A Phase II Study of ACR-368 and Low Dose Gemcitabine in R/M HNSCC

Trial Title: A Phase II Study of ACR-368 and Low Dose Gemcitabine in R/M HNSCC

NCT ID: NCT06597565

Condition: Head and Neck Squamous Cell Carcinoma

Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Gemcitabine
Prexasertib

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Gemcitabine
Description: Gemcitabine is a standard of care given at ultralow dose in combination with the experimental drug ACR-368.
Arm group label: Cohort A (p16/HPV-neg)
Arm group label: Cohort B (p16/HPV-pos)

Intervention type: Drug
Intervention name: ACR-368
Description: ACR-368 is an experimental drug.
Arm group label: Cohort A (p16/HPV-neg)
Arm group label: Cohort B (p16/HPV-pos)

Other name: Prexasertib

Summary: The purpose of the study is to determine the activity and safety of ACR-368 (prexasertib) in combination with gemcitabine in participants with Head and Neck Squamous Cell Carcinoma (HNSCC). Participants will receive the study drugs ACR-368 and a low dose of gemcitabine once every 2 weeks in 4-week cycles and will continue on treatment unless the disease deteriorates.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Patient (or a legally authorized representative) must understand and voluntarily sign informed consent prior to any study-related assessments/procedures being conducted. - Must be able and willing to comply with the study visit schedule and protocol requirements. - Must have sufficient archived tumor tissue available for p16 immunohistochemistry (IHC) staining if the status is unknown. HPV status determined by HPV DNA sequencing, HPV DNA/RNA in situ hybridization, or equivalent assays using tumor tissue or cell free HPV DNA testing or equivalent using blood-based assays are also acceptable. If there is a discrepancy between p16 IHC and HPV detection assay results, HPV detection assay result will be used. - Must have sufficient archived tumor tissue available for OncoSignature determination. The tumor tissue must be less than 3 months old from the enrollment date. There should not be any intervening systemic therapy from the date of tumor tissue collection. If not, patient must agree to a fresh tumor biopsy before starting the treatments. - Must agree to a biopsy after the lead-in LDG infusion and at the time of disease progression (or end of treatment if applicable). - Must have R/M HNSCC including oral cavity, oropharynx, larynx, and hypopharynx. Patients with p16-positive or HPV-positive unknown primary of head and neck are eligible. - Must have been treated with one prior line of PD-1/PD-L1 inhibitor with/without chemotherapy. Patients who are immunotherapy ineligible due to history of autoimmune disease or steroid requirement (prednisone >10mg per day or equivalent) are allowed to enroll without the one prior line of PD-1/PD-L1 inhibitor with/without chemotherapy. There is no limitation on the number of prior therapies received in the R/M setting. - Must have at least one measurable lesion as defined by RECIST v1.1. - Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. - Must meet the laboratory criteria outlined in the protocol. Blood transfusion and/or blood product support are allowed. - Patients of childbearing potential and patients whose sexual partners are of childbearing potential must be willing to practice an approved method of highly effective birth control with their partners starting at the time of informed consent and for 1 year after the completion of the study treatment regimen. Exclusion Criteria: - Patients should not have any prior systemic therapy for 4 weeks from the time of the study treatment. - Patients should not have any palliative radiation therapy for 2 weeks from the time of the study treatment. Palliative radiation therapy is permitted during the study treatment if it does not involve target lesions. - Patients with prior therapy-related toxicities Grade >1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0; except for dysphagia, alopecia, or vitiligo. Immunotherapy-related endocrinopathies stable for at least 1 month, and controlled with hormonal replacement, are not excluded. Grade 2 neuropathy stable for at least 2 weeks and controlled with supportive care medications are not excluded. - Patients with symptomatic and/or untreated brain metastases (of any size and any number). Patients with definitively treated brain metastases may be eligible, must be stable for at least 2 weeks and must be asymptomatic with or without prednisone <10mg (or equivalent). - Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association (NYHA) Class 2 or higher. - Patients with cardiovascular disease defined as: A) Uncontrolled hypertension defined as blood pressure > 160/90 mmHg at Screening confirmed by repeat (medication permitted). B) History of torsades de pointes, significant Screening electrocardiogram (ECG) abnormalities, including ventricular rhythm disturbances, unstable cardiac arrhythmia requiring medication, pathologic symptomatic bradycardia, left bundle branch block, second degree atrioventricular (AV) block type II, third degree AV block, Grade ≥ 2 bradycardia, uncorrected hypokalemia not amenable to correction, congenital long QT syndrome, prolonged QT interval due to medications, corrected QT (QTc) > 450 msec (for men) or > 470 msec (for women). C) Symptomatic heart failure (per New York Heart Association guidelines; (Caraballo, 2019), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction < 20%, transient ischemic attack, or cerebrovascular accident within 6 months of Day 1). - Patients who have had another primary malignancy within the previous 3 years (except for those who do not require treatment or have been curatively treated >1 year ago, and in the judgment of the Investigator, do not pose a significant risk of recurrence; including, but not limited to, non-melanoma skin cancer, ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS], or prostate cancer Gleason score ≤6.). - Patients who are of the following protected classes will be excluded: Pregnant, parturient, or breastfeeding women. Persons who are hospitalized without consent or those deprived of liberty because of a judiciary or administrative decision. Patients with a legal protection measure or a person who cannot express his/her consent and for whom a legally authorized representative is not available. - Patients in emergency situations who cannot consent to the study and for whom a legally authorized representative is not available.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Moffitt Cancer Center

Address:
City: Tampa
Zip: 33612
Country: United States

Status: Recruiting

Contact:
Last name: Kara Hoffman

Phone: 813-745-6020
Email: kara.hoffman@moffitt.org

Investigator:
Last name: Christine Chung, MD
Email: Principal Investigator

Investigator:
Last name: Kedar Kirtane, MD
Email: Sub-Investigator

Investigator:
Last name: Julie Kish, MD
Email: Sub-Investigator

Investigator:
Last name: Guilherme Rabinowits, MD
Email: Sub-Investigator

Start date: September 25, 2024

Completion date: August 23, 2028

Lead sponsor:
Agency: H. Lee Moffitt Cancer Center and Research Institute
Agency class: Other

Collaborator:
Agency: Acrivon Therapeutics
Agency class: Industry

Source: H. Lee Moffitt Cancer Center and Research Institute

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06597565