Clinical trial NCT05816785: Pilot Study of Imatinib Cetuximab Combo for H & N Cancer
Official title: A Pilot Window of Opportunity Study of Imatinib in Combination With Cetuximab in Patients With Squamous Cell Carcinomas of the Head and Neck
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Head and Neck Cancer
Squamous Cell Carcinoma of Head and Neck
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2023-04-18
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to find if levels of a protein called AXL in tumor cells relate to how tumors respond to cetuximab (CTX) combined with imatinib in participants with head and neck cancer. This interventional study will occur in the time between diagnosis of your cancer and surgery to remove your tumor or radiation or chemoradiation treatment of your primary cancer.

Participants will undergo a research blood draw and a research biopsy as part of the screening process, and will be in this research study for approximately 13 to 16 months.

Detailed description: This is a 'window of opportunity' pilot study of oral imatinib (400 mg per day) plus cetuximab (CTX) (400mg/m2 loading dose \[dose 1\] and 250mg/m2 \[dose 2\]) for patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive surgery or radiation for treatment of their cancer. The primary objective is to determine the proportion of patients with a response to imatinib plus CTX in pre-treatment and post-treatment samples obtained as part of a window of opportunity clinical study in head and neck cancer (HNC) patients.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years at the time of consent.
* Histological confirmation of squamous cell carcinoma of the head and neck.

  * For those patients with oropharyngeal cancer, subjects must have either
  * HPV-negative status by p16 expression or HPV-DNA Expression.
  * HPV-positive status by p16 expression AND a \>10 pack year smoking history.
* Subjects must be appropriate candidates for definitive curative intent treatment, either via surgical resection, definitive radiation therapy alone, or definitive concurrent chemoradiation therapy.
* For the screening research biopsy, subjects must have sufficient tumor volume (approximately 10 cc) to accommodate at minimum 2-3 core samples for the research biopsy.
* For the post-treatment (CTX/Imatinib) research biopsy, subjects who are scheduled to receive definitive radiation therapy (+/- concurrent chemotherapy) are required to have sufficient tumor volume to accommodate at minimum 2-3 core samples for the research biopsy.
* Demonstrate adequate organ function; all screening labs to be obtained within 28 days prior to registration.

Exclusion Criteria:

* Subjects with a diagnosis of nasopharyngeal carcinoma, advanced cutaneous squamous cell carcinoma of the head and neck, or salivary gland tumors are excluded from this study.
* Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol.
* Prior chemotherapy, radiotherapy, or major surgery within 8 weeks of study enrollment or those who have not recovered (to grade ≤ 1 or baseline) from clinically significant adverse events due to agents administered more than 8 weeks earlier (alopecia and fatigue excluded). Clinical significance to be determined by the study investigator.
* Subjects who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
* Subjects who are receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to imatinib or CTX.

Primary outcomes:
measure: Change in Ki67 from pre- versus post-imatinib/cetuximab treated tumors
timeFrame: 6 months after last research biopsy
Secondary outcomes:
measure: Adverse Events that are probably related to CTX and imatinib prior to the start of definitive concurrent chemoradiation therapy or surgical resection
timeFrame: Through study completion, an average of 2 years
measure: Rate of hospital re-admissions
timeFrame: Up to 28 days after surgery
measure: Objective response rate (ORR)
timeFrame: Diagnosis, 48 hours prior to surgery or radiation
measure: Objective response rate (ORR)
timeFrame: Diagnosis, 48 hours prior to surgery or radiation
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Justine Bruce, MD
role: PRINCIPAL_INVESTIGATOR
References: