Radiotherapy With Durvalumab Prior to Surgical Resection for HPV Negative Squamous Cell Carcinoma
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|ClinicalTrials.gov Identifier: NCT03635164|
Recruitment Status : Active, not recruiting
First Posted : August 17, 2018
Last Update Posted : May 13, 2022
|Condition or disease||Intervention/treatment||Phase|
|Squamous Cell Carcinoma of the Head and Neck||Drug: Durvalumab Radiation: Stereotactic Body Radiation Therapy (SBRT) Procedure: Standard of Care Therapy||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/Ib Trial of Radiotherapy in Combination With Durvalumab (MEDI4736) Prior to Surgical Resection for HPV Negative Squamous Cell Carcinoma of the Head and Neck (HNSCC)|
|Actual Study Start Date :||November 1, 2018|
|Estimated Primary Completion Date :||May 19, 2023|
|Estimated Study Completion Date :||May 19, 2024|
Experimental: Dose Escalation and Expansion
Part 1 of this trial will use a traditional 3+3 design will be used for this trial (i.e. cohort sizes of 3 patients for the first and second cohort at each dose level). Dose escalation will occur as long as there are minimal dose limiting toxicities.The expectation is that 9 patients will be enrolled to the trial during part 1.This is based on the expectation that all dose levels are safe (i.e. patients will not experience DLTs at all dose levels). The range of patients needed will be 6-12 patients.
Part 2 of this trial will be an expansion cohort. A total of 8 additional patients will be enrolled at the dose level determined to be the MTD in part 1 of the study. These 8 patients will be used to confirm that the MTD is a safe combination, as well as provide additional patients to investigate the efficacy for the treatment combination.
Note: Standard of care surgery will follow 3-6 weeks after medication and radiation treatment.
Patients will receive one dose of neoadjuvant durvalumab 1500 mg approximately 3-6 weeks prior to standard of care surgery. It will be given concurrently with the first dose of radiation (RT). Patients will receive up to six doses of durvalumab and radiation post-operatively.
Radiation: Stereotactic Body Radiation Therapy (SBRT)
The starting RT dose level will be given as 6 Gy for 2 fractions (12 Gy total) every other day over approximately one week to sites of gross disease only to minimize exposure to normal tissue. If toxicity develops and surgery is delayed by more than 8 weeks (qualifying as a DLT), the radiation dose will be dropped per protocol for the next set of patients. If this dose is tolerated, the dose will be increased to 6 Gy for 3 fractions (18 Gy total) for the next 3 patients.
Procedure: Standard of Care Therapy
Patients will proceed to surgical resection 3-6 weeks after radiation as recommended by the ENT surgeon.
- Maximum Tolerated Dose and Dose Limiting Toxicities [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]The Maximum Tolerated Dose (MTD) and Dose Limiting Toxicities (DLT) will be discovered by using the 3+3 study design.
- Pathologic Response [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]Tumor response to neoadjuvant therapy (durvalumab + SBRT) will be assessed by pathology review of the surgical specimen. Response will be labeled as complete pathologic remission, microscopic residual tumor (only scattered foci of residual tumor cells) or macroscopic residual tumor.
- Clinical Response [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]Overall survival (OS), along with locoregional control and distant control will be determined from the time of enrollment to date of death due to any cause. OS will be evaluated by Kaplan-Meier estimate.
- Evaluate Biomarkers: Gene Expression [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]Analysis of gene expression of RNA levels and entire genome sequences using the 10X Genomics single-cell RNA-sequencing platform.
- Evaluate Biomarkers: Phenotypic Analysis [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]Phenotypic analysis of T cells and assessment of intracellular and circulating cytokines using multiplex mass flow cytometry to analyze phenotypic changes, functional response of cytokine production, and activation status of tumor infiltrating lymphocytes (TILs), circulating T cells (especially CD8 and PD-1 expression), and peripheral blood mononuclear cells (PBMCs).
- Evaluate Biomarkers: Immune Cell Infiltration [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]Examination of intratumoral immune cell infiltration using the Perkin Elmer Vectra 3 and tissue microarrays.
- Toxicity Profile [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]Grading of adverse effects (AEs) will follow the guidelines provided in the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
- Short Term Quality of Life [ Time Frame: Study start date to study end date, or death, whichever comes first, up to 24 months ]Short- and long-term quality of life will be obtained using FACT H&N v4 and will be assessed at baseline, with each cycle, post-SBRT, post-surgically, and throughout adjuvant therapy on a standard schedule.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03635164
|United States, Colorado|
|University of Colorado Hospital|
|Aurora, Colorado, United States, 80045|
|Memorial Hospital Central|
|Colorado Springs, Colorado, United States, 80909|
|Poudre Valley Hospital|
|Fort Collins, Colorado, United States, 80524|
|Principal Investigator:||Sana Karam, MD, PhD||University of Colorado, Denver|