Immune Modulation by Abemaciclib in Head and Neck Squamous Cell Carcinoma (HNSCC). (AIM Trial)

NCT04169074 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 1906702171
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase II single-arm window trial to assess the clinical and biological effects of neoadjuvant abemaciclib in patients with HPV-negative head and neck squamous cell carcinoma (HNSCC).

Conditions

HNSCC

Keywords

Head and Neck Cancer; HNSCC; Squamous Cell Cancer; abemaciclib

Outcome Measures

Primary Outcomes (1)

• Measure quantitative change in tumor size to assess the clinical activity of abemaciclib.

  To evaluate the clinical activity of abemaciclib in patients with operable, HPV-negative HNSCC as measured by quantitative change in tumor size (∆T)1 following 10-21 (+7) days of neoadjuvant exposure. This will be measured using established RECIST v1.1 metrics for index lesions. Index lesions will be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumor (RECIST) Committee 71.

  Two months

Secondary Outcomes (1)

• Describe the safety and tolerability of neoadjuvant exposure to abemaciclib in accordance with NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5.

  Two months

Other Outcomes (10)

• Measure Interferon gamma (IFN-ɣ) gene expression signature in baseline and post-treatment tumor biopsies.

  Two months

• Measure tumor-intrinsic genetic biomarkers utilizing tumor specimen.

  Two months

• Measure the distribution of tumor-infiltrating immune cell subtypes and their activation status, as measured by nanostring.

  Two months

Study Arms (1)

Treatment with abemaciclib

EXPERIMENTAL

Treatment will consist of a single neoadjuvant cycle of 10-21 days (+7 days if needed due to surgical delay). Abemaciclib will be administered from days 1-21. Abemaciclib may be continued for an additional 7 days, or up to 28 days, for delays in planned surgery. Abemaciclib 200 mg PO twice daily on Days 1-21 (+7 days).

Drug: Abemaciclib

Interventions

Abemaciclib DRUG

Treatment will consist of a single neoadjuvant cycle of 10-21 days (+7 days). Abemaciclib will be administered from days 1-21. Abemaciclib may be continued for an additional 7 days, or up to 28 days, for delays in planned surgery.

Treatment with abemaciclib

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Cytologic or histologic diagnosis of squamous cell carcinoma of the oral cavity, p16-negative oropharynx, hypopharynx, or larynx.
• Tumors must be HPV-negative. For eligibility, tumors of the oral cavity, hypopharynx, or larynx will be considered HPV-negative without specialized testing. Tumors of the oropharynx must be HPV-negative as determined by p16 immunohistochemistry and/or HPV-DNA per local standard.
• Clinical stage I-IVa based upon the American Joint Committee on Cancer (AJCC) staging manual, 8th edition.
• Appropriate and planned for oncologic resection of the primary tumor and/or neck dissection.
• Clinically or radiologically measurable disease; the primary tumor and/or cervical nodes may be measurable according to RECIST 1.1 (tumor diameter ≥ 1 cm; short-axis lymph node diameter ≥ 1.5 cm) OR by caliper/ruler measurement (tumor diameter ≥ 1 cm).
• No prior treatment for the index (study-qualifying) HNSCC.
• Patients with two simultaneous primary tumors or bilateral tumors are included.
• The index HNSCC may be a second primary HNSCC, provided the following criteria are met:
• a. The previously treated HNSCC was treated with curative intent. b. The index HNSCC is at least 1 cm from the previously treated HNSCC. c. At least 2 years have elapsed since curative treatment of the previous HNSCC without evidence for recurrence.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1. (See Appendix 1.)
• Adequate hematologic function, as defined by:
• a. Absolute neutrophil count (ANC) ≥ 1,500/µl b. Platelets ≥ 100,000/µl c. Hemoglobin ≥ 8 g/dL
• Adequate liver function, as defined by:
• a. Bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). Patients with Gilbert's syndrome with a total bilirubin ≤ 2.0 x ULN and direct bilirubin within normal limits are permitted.
• b. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN

You may not qualify if:

• Prior treatment with any cyclin-dependent kinase (CDK) 4/6 inhibitor or anti-programmed death (PD)-1/L1 inhibitor is not allowed.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned protocol treatment. The following are exceptions to this criterion unless otherwise indicated:
• Intranasal, inhaled, or topical steroids, or local steroid injections (eg, intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (eg, CT premedication) and/or as anti-emetics
• Active or previously documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis, Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study PI
• Patients with celiac disease controlled by diet alone
• Patient has a personal history of any of the following cardiac or pulmonary abnormalities:
• Syncope of cardiovascular etiology
• Ventricular arrhythmia of pathologic origin (including, but limited to, ventricular tachycardia and ventricular fibrillation)
• Sudden cardiac arrest
• Documented history of New York Heart Association functional classification III-IV congestive heart failure

Sponsors & Collaborators

• University of Arizona: lead
• George Washington University: collaborator

Study Sites (2)

University of Arizona

Tucson, Arizona, 85719, United States

Location

George Washington Cancer Center

Washington D.C., District of Columbia, 20037, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Neoplasms, Squamous Cell

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

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

Study Officials

• Ricklie Julian, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open label Phase II single-arm window trial.

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: November 19, 2019
• Study Start: June 16, 2021
• Primary Completion: December 16, 2024
• Study Completion: January 13, 2025
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (2)