203TiP - Autophagy as a target for therapy in ovarian cancer: A phase II randomized trial with biomarker correlation (ATOC Trial)

Background

Epithelial ovarian cancer (EOC) is gynecologic cancer with one of the highest mortalities. First-line treatment usually involves cytoreductive surgery and six cycles of platinum and taxane chemotherapy. With this treatment, most (70-80%) patients with stage III/IV disease relapse after one year. Patients who require re-treatment >6 months after previous platinum exposure [platinum sensitive relapsed ovarian cancer (PS-ROC)] are usually treated with a combination containing platinum agent. Autophagy pathways are activated in relapsed ovarian cancer allowing cancer cells to survive chemotherapy-induced stress. Hydroxychloroquine (HCQ) is an autophagy inhibitor that inhibits the autophagosome's fusion with the lysosome.

Trial design

Study design: Randomized Phase II Study Key inclusion criteria: 1. Platinum-sensitive-relapsed-(serous-epithelial)-ovarian cancer. 2. Measurable disease (elevated CA-125 or measurable by Response Evaluation Criteria in Solid Tumors criteria) at the time of study enrolment. 3. Age ≥ 18 years. 4. Eastern Cooperative Oncology Group performance status 0 to 2. 5. Acceptable bone marrow and organ function. Sample Size: The response rate of standard therapy is about 60-65%. Addition of hydroxychloroquine to demonstrate an improvement in response rate of 15% (one-sided alpha: 5%; power: 80%); initial estimate was 56 (n=28 patients in each arm). With a 10% drop-out, the sample size will be 62 (n=31 in each arm). Study Procedure: Eligible patients will be randomized to receive either standard therapy or standard therapy along with hydroxychloroquine (200 mg BD). After the completion of 3 cycles, the patients will be assessed for response. For correlative studies, blood samples will be collected at baseline and end of 3 cycles. Standard Therapy: 3 weekly Carboplatin+ paclitaxel/gemcitabine or weekly paclitaxel+carboplatin Objectives: 1. To compare the response rates of patients after 3 cycles using RECIST 1.1 criteria. 2. To study the biomarkers of autophagy at baseline and after 3 cycles. 3. To study progression-free survival and overall survival. 4. To assess the toxicity. 5. To assess the quality of life at baseline and after 3 cycles.

Clinical trial identification

CTRI/2020/06/025790.

Legal entity responsible for the study

Dr Prasanth Ganesan, Ms Luxitaa Goenka, JIPMER, Puducherry.

Funding

Indian Council of Medical Research.

Disclosure

All authors have declared no conflicts of interest.