Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer. Issue 5 (22nd December 2019)

• Record Type: Journal Article
• Authors: Mayadev, Jyoti; Zamarin, Dmitriy; Deng, Wei; Lankes, Heather; O'Cearbhaill, Roisin; Aghajanian, Carol A; Schilder, Russell
• Is Part Of: International journal of gynecological cancer. Volume 30:Issue 5(2020)
• Page Start: 701
• Page End: 704
• Publication Date: 2019-12-22
• Subjects: Cervical Cancer -- Radiation -- Gynecology; Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2019-001012
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Background: There is a lack of data exploring the use and optimal timing of immunotherapy and chemoradiation therapy (CRT) in node-positive cervical cancer. Further translational research into mechanisms of response and resistance to immunotherapy in advanced cervical cancer is warranted. Primary Objective(s): To determine if sequencing of atezolizumab and CRT result in differential immune activation, as determined by clonal expansion of T cell receptor beta (TCRB) repertoires in peripheral blood on day 21. Study Hypothesis: There is a difference for clonal expansion of T cell receptor beta repertoires in the peripheral blood at day 21 between the priming and concurrent atezolizumab and CRT in Arm A vs the concurrent atezolizumab and CRT in Arm B. Trial Design: Locally advanced cervical cancer patients with lymph node-positive disease will be randomized on this open-label, randomized trial with two experimental arms. Arm A will get one dose of atezolizumab prior to cisplatin CRT, and then two subsequent doses of atezolizumab during the CRT, and Arm B will get three doses during CRT. Patients will be followed for 2 years to assess outcomes. Major Inclusion/Exclusion Criteria: Patients must have histologically confirmed, newly diagnosed advanced cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma): FIGO 2009 clinical stages IB2/IIA with positive para-aortic nodes, or FIGO 2009 clinical stages IIB/IIIB/IVA with positive pelvic or para-aortic lymph nodes. Exclusion criteria include those who had a prior hysterectomy or lymph node dissection. Primary Endpoint(s): Clonal expansion of TCRB) repertoires in peripheral blood on day 21. Sample Size: The sample size will be 40 patients. Estimated Dates for Completing Accrual and Presenting Results: We estimate accrual to finish by the summer of 2020 with presentation of results to follow in 2021. Trial Registration: NCT03738228 .