Durvalumab With Radiotherapy for Adjuvant Treatment of Intermediate Risk SCCHN

Oral Cancer Clinical Trial

Official title: A Phase II Study of Durvalumab (MEDI 4736) With Radiotherapy for the Adjuvant Treatment of Intermediate Risk Head and Neck Squamous Cell Carcinoma

Status Active, not recruiting

Clinical Trial Summary

The purpose of this study is to investigate other drugs that may be combined with radiation to treat cancer. The study focuses on determining whether a combination of durvalumab with radiation can both improve cure rate and at the same time have less serious side effects. Throughout this document, this investigational drug will be referred to as the "study drug", or named individually (durvalumab). The study drug in this research is referred to as investigational because the U.S. Food and Drug Administration (FDA) has not yet approved itfor the treatment of head and neck cancer. Durvalumab was FDA approved in 2017 for the treatment of certain types of bladder cancer, but has not been approved for use in Head and Neck cancer patients.

Durvalumab is an experimental drug that uses the body's immune system to fight the cancer. This study drug is being used in other ongoing clinical trials for other types of cancers. The doctor feels that a patient may experience fewer side effects using this study drug with radiation rather than using cisplatin. The doctor is also investigating whether using this drug can increase the effectiveness of treatment.

Clinical Trial Description

Primary Objective -To estimate median 3-year disease free survival (DFS) in patients with intermediate-risk HNSCC treated with adjuvant durvalumab with radiotherapy.

Secondary Objectives

• To characterize safety by evaluating Grade 3-4 acute toxicities of adjuvant durvalumab with radiotherapy in intermediate-risk HNSCC patients

• To characterize the Grade 3-4 chronic toxicities of adjuvant durvalumab with radiotherapy in intermediate-risk HNSCC patients.

• To characterize any-grade chronic toxicities of adjuvant durvalumab with radiotherapy in intermediate-risk HNSCC patients.

• To estimate median OS in patients with intermediate-risk HNSCC treated with adjuvant durvalumab with radiotherapy.

• To correlate PD-L1 expression with disease free survival

Exploratory Objectives

• To analyze disease free survival by HPV status

• To determine how treatment with adjuvant durvalumab and radiotherapy changes markers of tumor infiltrating lymphocytes (TIL)

Primary Endpoint

-3-year DFS will be estimated via the Kaplan-Meier method. DFS is defined as the time from D1 of treatment to time of disease recurrence or death

Secondary Endpoints

• Grade 3-5 acute toxicity will be evaluated according to guidelines from NCI CTCAE, v5.0 and include toxicity from the first day of treatment with immunotherapy until 30 days after completion of concurrent immunotherapy and radiation. Toxicity will include all toxicity attributed to the total study regimen (inclusive of radiation) not just to durvalumab alone.

• Grade chronic 3-5 toxicity will be evaluated according to guidelines from NCI CTCAE, v5.0 and include toxicity continuing or occurring 30 days after completion of concurrent immunotherapy and radiation, and will be followed for up to 6 months.

• OS will be estimated via the Kaplan-Meier method. OS is defined as the time from D1 of treatment to death from any cause.

• Measure PD-LI expression by immunohistochemistry. Pre-treatment PD-L1 expression will be correlated with disease free survival following treatment of adjuvant durvalumab with radiotherapy.

Exploratory Endpoints

• Measure HPV status. HPV status will be correlated with disease free survival following treatment of adjuvant durvalumab with radiotherapy

• Measure tumor infiltrating lymphocytes (TIL) by flow cytometry at baseline (post-surgical, pre-treatment tissue) and at disease progression (post-treatment tissue). Changes in TIL levels will be compared between these two time points.

Treatment Dosage This Phase II trial will evaluate the combination of durvalumab with radiation therapy as post-operative therapy in intermediate risk patients with HNSCC. All patients will receive durvalumab and radiation therapy during cycles 1-3. Radiation therapy is administered per standard radiation oncology regimens, on a daily basis and/or as scheduled during a Monday-Friday working week. Radiation therapy is given concurrently with durvalumab during Cycles 1-3. Durvalumab treatment (1500 mg Q3W) Cycles 1-3 are 3-weeks long cycles (total of 9 weeks). Radiation therapy will be delivered at a dose of 2 Gy over 30 fractions totalling a final dose of 60 Gy. Radiation treatment will take 6 weeks (Mon-Fri) or 30 days and will occur for 6 of 9 weeks that define Cycles 1-3. However, due to delays or missed appointments, completion of those 30 fractions may take longer than the allotted 6 weeks and this is allowed. Radiation therapy must be scheduled and completed within Cycles 1-3 and should not extend into Cycle 4. Please refer to Section 6.2 for additional details and allowances.

During Cycle 4-6, only durvalumab 1500mg Q4W will be given.

Duration of Follow Up All patients will be followed for up to 5 years, or until death, whichever occurs first after removal from study treatment for determination of study endpoints. Patients removed from study treatment for unacceptable adverse event (AE)s will be followed for resolution or stabilization of the adverse event(s). All patients (including those withdrawn for AEs) should be followed after removal from study treatment as stipulated in the protocol. ;

Related Conditions & MeSH terms

• Digestive Organs--Diseases
• Larynx
• Lip
• Mouth Neoplasms
• Oral Cancer

• NCT number: NCT03529422
• Study type: Interventional
• Source: UNC Lineberger Comprehensive Cancer Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 7, 2019
• Completion date: May 6, 2026