclib

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