Abemaciclib and Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer

NCT03938337 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: UAB 1891
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Head and Neck Cancer

Keywords

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

Outcome Measures

Primary Outcomes (3)

• To Assess the Objective Response Rate of Tumor Lesions Using Scans

  Patients will be evaluated for their tumor response to treatment using RECIST criteria on their scans

  Baseline

• To Assess the Objective Response Rate of Tumor Lesions Using Scans

  Patients will be evaluated for their tumor response to treatment using RECIST criteria on their scans

  Baseline to 5 months

• To Assess the Objective Response Rate of Tumor Lesions Using Scans

  Patients will be evaluated for their tumor response to treatment using RECIST criteria on their scans

  Baseline to 8 months

Secondary Outcomes (11)

• Number of Participants Experiencing Adverse Events Grade 3 or Greater

  Baseline to 1 month

• Number of Participants Experiencing Adverse Events Grade 3 or Greater

  Baseline to 6 months

• Number of Participants Experiencing Adverse Events Grade 3 or Greater

  Baseline to 12 months

• To Assess Progression Free Survival (PFS)

  baseline to 6 months

• To Assess Progression Free Survival (PFS)

  baseline to 12 months

Study Arms (2)

Cohort 1 Not Previously Treated

EXPERIMENTAL

Patients with metastatic or recurrent head and neck cancer who have not been treated previously with immunotherapy.

Drug: Cohort 1 Not Previously Treated

Cohort 2 Treated Previously

EXPERIMENTAL

Patients with metastatic or recurrent head and neck cancer who have been treated previously with immunotherapy.

Drug: Cohort 2 Treated Previously

Interventions

Cohort 1 Not Previously Treated DRUG

Abemaciclib 150mg by mouth twice daily Pembrolizumab 200mg IV every 3 weeks

Also known as: CDK4:CDK6

Cohort 1 Not Previously Treated

Cohort 2 Treated Previously DRUG

Abemaciclib 150mg by mouth twice daily Pembrolizumab 200mg IV every 3 weeks

Also known as: CDK4:CDK6

Cohort 2 Treated Previously

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Results Point of Contact

• Title: Eddy S. Yang
• Organization: O'Neal Comprehensive Cancer Center at University of Alabama at Birmingham

eyang@uab.edu

12059960780

Study Officials

• Eddy Yang, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: May 2, 2019
• First Posted: May 6, 2019
• Study Start: October 8, 2019
• Primary Completion: April 3, 2020
• Study Completion: April 3, 2020
• Last Updated: July 9, 2021
• Results First Posted: July 9, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: As long as study record is posted on CT.gov
• Access Criteria: To Be Determined

Locations

US (1)