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

Official title

A Phase Ib/II Study Combining Neo-adjuvant ATR-inhibition With Nodal SBRT for Early-stage Resectable HPV+ OPSCCs

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

Interventions

• Drug ATRN-119
  ATRN-119 at 800 mg QD (every day) for 10 days
• Radiation Stereotactic Body Radiation Therapy (SBRT)
  10 Gy administered to nodal disease (neck) only on day 3 of ATRN-119 dosing

Primary outcome measures

• Phase Ib: Feasibility of a neo-adjuvant approach combining ATRN with SBRT before TORS [Time frame: Within 6 weeks after study treatment]
• Phase II: Major pathologic response (MPR) rate of radiated nodal disease [Time frame: Immediately after standard of care primary tumor removal surgery]

Secondary outcome measures (5)

• Phase II: To assess safety of ATR inhibitor ATRN-119 with nodal SBRT prior to surgery [Time frame: From start of study treatment through standard of care 2-year Follow-Up visit]
• Phase II: Radiographic response rates [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 [Time frame: Within 4 months of primary tumor removal surgery]
• Phase II: Pathologic response of primary tumor and nodal disease [Time frame: Immediately after primary tumor removal surgery]
• Phase II: Assessment of Patient Reported quality of life [Time frame: From enrollment to 24 Month Follow-Up Visit]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07578467 · 15325

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗