Recruiting

Phase 1

Camonsertib & Stereotactic Body Radiation TherapyTesting the Addition of an Anti-Cancer Drug, Camonsertib, to Radiation Therapy for Recurrent Head and Neck Squamous Cell Carcinoma

Sponsor:

National Cancer Institute (NCI)

Code:

NCT07156227

Conditions

Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Recurrent Head and Neck Squamous Cell Carcinoma

Recurrent Hypopharyngeal Squamous Cell Carcinoma

Recurrent Laryngeal Squamous Cell Carcinoma

Recurrent Oral Cavity Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Camonsertib

Computed Tomography

Positron Emission Tomography

Stereotactic Body Radiation Therapy

Study Details

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.

Conditions

Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Recurrent Head and Neck Squamous Cell Carcinoma

Recurrent Hypopharyngeal Squamous Cell Carcinoma

Recurrent Laryngeal Squamous Cell Carcinoma

Recurrent Oral Cavity Squamous Cell Carcinoma

Study ID

NCT07156227

Start date

Feb 13, 2027

Status verified date

Jul, 2026

Completion date

May 31, 2029

Anticipated

Primary completion date

May 31, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
Ability to take pills by mouth
The effects of camonsertib on the developing human fetus are unknown. For this reason and because ATR inhibitors and radiation are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after completion of camonsertib administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Exclusion Criteria:

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

Study Design

Enrollment

39 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (camonsertib, SBRT)

Patients 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

Biospecimen Collection

Undergo collection of blood samples

Camonsertib

Given PO

Computed Tomography

Undergo CT or PET/CT

Positron Emission Tomography

Undergo PET/CT

Stereotactic Body Radiation Therapy

Undergo SBRT

Primary outcome measure

Incidence of adverse events (AEs) [ Time Frame: During dose escalation phase ]
Maximum tolerated dose (MTD) of camonsertib and concurrent stereotactic body radiation therapy (SBRT) reirradiation [ Time Frame: During dose escalation phase ]
Incidence of late toxicities (dose expansion phase) [ Time Frame: Within 1 year of treatment initiation ]

Central Contacts and Locations

Locations

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

Contacts

Site Public Contact

800-826-4673 becomingapatient@coh.org

Principal Investigator:

Sean Maroongroge

City of Hope at Irvine Lennar

Recruiting

Irvine, California, United States, 92618

Contacts

Site Public Contact

877-467-3411

Principal Investigator:

Sean Maroongroge

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Yvonne M. Mowery

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 3, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-03.