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

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ClinicalTrials.gov Identifier: NCT03655444
Recruitment Status : Terminated (Provider of drug decided to discontinue study.)
First Posted : August 31, 2018
Results First Posted : December 3, 2020
Last Update Posted : December 3, 2020
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Head and Neck Squamous Cell Carcinoma
Interventions Drug: Abemaciclib
Drug: Nivolumab
Procedure: Tumor biopsy
Procedure: Peripheral blood
Other: EORTC QLQ-30
Enrollment 6
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase I: Abemaciclib + Nivolumab Phase II: Abemaciclib + Nivolumab
Hide Arm/Group Description
  • Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
  • Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0.
  • Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Period Title: Overall Study
Started 3 3
Completed 3 3
Not Completed 0 0
Arm/Group Title Phase I: Abemaciclib + Nivolumab Phase II: Abemaciclib + Nivolumab Total
Hide Arm/Group Description
  • Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
  • Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0.
  • Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Total of all reporting groups
Overall Number of Baseline Participants 3 3 6
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 6 participants
62
(46 to 76)
62
(60 to 63)
62
(46 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 6 participants
Female
1
  33.3%
0
   0.0%
1
  16.7%
Male
2
  66.7%
3
 100.0%
5
  83.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 6 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
3
 100.0%
3
 100.0%
6
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 6 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  66.7%
2
  66.7%
4
  66.7%
White
1
  33.3%
1
  33.3%
2
  33.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 3 participants 6 participants
3 3 6
1.Primary Outcome
Title Phase I Only: Determine the Recommended Phase 2 Dose of Abemaciclib Combined With a Fixed Dose of Nivolumab
Hide 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.
Time Frame Completion of enrollment to Phase I portion of study (estimated to be 3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Only phase I participants were evaluable for this outcome measure.
Arm/Group Title Phase I: Abemaciclib + Nivolumab Phase II: Abemaciclib + Nivolumab
Hide Arm/Group Description:
  • Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
  • Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0.
  • Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Overall Number of Participants Analyzed 3 0
Measure Type: Number
Unit of Measure: mg twice per day
150
2.Primary Outcome
Title Overall Survival (OS) Rate
Hide Description
  • OS is defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise.
  • The mean survival time and standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
Time Frame Until death (estimated average of 13 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I and Phase II: Abemaciclib + Nivolumab
Hide Arm/Group Description:
  • Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
Overall Number of Participants Analyzed 6
Mean (Standard Error)
Unit of Measure: months
3.689  (0.7281)
3.Secondary Outcome
Title Phase II Only: Best Overall Tumor Response
Hide 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.
Time Frame Through completion of treatment (estimated to be 5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
-Phase II patients are the only patients evaluable.
Arm/Group Title Phase I: Abemaciclib + Nivolumab Phase II: Abemaciclib + Nivolumab
Hide Arm/Group Description:
  • Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
  • Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0.
  • Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Overall Number of Participants Analyzed 0 3
Measure Type: Count of Participants
Unit of Measure: Participants
1
  33.3%
4.Secondary Outcome
Title Phase II Only: Duration of Tumor Response
Hide 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).
Time Frame Through completion of treatment (estimated to be 5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Data was not collected for this outcome measure.
Arm/Group Title Phase I: Abemaciclib + Nivolumab Phase II: Abemaciclib + Nivolumab
Hide Arm/Group Description:
  • Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
  • Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0.
  • Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Progression-free Survival (PFS)
Hide 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.
Time Frame Through completion of treatment (estimated to be 5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I and Phase II: Abemaciclib + Nivolumab
Hide Arm/Group Description:
  • Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
Overall Number of Participants Analyzed 6
Mean (Standard Error)
Unit of Measure: months
2.82258  (0.64434)
6.Secondary Outcome
Title Adverse Events (AEs) Associated With the Combination of Abemaciclib and Nivolumab.
Hide 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.
Time Frame Through 30 days after completion of treatment (estimated to be 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I and Phase II: Abemaciclib + Nivolumab
Hide Arm/Group Description:
  • Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia
5
  83.3%
Hyperthyroidism
1
  16.7%
Hypothyroidism
1
  16.7%
Constipation
2
  33.3%
Diarrhea
3
  50.0%
Dry mouth
1
  16.7%
Dysphagia
3
  50.0%
Mucositis oral
1
  16.7%
Nausea
4
  66.7%
Vomiting
3
  50.0%
Chills
1
  16.7%
Edema face
1
  16.7%
Fatigue
5
  83.3%
Non-cardiac chest pain
1
  16.7%
Lung infection
2
  33.3%
Thrush
2
  33.3%
Vaginal infection
1
  16.7%
Alanine aminotransferase increased
1
  16.7%
Alkaline phosphatase increased
2
  33.3%
Aspartate aminotransferase increased
3
  50.0%
Blood bilirubin increased
1
  16.7%
Cholesterol high
1
  16.7%
Creatinine increased
6
 100.0%
Blood bicarbonate decreased
1
  16.7%
Lymphocyte count decreased
6
 100.0%
Neutrophil count decreased
2
  33.3%
Platelet count decreased
2
  33.3%
Weight loss
4
  66.7%
White blood cell decreased
2
  33.3%
Anorexia
3
  50.0%
Dehydration
1
  16.7%
Hypercalcemia
2
  33.3%
Hyperglycemia
4
  66.7%
Hyperkalemia
2
  33.3%
Hypoalbuminemia
3
  50.0%
Hypocalcemia
1
  16.7%
Hypoglycemia
1
  16.7%
Hypokalemia
2
  33.3%
Hypomagnesemia
1
  16.7%
Hyponatremia
3
  50.0%
Generalized muscle weakness
1
  16.7%
Arthritis
1
  16.7%
Chest wall pain
1
  16.7%
Dizziness
2
  33.3%
Dysarthria
2
  33.3%
Headache
1
  16.7%
Confusion
1
  16.7%
Depression
1
  16.7%
Acute kidney injury
1
  16.7%
Hematuria
1
  16.7%
Aspiration
2
  33.3%
Cough
4
  66.7%
Nasal congestion
1
  16.7%
Respiratory failure
1
  16.7%
Sore throat
1
  16.7%
Pruritus
2
  33.3%
Hypertension
3
  50.0%
Thromboembolic event
1
  16.7%
7.Secondary Outcome
Title Phase II Lead-In Only: Changes in Peripheral Blood Lymphocyte Subsets
Hide Description [Not Specified]
Time Frame Compare before and after one week of abemaciclib monotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
The data was not collected for this outcome measure.
Arm/Group Title Phase I: Abemaciclib + Nivolumab Phase II: Abemaciclib + Nivolumab
Hide Arm/Group Description:
  • Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
  • Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0.
  • Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse events were collected from start of treatment until 28 days after completion of treatment (median follow-up was 2.8 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase I and Phase II: Abemaciclib + Nivolumab
Hide Arm/Group Description
  • Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle
  • Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
All-Cause Mortality
Phase I and Phase II: Abemaciclib + Nivolumab
Affected / at Risk (%)
Total   3/6 (50.00%) 
Hide Serious Adverse Events
Phase I and Phase II: Abemaciclib + Nivolumab
Affected / at Risk (%)
Total   3/6 (50.00%) 
Gastrointestinal disorders   
Dysphagia  1  1/6 (16.67%) 
General disorders   
Non cardiac chest pain  1  1/6 (16.67%) 
Infections and infestations   
Lung infection  1  2/6 (33.33%) 
Investigations   
Aspartate aminotransferase increased  1  1/6 (16.67%) 
Renal and urinary disorders   
Acute kidney injury  1  1/6 (16.67%) 
1
Term from vocabulary, CTCAE (Unspecified)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase I and Phase II: Abemaciclib + Nivolumab
Affected / at Risk (%)
Total   6/6 (100.00%) 
Blood and lymphatic system disorders   
Anemia  1  5/6 (83.33%) 
Endocrine disorders   
Hyperthyroidism  1  1/6 (16.67%) 
Hypothyroidism  1  1/6 (16.67%) 
Gastrointestinal disorders   
Constipation  1  2/6 (33.33%) 
Diarrhea  1  3/6 (50.00%) 
Dry mouth  1  1/6 (16.67%) 
Dysphagia  1  2/6 (33.33%) 
Mucositis oral  1  1/6 (16.67%) 
Nausea  1  4/6 (66.67%) 
Vomiting  1  3/6 (50.00%) 
General disorders   
Chills  1  1/6 (16.67%) 
Edema face  1  1/6 (16.67%) 
Fatigue  1  5/6 (83.33%) 
Infections and infestations   
Thrush  1  2/6 (33.33%) 
Vaginal infection  1  2/6 (33.33%) 
Investigations   
Alanine aminotransferase increased  1  1/6 (16.67%) 
Alkaline phosphatase increased  1  2/6 (33.33%) 
Aspartate aminotransferase increased  1  2/6 (33.33%) 
Blood bilirubin increased  1  1/6 (16.67%) 
Cholesterol high  1  1/6 (16.67%) 
Creatinine increased  1  6/6 (100.00%) 
Blood bicarbonate decreased  1  1/6 (16.67%) 
Lymphocyte count decreased  1  6/6 (100.00%) 
Neutrophil count decreased  1  2/6 (33.33%) 
Platelet count decreased  1  2/6 (33.33%) 
Weight loss  1  4/6 (66.67%) 
White blood cell decreased  1  2/6 (33.33%) 
Hypercalcemia  1  2/6 (33.33%) 
Metabolism and nutrition disorders   
Anorexia  1  3/6 (50.00%) 
Dehydration  1  1/6 (16.67%) 
Hyperglycemia  1  4/6 (66.67%) 
Hyperkalemia  1  2/6 (33.33%) 
Hypoalbuminemia  1  3/6 (50.00%) 
Hypocalcemia  1  1/6 (16.67%) 
Hypoglycemia  1  1/6 (16.67%) 
Hypokalemia  1  2/6 (33.33%) 
Hypomagnesemia  1  1/6 (16.67%) 
Hyponatremia  1  3/6 (50.00%) 
Generalized muscle weakness  1  1/6 (16.67%) 
Musculoskeletal and connective tissue disorders   
Arthritis  1  1/6 (16.67%) 
Chest wall pain  1  1/6 (16.67%) 
Nervous system disorders   
Dizziness  1  2/6 (33.33%) 
Dysarthria  1  2/6 (33.33%) 
Headache  1  1/6 (16.67%) 
Psychiatric disorders   
Confusion  1  1/6 (16.67%) 
Depression  1  1/6 (16.67%) 
Renal and urinary disorders   
Hematuria  1  1/6 (16.67%) 
Respiratory, thoracic and mediastinal disorders   
Aspiration  1  2/6 (33.33%) 
Cough  1  4/6 (66.67%) 
Nasal congestion  1  1/6 (16.67%) 
Respiratory failure  1  1/6 (16.67%) 
Sore throat  1  1/6 (16.67%) 
Skin and subcutaneous tissue disorders   
Pruritus  1  2/6 (33.33%) 
Vascular disorders   
Hypertension  1  3/6 (50.00%) 
Thromboembolic event  1  1/6 (16.67%) 
1
Term from vocabulary, CTCAE (Unspecified)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Douglas R. Adkins, M.D.
Organization: Washington University School of Medicine
Phone: 314-747-8475
EMail: dadkins@wustl.edu
Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03655444    
Other Study ID Numbers: 201810019
First Submitted: August 30, 2018
First Posted: August 31, 2018
Results First Submitted: November 9, 2020
Results First Posted: December 3, 2020
Last Update Posted: December 3, 2020