A Phase II Study of Durvalumab (MEDI 4736) With Radiotherapy for the Adjuvant Treatment of Intermediate Risk Head and Neck Squamous Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Larynx
- Sponsor
- UNC Lineberger Comprehensive Cancer Center
- Enrollment
- 18
- Locations
- 3
- Primary Endpoint
- Disease-free Survival Rate
- Status
- Active, Not Recruiting
- Last Updated
- 9 months ago
Overview
Brief 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.
Detailed 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. Consent for the use of any residual material from biopsy (archival tissue) and serial blood draws will be required for enrollment.
- •Age ≥ 18 years of age on day of signing informed consent
- •ECOG Performance Status of 0 or 1 (See Appendix 12.4: ECOG Performance Status)
- •Histologically confirmed squamous cell carcinoma of the head and neck, including the following subtypes: oral cavity, oropharynx, hypopharynx, larynx
- •Must have undergone gross total resection of the primary tumor with curative intent within the past 8 weeks with surgical pathology demonstrating ≥ 1 of the following criteria for "intermediate" risk of recurrence:
- •perineural invasion
- •lymphovascular invasion
- •single lymph node \> 3 cm or at least 2 nodes without evidence of extracapsular extension
- •close margins defined as \< 5 mm but not frankly positive (in the case of ambiguous, controversial, or superseded margins, final clinical assessment regarding margin status will prevail)
- •pathologically confirmed T3 or T4 primary tumor
Exclusion Criteria
- •Subjects meeting any of the following exclusion criteria will not be able to participate in this study:
- •Is currently participating in or has participated in a study of an investigational agent or an investigational device within 4 weeks of the first dose of treatment.
- •Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
- •Has evidence of metastatic disease at time of diagnosis
- •Is receiving concurrent chemotherapy, investigational drug, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- •Treatment with any investigational drug within 28 days or 5 half-lives of Day 1 of treatment on this study, whichever is shortest.
- •Has not received any antibiotics \<7 days prior to 1st dose of durvalumab. If the patient receives either IV antibiotics or \>5 day treatment course (oral or IV), then the 1st durvalumab dose should not be given until 14 days of last antibiotic dose. During eligibility screening, subjects who receive any antibiotics within 30 days prior to the proposed initial infusion of durvalumab should be flagged and reviewed by the site's Principle Investigator to determine if the subject is a good candidate to receive durvalumab.
- •Known allergy or hypersensitivity to durvalumab or any of the study drug excipients.
- •Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
Arms & Interventions
Open-label, single-arm
Durvalumab in combination with intensity modulated radiotherapy (IMRT) treatments
Intervention: Durvalumab
Open-label, single-arm
Durvalumab in combination with intensity modulated radiotherapy (IMRT) treatments
Intervention: Intensity Modulated Radiotherapy Treatments
Outcomes
Primary Outcomes
Disease-free Survival Rate
Time Frame: 3 years
Disease-free Survival Rate (DFS) defined as the percentage of participants who were disease-free and alive at 3 years, counting the time from day 1 of treatment to time of disease recurrence or death, was calculated based on the Kaplan-Meier method.
Secondary Outcomes
- PD-L1 Expression With Disease Free Survival.(5 years)
- Number of Participants With Grade 3-4 Acute Toxicities(Up to 30 days)
- Chronic Toxicities of Adjuvant Durvalumab With Radiotherapy(12 weeks)
- Overall Survial in Patients With Intermediate-risk HNSCC Treated With Adjuvant Durvalumab With Radiotherapy PD-L1 Expression With Disease Free Survival(5 years)