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

NCT ID: NCT03655444

Last Updated: 2020-12-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-29
• Study Completion Date: 2020-08-24

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I: Abemaciclib + Nivolumab

• 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.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

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

Nivolumab

Intervention Type: DRUG

Nivolumab is commercially available

Phase II: Abemaciclib + Nivolumab

• 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.

Group Type: EXPERIMENTAL

Abemaciclib

Intervention Type: DRUG

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

Nivolumab

Intervention Type: DRUG

Nivolumab is commercially available

Tumor biopsy

Intervention Type: 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.

Peripheral blood

Intervention Type: 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.

EORTC QLQ-30

Intervention Type: OTHER

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

Interventions

Abemaciclib

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

Intervention Type: DRUG

Nivolumab

Nivolumab is commercially available

Intervention Type: DRUG

Tumor biopsy

• 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.

Intervention Type: PROCEDURE

Peripheral blood

• 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.

Intervention Type: PROCEDURE

EORTC QLQ-30

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

Intervention Type: OTHER

Other Intervention Names

Verzenio; Opdivo

Eligibility Criteria

Inclusion Criteria

• 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.
• 18 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
• Total bilirubin ≤ 1.5 x ULN mg/dL
• AST(SGOT) ≤ 3 x IULN and ALT(SGPT) ≤ 3 x IULN
• Creatinine ≤ 2 x ULN OR creatinine clearance ≥ 40 mL/min/1.73 m2
• INR ≤ 1.5 x ULN and PTT ≤ 1.5 x ULN (Patients are allowed to be on anticoagulation)
• Able to swallow oral medication
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) beginning 14 days prior to first dose of abemaciclib, through the dosing period, and for at least 28 days after.
• Signed IRB approved written informed consent document.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Douglas R Adkins, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.siteman.wustl.edu

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

Other Identifiers

201810019

Identifier Type: -

Identifier Source: org_study_id