Testing the Addition of an Anti-Cancer Drug, Camonsertib, to Radiation Therapy for Recurrent Head and Neck Squamous Cell Carcinoma
Phase I Trial of ATR Inhibitor Camonsertib Combined With Stereotactic Body Radiation Therapy for Recurrent Head and Neck Squamous Cell Carcinoma
3 other identifiers
interventional
39
1 country
1
Brief Summary
This phase I trial tests the safety, side effects, and best dose of camonsertib in combination with stereotactic body radiation therapy in controlling disease in patients with head and neck squamous cell cancer that has come back after a period of improvement (recurrent) or that cannot be removed by surgery (unresectable). Camonsertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Stereotactic body radiation therapy is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Giving camonsertib in combination with stereotactic body radiation therapy may help control disease in patients with recurrent or unresectable head and neck squamous cell cancers.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2027
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 4, 2025
CompletedFirst Posted
Study publicly available on registry
September 5, 2025
CompletedStudy Start
First participant enrolled
February 13, 2027
ExpectedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2029
Study Completion
Last participant's last visit for all outcomes
May 31, 2029
June 11, 2026
June 1, 2026
2.3 years
September 4, 2025
June 10, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Incidence of adverse events (AEs)
The safety and tolerability of camonsertib will be evaluated during the dose escalation phase. The frequency and percentage of AEs will be provided overall and by dose level for any grade and attribution as well as for grade 3 or greater AEs, at least possibly related to treatment.
During dose escalation phase
Maximum tolerated dose (MTD) of camonsertib and concurrent stereotactic body radiation therapy (SBRT) reirradiation
The dose-escalation phase will utilize a Bayesian Optimal Interval Design to determine the MTD for combined camonsertib and SBRT.
During dose escalation phase
Incidence of late toxicities (dose expansion phase)
The proportions of total patients experiencing late toxicities will be estimated. The frequency and percentage of AEs will be provided overall and by dose level for any grade and attribution as well as for grade 3 or greater AEs, at least possibly related to treatment.
Within 1 year of treatment initiation
Secondary Outcomes (2)
Overall response rate
Up to 55 weeks
Progression-free survival (PFS)
From the start of treatment regimen until documented local or distal failure or death from any cause, assessed up to 55 weeks
Other Outcomes (2)
Biomarkers of response
Up to 55 weeks
Pharmacokinetic data
Day 1: Pre, and 0.5, 1, 1.5, 2, 4, 6, and 8 hour post and Day 2: 24 hour after dose 1, pre-dose 2
Study Arms (1)
Treatment (camonsertib, SBRT)
EXPERIMENTALPatients undergo 4 or 5 treatment fractions of SBRT twice weekly, 2-3 days apart between fractions, over 3 weeks. Patients receive camonsertib PO QD on the day of and the day after each radiation therapy treatment. Patients also undergo PET/CT or CT and collection of blood samples throughout the trial.
Interventions
Undergo PET/CT
Undergo SBRT
Undergo collection of blood samples
Given PO
Undergo CT or PET/CT
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed recurrent or metachronous (second primary) unresectable head and neck squamous cell carcinoma involving the oral cavity, oropharynx, larynx, hypopharynx, and/or paranasal sinus, or cervical lymphadenopathy with unknown primary. Core needle biopsy (preferably at least three 18-gauge cores) or incisional biopsy is preferred over fine needle aspiration (FNA) for diagnosis of recurrent disease or new primary head and neck squamous cell carcinoma to provide sufficient tumor tissue for correlative studies. Unresectable refers both to patients who have declined surgery and patients deemed unresectable by otolaryngology. This includes patients for whom curative resection is medically contraindicated and/or would be associated with excessive surgical risk (as deemed by the consulting otolaryngologist) or undue surgical morbidity (e.g., total glossectomy, laryngectomy, and/or major resection requiring free flap reconstruction). There are no requirements related to prior systemic therapies that patients may have received
- Patients must have recurrent disease within a previously irradiated area (radiotherapy to dose ≥ 30 gray \[Gy\] and ≤ 80 Gy; in-field recurrence)
- Patients must have completed prior radiotherapy at least 6 months prior to enrollment. Due to safety concerns, reirradiation within less than 6 months to the head and neck is very rarely recommended per standard of care
- Patients must have measurable disease (at least one measurable lesion) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Baseline imaging must include neck CT (preferably contrast-enhanced) and chest CT or skullbase to midthigh PET/CT (preferably with contrast-enhanced neck CT if diagnostic contrast-enhanced neck CT not available). Patients who have undergone surgery aside from biopsy may be included if gross disease is present within the surgical resection bed or at another site
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of camonsertib in combination with radiotherapy in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- Leukocyte count ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin dependency (within 7 days of assessment)
- Serum bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (if total serum bilirubin \> 1.5 × institutional ULN, then direct bilirubin must be \< ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 × institutional ULN
- Albumin \> 2.5 mg/dL
- Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2
- GFR can be measured directly or estimated using the site's institutional standards
- +8 more criteria
You may not qualify if:
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1), with the exception of alopecia
- Patients who are receiving any other investigational agents for a current cancer diagnosis
- Patients with distant metastatic disease
- Patients who have received more than one prior course of head and neck radiotherapy overlapping the region to be treated with the current diagnosis of head and neck cancer
- Patients who have disease surrounding \> 180 degrees of the carotid artery
- Patients with tumors invading the mandible or tumors with gross skin involvement (i.e., tumor ulceration through the skin)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to camonsertib or radiation
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
- Pregnant women are excluded from this study because camonsertib is an ATR inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with camonsertib, breastfeeding should be discontinued if the mother is treated with camonsertib. These potential risks may also apply to other agents used in this study
- Patients diagnosed with scleroderma
- Concomitant use of strong CYP3A4/5 inhibitors and inducers, and strong P-gp and BCRP inhibitors
- Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
UPMC Hillman Cancer Center LAO
Pittsburgh, Pennsylvania, 15232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yvonne M Mowery
UPMC Hillman Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 4, 2025
First Posted
September 5, 2025
Study Start (Estimated)
February 13, 2027
Primary Completion (Estimated)
May 31, 2029
Study Completion (Estimated)
May 31, 2029
Last Updated
June 11, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.