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 objectives: 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 endpoints: 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.
Keywords: Cervical Cancer; Gynecology; Radiation.
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