Molecular Residual Disease Interception in Locoregionally-Advanced High Risk HPV+ and HPV- HNSCC

Phase 2

Recruiting

• Conditions: Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA-HNSCC)
• Interventions: Biological: AZD2936

• Registration Number: NCT05414032
• Lead Sponsor: University Health Network, Toronto

Brief Summary

This is a phase II, open-label study to assess the efficacy of AZD2936 in terms of molecular residual disease (MRD) clearance and treatment outcome in patients with MRD after definitive treatment for high risk locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). MRD is defined as ctDNA detection in plasma after definitive treatment. Approximately 200 patients are expected to be enrolled.

Detailed Description

This is a phase II, open-label study to assess the efficacy of AZD2936 in terms of molecular residual disease (MRD) clearance and treatment outcome in patients with MRD after definitive treatment for high risk locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). MRD is defined as ctDNA detection in plasma after definitive treatment. Approximately 200 patients are expected to be enrolled.

The study is divided in 5 parts:

Part A and Part B are common for all patients in the study, which are defined as the periods of definitive treatment and post definitive treatment. Definitive treatment will be either surgery followed by radiation or chemoradiation; definitive radiation or definitive chemoradiation according to standard of care (SOC) in our institution. A baseline ctDNA sample collection and CT staging will be done before treatment. ctDNA analysis will be performed in Part B at approximately week 5 and at week 10 of this period, and patients will be classified as MRD positive or MRD negative based on the week 10 results. If a patient has equivocal results, a new sample will be taken around week 14. Patients who receive surgery as part of their treatment, will also get ctDNA analysis post-surgery.

Part C is the randomized and interventional part of the study (n=60) for patients with MRD. The patient will be randomized 3:1 to Arm A (treatment with AZD2936) or Arm B (observation). Patients in Arm A will continue treatment until the occurrence of any of these circumstances: after completion of 6 cycles, intolerable toxicity or patient decision. ctDNA analysis will be done at week 10 of Part C.

Part D is the follow up part for patients with MRD. Two ctDNA samples will be analyzed at week 2 and at week 10 of Part D. Plasma samples will be collected every 6 months for the first 3 years and a final sample will be also collected if the patient has radiological or clinical progression. A CT/MRI scan will be performed at week 2 of Part D and, if clinically needed, according to SOC.

Part E is the observational follow up part for patients without MRD. A ctDNA sample will be collected at the time of the first follow up and at radiological or clinical progression if applicable.

Study Timeline

• Study First Submitted: 2022-05-26
• Study First Submitted QC: 2022-06-07
• Study First Posted: 2022-06-10
• Study Start: 2023-07-12
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-23
• Last Update Posted: 2023-10-25
• Primary Completion: 2026-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MRD positive Cohort - Arm A (treatment)	AZD2936	Dose formulation- AZD2936 is supplied as a liquid drug product in a 20R vial containing 750 mg (nominal) of active AZD2936. The solution contains 50 mg/mL AZD2936 in 20 mM L-histidine/L- histidine-hydrochloride, 240 mM sucrose, 0.04% (w/v) poloxamer 188, at pH 6.0. Unit dose strength(s)- 750 mg/vial (50 mg/mL) Dosage levels- 750mg administered Q3W Route of administration- IV infusion over 1 hour

Primary Outcome Measures

Name	Time	Method
Efficacy (in terms of ctDNA clearance) of AZD2936 compared to observation (Standard of Care, SOC) in LA-HNSCC patients who have MRD (MRD+) after definitive treatment.	3 years	Clearance of bespoke ctDNA at different time points (week 2 and week 10 after the end of MRD treatment). ctDNA clearance is defined as no detection of ctDNA in both of these two consecutive determinations.

Secondary Outcome Measures

Name	Time	Method
Efficacy (in terms of delaying or preventing radiological recurrence of disease or death) of AZD2936 compared to observation (SOC) in MRD+ LA-HNSCC patients after definitive treatment.	3 years	Disease free survival (DFS) at 12 months.
Safety and tolerability of AZD2936 in MRD+ LA-HNSCC patients after definitive treatment and randomized to receive this combination.	3 years	* Number and severity of treatment related adverse events according to CTCAE v5.0.; * Percentage of participants with AEs, SAEs and rate of AZD2936 discontinuation due to toxicity.
Efficacy (in terms of MRD control) of AZD2936 compared to observation (SOC) in MRD+ LA-HNSCC patients after definitive treatment.	3 years	Time to MRD control failure in MRD+ patients. MRD control failure is defined as two consecutive increases in ctDNA levels (week 2 and week 10 in Part D).
Efficacy (in terms of median DFS and OS) of AZD2936 compared to observation (SOC) in MRD+ LA-HNSCC patients after definitive treatment.	3 years	Median DFS and OS in MRD+ patients.

Trial Locations

Locations (1)

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Canada