Combining Neo-adjuvant ATR-inhibition With Nodal SBRT for Early-stage Resectable HPV+ OPSCCs

Phase 2Not Yet RecruitingNCT07578467

John Lukens35 enrolled

Overview

This research study is testing whether a new study drug (called ATRN-119) is safe and effective when combined with a single, highly targeted dose of radiation therapy (called stereotactic body radiation therapy or SBRT) to treat early-stage throat cancer that is caused by HPV. The goal of this study is to treat cancer effectively while reducing side effects and helping patients maintain a better quality of life over the long term. Researchers hope that this approach will be just as successful-or possibly more successful-than current treatments, which already have high cure rates. Participants will: * Take 800mg of ATRN-119 every day for 10 days * Receive 1 treatment (called a "fraction") of SBRT to the neck on day 3 of ATRN-119 dosing. * Keep a short diary to track ATRN-119 dosing. The diary will be provided by study team * Receive standard of care treatment after treatment with ATRN-119 + SBRT including TransOral Robotic Surgery (TORS) to remove the primary tumor with Neck Dissection and adjuvant therapy (if indicated) * Receive additional safety checkups and tests by researchers during routine visits with their cancer doctor for 2 years after study treatment

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HPV Positive Oropharyngeal Squamous Cell Carcinoma Squamous Cell Carcinoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 * Patients that have been diagnosed with HPV-positive throat cancer (OPSCC) at an early stage (stage I or II), confirmed by a biopsy. * Patients' blood calcium level is within a safe range * Patients' blood, kidney, and liver health are strong enough, shown through specific medical test results * If a participant is female, she must not be pregnant or breastfeeding. * If a participant is male, he must agree to use highly effective birth control from the start of the study until a short period after the last dose of the study drug. Exclusion Criteria: * Patients with late-stage tumors (Stage III or IV) * If the cancer has already spread to distant parts of the body (M1) when first diagnosed * Prior advanced head and neck cancer requiring radiation or major surgery * Patients whose original tumor site cannot be identified * Patients that have a known additional malignancy that is progressing or requires active treatment * Patients that had a surgical procedure performed within 7 days prior to first scheduled dose of ATRN-119. This does not include procedures that are used to diagnose or determine extent of study disease (such as biopsies). * Patients taking medications that strongly affect how the body processes certain drugs (CYP enzymes) at the same time as the study treatment. * Patients with active infections and/or receiving systemic antibiotics or anti-viral medications. * Patients with uncontrolled HIV or active hepatitis B or C are usually not eligible. However, those whose infections are well-controlled on treatment for at least a month and meet certain viral load limits can participate * Current or past diagnosis of leukemia within the past 5 years. * Patients with a history of non-malignant gastrointestinal (GI) bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months. * Patient has uncontrolled hypertension at time of enrollment. * Patients who recently had serious kidney problems or kidney disease. * Patients cannot have taken another experimental drug within 30 days-or within a period equal to five times that drug's half-life-before starting this study * Medical illness that, in the opinion of the Investigator, may impact the safety of the patient * Patients who use recreational drugs or have mental health conditions that might make it hard to follow study visits, based on the doctor's judgment. * Known hypersensitivity to ATRN-119 or its ingredients * Patients with serious liver disease or liver problems that could affect how the body processes the study drug * Patients who are fairly limited in daily activities (ECOG score of 2 or higher) * Patients with serious other health problems that the doctor thinks could prevent them from completing the study * Pregnancy or lactation * Inability to provide informed consent

Outcomes

Primary Outcomes

Phase Ib: Feasibility of a neo-adjuvant approach combining ATRN with SBRT before TORS

This will be judged by whether patients are able to have their planned surgery within 6 weeks after the study treatment, and whether there are no problems during surgery that the study doctor believes were caused by the study treatment.

Time frame: Within 6 weeks after study treatment

Phase II: Major pathologic response (MPR) rate of radiated nodal disease

Researchers will measure how many patients have a strong treatment response in the affected lymph nodes that were treated with radiation, based on what is seen when the tissue is examined.

Time frame: Immediately after standard of care primary tumor removal surgery

Secondary Outcomes

Phase II: To assess safety of ATR inhibitor ATRN-119 with nodal SBRT prior to surgery

This will be judged based on whether there are any surgery problems that the study doctor thinks were caused by the earlier treatment, as well as any side effects from the treatment.

Time frame: From start of study treatment through standard of care 2-year Follow-Up visit

Phase II: Radiographic response rates

This looks at how many patients' tumors shrink or improve based on imaging tests like scans. This is assessed by comparing pre- and post- study treatment MRI (or CT) Neck scans using typical descriptive changes noted by a head and neck specialized radiologist.

Time frame: Pre-treatment MRI will be taken prior to enrollment as part of standard of care. Post-treatment Research MRI will be completed 1 week before standard of care tumor removal surgery.

Phase II: Type of adjuvant treatment required

Percentage of patients requiring additional radiation therapy +/- chemotherapy after their main treatment as compared to historic controls (e.g. 75% requiring RT, 25% requiring chemotherapy). Additional therapy is determined by the participant's care team as part of their standard of care treatment, so not all patients will receive additional radiation or chemotherapy.

Time frame: Within 4 months of primary tumor removal surgery

Phase II: Pathologic response of primary tumor and nodal disease

This looks at how strongly the main tumor and the affected lymph nodes respond to treatment. Pathologic response rates will be determined by comparing pre- and post- surgery tumor tissue samples for patients who have enough pre-op tissue to analyze from pathology.

Time frame: Immediately after primary tumor removal surgery

Phase II: Assessment of Patient Reported quality of life

Patients will be asked to take the M.D. Anderson Head \& Neck Symptom Inventory Questionnaire (MDASI-HN) at multiple timepoints throughout the study. The MDASI Head and Neck (MDASI-HN) questionnaire is scored by averaging patient-rated items on a 0-10 scale covering 13 core symptoms, 9 head/neck-specific symptoms, and 6 interference items. Higher scores indicate greater symptom severity and worse interference with daily life.

Time frame: From enrollment to 24 Month Follow-Up Visit