Durvalumab (MEDI4736), Tremelimumab and Palliative Hypofractionated Image Guided Radiation Therapy (HIGRT) in Patients With Recurrent/Metastatic Squamous Cell Carcinomas of the Head and Neck Previously Treated With Immune Checkpoint Inhibitors
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Metastatic Head and Neck Squamous Cell Carcinoma
- Sponsor
- University of Washington
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Number of Patients With Adverse Effects Graded According to Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
This phase I/II trial studies the side effects of durvalumab, tremelimumab and hypofractionated radiation therapy in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving durvalumab, tremelimumab, and hypofractionated radiation therapy may work better in treating patients with recurrent or metastatic head and neck squamous cell carcinoma.
Detailed Description
PRIMARY OBJECTIVE: I. To demonstrate safety and tolerability of durvalumab and tremelimumab and palliative radiation therapy in patients with recurrent metastatic squamous cell carcinomas of the head and neck previously exposed to an anti PD-1 or PDL-1 monoclonal antibody. SECONDARY OBJECTIVES: I. Measure objective response rates based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. criteria in patients receiving the durvalumab, tremelimumab and palliative radiation therapy (RT) combination. II. Determine overall and progression free survival in patients enrolled in the study. OUTLINE: Patients receive tremelimumab intravenously (IV) over 1 hour and durvalumab IV over 1 hour on day 1, week 1. Treatment repeats every 4 weeks for up to 4 cycles or every 6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes on day 1, week 16. Treatment repeats every 4 weeks for up to 9 cycles or every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo hypofractionated radiation therapy using either hypofractionated, image-guided radiotherapy (HIGRT) or stereotactic body radiation therapy (SBRT) over 3 fractions every other day (QOD) during week 3. After completion of study treatment, patients are followed up at 30 days, 2, 3, 4, 6, 8, and 10 months, and then every 12 months.
Investigators
Cristina Rodriguez
Professor
University of Washington
Eligibility Criteria
Inclusion Criteria
- •Histologically proven recurrent/metastatic squamous cell carcinoma arising from a previous head and neck primary site, and located within the head and neck region, lung mediastinum, lymph nodes, soft tissue metastases or bone, and who are not candidates for curative intent therapy
- •An actual body weight \> 40kg
- •Demonstrated disease progression during, or after discontinuation, of the most recent line of systemic therapy
- •Have received any number lines of prior systemic therapy (including systemic therapy in the curative intent setting, and including a platinum containing regimen)
- •Have received an anti-PD1 or anti PDL1 monoclonal antibody
- •Have a target lesion/s deemed suitable by the treating physicians for hypofractionated radiation therapy (HIGRT or SBRT) with the intent of palliation or prevention of symptoms; this lesion must be: a) 1-3 non overlapping sites in the head and neck region OR b) metastatic lesions outside the head and neck (H\&N) region in the lung mediastinum, soft tissue metastases, lymph nodes or bone (a minimum of 1 and a maximum 5 lesions will be irradiated), provided there is no significant overlap between the lesions; patients should have RECIST 1.1 criteria measurable disease in addition to the lesion/s treated with radiation; if the site/s of radiation were previously radiated to high dose RT (\> 50 Gy), there should be \> 6 month time interval between the last dose of radiation and the start of radiation
- •Have the ability to tolerate required radiotherapy-related procedures (e.g.: lie flat and hold position for treatment) as determined by the treating physician
- •Be willing and able to provide written informed consent for the trial and comply with the study visit requirements
- •Have measurable disease based on RECIST 1.
- •(in addition to the lesion/s that will be treated with hypofractionated radiation therapy)
Exclusion Criteria
- •Has a body weight =\< 40kg at the time of enrollment
- •Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
- •Has a target lesion/s for radiotherapy that is \> 5 cm (\> 50 cc) in greatest dimension
- •Has a target lesion/s in a region that previously received high dose radiation therapy (RT) (\> 50 Gy) demonstrating any of the following:
- •carotid artery encasement (\> 180 degrees)
- •unprotected carotid artery (i.e. skin is directly over the carotid without intervening soft tissue, especially after prior neck dissection without a vascularized free flap) (a\&b due to risk of carotid blow out)
- •skin infiltration by tumor (due to risk of fistula)
- •located in the larynx/hypopharynx primaries (due airway threat)
- •treated with high dose radiation therapy (\> 50 Gy) within 6 months or less of trial enrollment
- •Any prior grade \>= 3 immune-related adverse event (irAE) while receiving a prior immunotherapy agent, or any unresolved irAE \> grade 1
Outcomes
Primary Outcomes
Number of Patients With Adverse Effects Graded According to Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0
Time Frame: From the start of study treatment up to 3 months after last study treatment, up to 38 months
Toxicities will be summarized as the number and percentage of patients with each type of toxicity, per Criteria for Adverse Events version 4.0
Secondary Outcomes
- Overall Survival(From the date of study enrollment for up to 2 years)
- Progression-free Survival(From the date of study enrollment for up to 2 years)
- Response Rate(Up to 2 years)