Stereotactic Body Radiation Therapy, Tremelimumab and Durvalumab in Treating Participants With Recurrent or Metastatic Cervical, Vaginal, or Vulvar Cancers
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|ClinicalTrials.gov Identifier: NCT03452332|
Recruitment Status : Recruiting
First Posted : March 2, 2018
Last Update Posted : August 21, 2019
|Condition or disease||Intervention/treatment||Phase|
|Human Papillomavirus Positive Human Papillomavirus-Related Cervical Squamous Cell Carcinoma Human Papillomavirus-Related Vulvar Squamous Cell Carcinoma Metastatic Cervical Adenocarcinoma Metastatic Cervical Carcinoma Metastatic Cervical Squamous Cell Carcinoma, Not Otherwise Specified Metastatic Vaginal Adenocarcinoma Metastatic Vaginal Carcinoma Metastatic Vulvar Carcinoma Recurrent Cervical Carcinoma Recurrent Vaginal Carcinoma Recurrent Vulvar Carcinoma Stage IV Cervical Cancer AJCC v8 Stage IV Vaginal Cancer AJCC v8 Stage IV Vulvar Cancer AJCC v8 Stage IVA Cervical Cancer AJCC v8 Stage IVA Vaginal Cancer AJCC v8 Stage IVA Vulvar Cancer AJCC v8 Stage IVB Cervical Cancer AJCC v8 Stage IVB Vaginal Cancer AJCC v8 Stage IVB Vulvar Cancer AJCC v8 Vaginal Squamous Cell Carcinoma, Not Otherwise Specified Vulvar Adenocarcinoma||Biological: Durvalumab Other: Laboratory Biomarker Analysis Radiation: Stereotactic Radiosurgery Biological: Tremelimumab||Phase 1|
I. To determine the safety, and tolerability of combined immune checkpoint blockade with 3 fractions of stereotactic body radiation therapy (stereotactic ablative radiotherapy [SABR]) of up to two metastatic lesions in patients with recurrent and or metastatic cervical, vaginal, or vulvar cancer.
I. To evaluate clinical response rates and assess toxicities of treatment to durvalumab combined with tremelimumab with 3 fractions of SABR of at least one and up to two metastatic lesions in patients with recurrent/metastatic cervical, vaginal, or vulvar cancer.
II. To estimate progression-free survival, overall survival, and time to next treatment.
III. Evaluate biomarkers of response to immune checkpoint inhibition combined with SABR in biopsies of metastases and serum collected at time points during treatment.
I. To evaluate potential biomarkers of immune response to combined immune-checkpoint inhibition with SABR and correlate this with clinical response to treatment.
II. To evaluate potential biomarkers of immune response including cervical and rectal microbial diversity, cervical immune cell infiltration and peripheral immune cell activation as correlates of clinical response to treatment.
Participants receive tremelimumab intravenously (IV) over 1 hour followed by durvalumab IV over 1 hour on day 1 of each cycle. Participants also undergo SABR over 30-45 minutes on days 8, 10, and 12 of cycle 1. Treatment with tremelimumab repeats every 4 weeks for up to 4 cycles, and treatment with durvalumab repeats every 4 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 30 days, at 2, 3, 4, 6, 8, 10, and 12 months, and then every 6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Multi-Center Study of Stereotactic Ablative Radiotherapy (SABR) in Combination With Durvalumab and Tremelimumab in Patients With Recurrent/Metastatic Advanced Cervical, Vaginal, or Vulvar Cancer|
|Actual Study Start Date :||July 18, 2018|
|Estimated Primary Completion Date :||October 31, 2019|
|Estimated Study Completion Date :||October 31, 2020|
Experimental: Treatment (tremelimumab, durvalumab, SABR)
Participants receive tremelimumab IV over 1 hour followed by durvalumab IV over 1 hour on day 1 of each cycle. Participants also undergo SABR over 30-45 minutes on days 8, 10, and 12 of cycle 1. Treatment with tremelimumab repeats every 4 weeks for up to 4 cycles, and treatment with durvalumab repeats every 4 weeks for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Radiation: Stereotactic Radiosurgery
- Incidence of adverse events by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03 [ Time Frame: Up to 3 months after last dose of durvalumab ]Will be assessed based on dose limiting toxicities (DLTs) and based on adverse events (AEs) throughout the entire treatment period. In the overall assessment of adverse events, AEs will be tabulated by body system, type and grade, overall and by disease cohort. The number and percentage of patients experiencing at least one grade 3 or higher AE will also be reported.
- Response to treatment by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune-related response criteria [ Time Frame: Up to 1 year ]This will be measured in both treated and untreated lesions with computed tomography (CT) imaging or other appropriate imaging modalities. Immune-related response is reported as number and percent of patients with two-sided 80% confidence intervals (CI). Because each patient will have multiple lesions, a generalized linear mixed model will be used, if possible, to calculate overall response, as well as response by index or non-index lesion. The depth and duration of response will be depicted using waterfall and swimmer plots.
- Progression-Free Survival [ Time Frame: From the start of therapy up to first documented disease progression or death from any cause, assessed up to 1 year ]To summarize progression free survival we will use Kaplan Meier analysis, reporting the median with confidence interval.
- Overall Survival [ Time Frame: From start of therapy to death from any cause, assessed up to 1 year ]To summarize overall survival we will use Kaplan Meier analysis, reporting the median with confidence interval.
- Time to next treatment (TTNT) [ Time Frame: From the end of immune-checkpoint inhibition treatment to institution of next therapy, assessed up to 1 year ]To summarize time to next treatment we will use Kaplan Meier analysis, reporting the median with confidence interval.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03452332
|Contact: Lilie L. Lin, MDemail@example.com|
|United States, Texas|
|UT Southwestern/Simmons Cancer Center-Dallas||Not yet recruiting|
|Dallas, Texas, United States, 75390|
|Contact: Kevin V. Albuquerque 214-645-8585 firstname.lastname@example.org|
|Principal Investigator: Kevin V. Albuquerque|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Lilie L. Lin 713-563-2300|
|Principal Investigator: Lilie L. Lin|
|Principal Investigator:||Lilie L Lin||M.D. Anderson Cancer Center|