Clinical Trials /

Clinical Trial of Abemaciclib in Combination With Pembrolizumab in Patients With Metastatic or Recurrent Head and Neck Cancer

NCT03938337

Description:

To assess the objective response rate of tumor lesions to abemaciclib in combination with pembrolizumab in patients with metastatic or recurrent squamous cell carcinoma of head and neck.

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

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Clinical Trial of Abemaciclib in Combination With Pembrolizumab in Patients With Metastatic or Recurrent Head and Neck Cancer
  • Official Title: Clinical Trial of Abemaciclib in Combination With Pembrolizumab in Patients With Metastatic or Recurrent Head and Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: UAB 1891
  • NCT ID: NCT03938337

Conditions

  • Head and Neck Cancer

Interventions

DrugSynonymsArms
Cohort 1 Not Previously TreatedCDK4:CDK6Cohort 1 Not Previously Treated
Cohort 2 Treated PreviouslyCDK4:CDK6Cohort 2 Treated Previously

Purpose

To assess the objective response rate of tumor lesions to abemaciclib in combination with pembrolizumab in patients with metastatic or recurrent squamous cell carcinoma of head and neck.

Detailed Description

      Immunotherapy has been recently approved for patients with metastatic or recurrent squamous
      cell carcinoma of the head and neck. However, only a small percentage of patients experience
      long-term control, necessitating new therapeutic strategies. Recently, it was shown
      preclinically and in breast tumors that abemaciclib stimulates production of type III
      interferons and hence enhances tumor antigen presentation. Abemaciclib also suppressed the
      proliferation of regulatory T cells. These events promote cytotoxic T-cell-mediated clearance
      of tumor cells, which is further enhanced by the addition of immune checkpoint blockade.
      Based on these data, a phase II trial in patients with metastatic or recurrent head and neck
      cancer who are eligible for immunotherapy is proposed to investigate the combination of
      abemaciclib with pembrolizumab. Tumor & blood analysis for interferon gamma signature will be
      explored as possible biomarkers.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 Not Previously TreatedExperimentalPatients with metastatic or recurrent head and neck cancer who have not been treated previously with immunotherapy.
  • Cohort 1 Not Previously Treated
Cohort 2 Treated PreviouslyExperimentalPatients with metastatic or recurrent head and neck cancer who have been treated previously with immunotherapy.
  • Cohort 2 Treated Previously

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed (core biopsy proven) metastatic or recurrent squamous cell
             carcinoma of head and neck

          -  Adequate pulmonary and cardiac function

          -  Available archived tissue of primary tumor or resected tumor specimen with adequate
             samples

          -  Prior treatment with immune checkpoint inhibitor is not allowed in cohort 1 patients.
             Patients in cohort 2 should have failed or progressed on prior immune checkpoint
             inhibitor

          -  Eastern Cooperative Oncology Group Performance Status(ECOG PS) = 0 or 1

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

          -  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

          -  The patient is able to swallow oral medications

          -  Adequate hematologic and end-organ function

          -  Absolute Neutrophil Count (ANC) >= 1500/mm3

          -  Platelet count ≥ 100,000/mm3

          -  Hemoglobin (Hb) ≥ 8g/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)

          -  Creatinine (Cr) ≤ 1.5 x Upper Limit of Normal (ULN) or Creatinine Clearance (CrCl) ≥
             60 ml/min

          -  Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome, who can have total
             Bilirubin < 2.0 x ULN and direct bilirubin within normal limits are permitted.)

          -  Aspartate Aminotransferase (AST) and Alanine aminotransferase (ALT) and alkaline
             phosphatase ≤ ULN

          -  Agreement to remain abstinent or use appropriate contraception, among women of
             childbearing potential

          -  Willingness and ability to consent for self to participate in study

          -  Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and other study procedures

        Exclusion Criteria:

          -  Autoimmune disease (Note: Vitiligo, type 1 diabetes mellitus, residual hypothyroidism
             due to autoimmune thyroiditis only requiring hormone replacement, and conditions not
             expected to recur in the absence of an external trigger are permitted.)

          -  Condition requiring systemic treatment with either corticosteroids (>10 mg daily
             prednisone equivalent) or other immunosuppressive medications within 14 days prior to
             study treatment (Note: Inhaled and topical steroids, and adrenal replacement steroid
             doses > 10 mg daily prednisone equivalent, are permitted in the absence of active
             autoimmune disease.)

          -  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).

          -  Immunosuppression, of any kind

          -  Prior treatment with Cyclin-Dependent Kinase(CDK) 4/6 Inhibitor

          -  Major surgical procedure or significant traumatic injury within 4 weeks prior to study
             treatment, and must have fully recovered from any such procedure

          -  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

          -  Angina, myocardial infarction (MI), symptomatic congestive heart failure,
             cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary
             embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery
             bypass grafting (CABG) within 6 months prior to study treatment

          -  Known active viral or non-viral hepatitis or cirrhosis

          -  Any active infection requiring systemic treatment, positive tests for Hepatitis B
             surface antigen or Hepatitis C ribonucleic acid (RNA).

          -  History of gastrointestinal perforation or fistula in the 6 months prior to study
             treatment, unless underlying risk has been resolved (e.g., through surgical resection
             or repair)

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
             related illness

          -  Pregnancy or breastfeeding - Female patients must be surgically sterile (i.e., ≥6
             weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal
             ligation) or be postmenopausal, or must agree to use effective contraception during
             the study and for 4 months following last dose of treatment. All female patients of
             reproductive potential must have a negative pregnancy test (serum or urine) within 7
             days prior to study treatment. Male patients must be surgically sterile or must agree
             to use effective contraception during the study and for 4 months following last dose
             of treatment.

          -  Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or may
             interfere with the interpretation of study results and, in the judgment of the
             Investigator, would make the patient inappropriate for this study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To assess the objective response rate of tumor lesions using scans
Time Frame:Baseline
Safety Issue:
Description:Patients will be evaluated for their tumor response to treatment using RECIST criteria on their scans

Secondary Outcome Measures

Measure:Number of participants experiencing adverse events grade 3 or greater
Time Frame:Baseline to 1 month
Safety Issue:
Description:Measure adverse events grade 3 or greater to evaluate safety and tolerability
Measure:Number of participants experiencing adverse events grade 3 or greater
Time Frame:Baseline to 6 months
Safety Issue:
Description:Measure adverse events grade 3 or greater to evaluate safety and tolerability
Measure:Number of participants experiencing adverse events grade 3 or greater
Time Frame:Baseline to 12 months
Safety Issue:
Description:Measure adverse events grade 3 or greater to evaluate safety and tolerability
Measure:To assess progression free survival (PFS)
Time Frame:baseline to 6 months
Safety Issue:
Description:Using scan results to assess whether tumor has progressed and the time;
Measure:To assess progression free survival (PFS)
Time Frame:baseline to 12 months
Safety Issue:
Description:Using scan results to assess whether tumor has progressed and the time;
Measure:To assess overall survival
Time Frame:baseline to 6 months
Safety Issue:
Description:time that the patient is experiencing survival
Measure:To assess overall survival
Time Frame:baseline to 12 months
Safety Issue:
Description:time that the patient is experiencing survival
Measure:To assess the time to tumor response
Time Frame:baseline to 6 months
Safety Issue:
Description:using scan results to assess the time it takes for the tumor to respond to treatment
Measure:To assess the time to tumor response
Time Frame:baseline to 12 months
Safety Issue:
Description:using scan results to assess the time it takes for the tumor to respond to treatment
Measure:To assess the duration of response
Time Frame:baseline to 6 months
Safety Issue:
Description:using scan results to measure the total amount of time that the tumor is responding to treatment
Measure:To assess the duration of response
Time Frame:baseline to 12 months
Safety Issue:
Description:using scan results to measure the total amount of time that the tumor is responding to treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Alabama at Birmingham

Trial Keywords

  • immunotherapy
  • abemaciclib
  • pembrolizumab
  • Cyclin-Dependent Kinase (CDK): CDK4
  • Cyclin-Dependent Kinase (CDK): CDK6

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