- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03938337
Abemaciclib and Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer
June 16, 2021 updated by: Eddy Yang, University of Alabama at Birmingham
Clinical Trial of Abemaciclib in Combination With Pembrolizumab in Patients With Metastatic or Recurrent Head and Neck Cancer
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama at Birmingham
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1 Not Previously Treated
Patients with metastatic or recurrent head and neck cancer who have not been treated previously with immunotherapy.
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Abemaciclib 150mg by mouth twice daily Pembrolizumab 200mg IV every 3 weeks
Other Names:
|
Experimental: Cohort 2 Treated Previously
Patients with metastatic or recurrent head and neck cancer who have been treated previously with immunotherapy.
|
Abemaciclib 150mg by mouth twice daily Pembrolizumab 200mg IV every 3 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To Assess the Objective Response Rate of Tumor Lesions Using Scans
Time Frame: Baseline
|
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
Time Frame: Baseline to 5 months
|
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
Time Frame: Baseline to 8 months
|
Patients will be evaluated for their tumor response to treatment using RECIST criteria on their scans
|
Baseline to 8 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Experiencing Adverse Events Grade 3 or Greater
Time Frame: Baseline to 1 month
|
Measure adverse events grade 3 or greater to evaluate safety and tolerability
|
Baseline to 1 month
|
Number of Participants Experiencing Adverse Events Grade 3 or Greater
Time Frame: Baseline to 6 months
|
Measure adverse events grade 3 or greater to evaluate safety and tolerability
|
Baseline to 6 months
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Number of Participants Experiencing Adverse Events Grade 3 or Greater
Time Frame: Baseline to 12 months
|
Measure adverse events grade 3 or greater to evaluate safety and tolerability
|
Baseline to 12 months
|
To Assess Progression Free Survival (PFS)
Time Frame: baseline to 6 months
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Using scan results to assess whether tumor has progressed and the time;
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baseline to 6 months
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To Assess Progression Free Survival (PFS)
Time Frame: baseline to 12 months
|
Using scan results to assess whether tumor has progressed and the time;
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baseline to 12 months
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To Assess Overall Survival
Time Frame: baseline to 6 months
|
time that the patient is experiencing survival
|
baseline to 6 months
|
To Assess Overall Survival
Time Frame: baseline to 12 months
|
time that the patient is experiencing survival
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baseline to 12 months
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To Assess the Time to Tumor Response
Time Frame: baseline to 6 months
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using scan results to assess the time it takes for the tumor to respond to treatment
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baseline to 6 months
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To Assess the Time to Tumor Response
Time Frame: baseline to 12 months
|
using scan results to assess the time it takes for the tumor to respond to treatment
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baseline to 12 months
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To Assess the Duration of Response
Time Frame: baseline to 6 months
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using scan results to measure the total amount of time that the tumor is responding to treatment
|
baseline to 6 months
|
To Assess the Duration of Response
Time Frame: baseline to 12 months
|
using scan results to measure the total amount of time that the tumor is responding to treatment
|
baseline to 12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Eddy Yang, MD, University of Alabama at Birmingham
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 8, 2019
Primary Completion (Actual)
April 3, 2020
Study Completion (Actual)
April 3, 2020
Study Registration Dates
First Submitted
May 2, 2019
First Submitted That Met QC Criteria
May 3, 2019
First Posted (Actual)
May 6, 2019
Study Record Updates
Last Update Posted (Actual)
July 9, 2021
Last Update Submitted That Met QC Criteria
June 16, 2021
Last Verified
June 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UAB 1891
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
To Be Determined
IPD Sharing Time Frame
As long as study record is posted on CT.gov
IPD Sharing Access Criteria
To Be Determined
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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