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

NCT03655444 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 201810019
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

In phase I of the trial, the investigators aim to explore the safety and feasibility of abemaciclib in combination with nivolumab in patients with recurrent/metatstatic head and neck squamous cell carcinoma (RM-HNSCC). A dose de-escalation study design will be used to determine the recommended phase II dose (RP2D) of abemaciclib given with the standard dose of nivolumab. In phase II of the trial, the investigators aim to determine if abemaciclib and nivolumab will improve the one year survival from 36% (historical comparison with nivolumab) to 60% (abemaciclib + nivolumab) in patients with RM-HNSCC that had progressed or recurred within six months after platinum-based chemotherapy. Patients will be treated with abemaciclib at the recommended phase 2 dose (RP2D) in combination with standard doses of nivolumab. If this aim is met, genome sequencing, bulk and single cell RNAseq, and selected protein expression and deep cellular phenotyping will be performed on tumor tissue and blood obtained before and during treatment with abemaciclib and nivolumab. These biomarker data will be correlated with survival and tumor response to abemaciclib and nivolumab.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Phase I Only: Determine the Recommended Phase 2 Dose of Abemaciclib Combined With a Fixed Dose of Nivolumab

  -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.

  Completion of enrollment to Phase I portion of study (estimated to be 3 months)

• Overall Survival (OS) Rate

  * 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.

  Until death (estimated average of 13 months)

Secondary Outcomes (5)

• Phase II Only: Best Overall Tumor Response

  Through completion of treatment (estimated to be 5 months)

• Phase II Only: Duration of Tumor Response

  Through completion of treatment (estimated to be 5 months)

• Progression-free Survival (PFS)

  Through completion of treatment (estimated to be 5 months)

• Adverse Events (AEs) Associated With the Combination of Abemaciclib and Nivolumab.

  Through 30 days after completion of treatment (estimated to be 6 months)

• Phase II Lead-In Only: Changes in Peripheral Blood Lymphocyte Subsets

  Compare before and after one week of abemaciclib monotherapy

Study Arms (2)

Phase I: Abemaciclib + Nivolumab

EXPERIMENTAL

* 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.

Drug: Abemaciclib; Drug: Nivolumab

Phase II: Abemaciclib + Nivolumab

EXPERIMENTAL

* Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose (150 mg) 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 (150 mg) (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.

Drug: Abemaciclib; Drug: Nivolumab; Procedure: Tumor biopsy; Procedure: Peripheral blood; Other: EORTC QLQ-30

Interventions

Abemaciclib DRUG

Abemaciclib is an investigational agent for this trial and will be supplied by Lilly Oncology, free of charge to the patient.

Also known as: Verzenio

Phase I: Abemaciclib + Nivolumab; Phase II: Abemaciclib + Nivolumab

Nivolumab DRUG

Nivolumab is commercially available

Also known as: Opdivo

Phase I: Abemaciclib + Nivolumab; Phase II: Abemaciclib + Nivolumab

Tumor biopsy PROCEDURE

* Phase II patients only * If the patient consents, fresh tumor tissue will be collected at baseline and then during Cycle 2 (between days 8-22) of abemaciclib and nivolumab.

Phase II: Abemaciclib + Nivolumab

Peripheral blood PROCEDURE

* Phase II patients only * Peripheral blood will be collected at baseline, at the end of the Lead In (cycle 1 day 1 prior to treatment), during cycle 2 (between days 8-22), and during cycle 3 (between days 21-28). If patient does not have progression after cycle 3, patient will also have peripheral blood collected at time of progression.

Phase II: Abemaciclib + Nivolumab

EORTC QLQ-30 OTHER

* Phase II patients only * Screening , Cycle 2 D1, Cycle 4 D1, and End of treatment (EOT)

Phase II: Abemaciclib + Nivolumab

Eligibility Criteria

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

You may qualify if:

• Incurable RM-HNSCC, defined as disease not amenable to cure by surgery and/or radiation therapy (or patient declines or is ineligible for surgery and/or radiation therapy).
• Disease Evaluation:
• Phase I: evaluable or measurable disease.
• Phase II: measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm by clinical exam.
• Prior Treatment:
• Phase I: any number of lines of prior therapy for RM-HNSCC.
• Phase I: prior therapy with inhibitors of CDK4/6 or PD-L1/PD-1 is acceptable.
• Phase II: RM-HNSCC that progressed or recurred within six months of platinum-based therapy (given for curable or incurable disease).
• Phase II: prior therapy with inhibitors of CDK4/6 or PD-L1/PD-1 is not acceptable.
• years of age or older
• Performance status 0-1 (ECOG)
• Adequate blood and organ function as defined:
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 8.0 g/dL

You may not qualify if:

• Phase II: prior inhibitors of CDK4/6 or PD-L1/PD-1 for treatment of incurable HNSCC.
• Radiation within 14 days of treatment start (patients who received radiotherapy must have completed and fully recovered from the acute side effects of radiotherapy), chemotherapy, targeted or investigational therapy within 21 days of treatment start.
• History of other malignancy ≤ 1 year prior to consent with the exception of completely resected skin carcinoma or other cancers with a low risk of recurrence.
• Ongoing toxicity attributed to prior anti-cancer therapy that is \> grade 1, except alopecia or peripheral neuropathy
• Active central nervous system metastases: defined as currently receiving radiation therapy to metastatic CNS disease. Once radiation therapy is completed, patients with CNS disease are eligible if they meet all other criteria for enrollment.
• History of severe allergic reactions attributed to agents used in the study.
• Serious uncontrolled inter-current illness within the 3 months prior to study entry or psychiatric illness/social situations that would limit compliance with study requirements.
• Serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (i.e., interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], 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).
• Active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• 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.
• Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 7 days of first dose of treatment.
• Active serious autoimmune disease requiring systemic immunosuppression (biologics, prednisone equivalent dose \> 20 mg/day).
• Current use of strong CYP3A inhibitors or inducers.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

abemaciclib; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Douglas R. Adkins, M.D.
• Organization: Washington University School of Medicine

dadkins@wustl.edu

314-747-8475

Study Officials

• Douglas R Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: August 31, 2018
• Study Start: May 29, 2019
• Primary Completion: August 24, 2020
• Study Completion: August 24, 2020
• Last Updated: December 3, 2020
• Results First Posted: December 3, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)