207TiP - A two-arm randomized open-label prospective design superiority phase III clinical trial to compare the efficacy of docetaxel-oxaliplatin-capecitabine/ 5 -fluorouracil (DOC/F) followed by docetaxel versus CAPOX/mFOLFOX-7 in advanced gastric cancers

Background

Chemotherapy is the mainstay of treatment in advanced gastroesophageal junction and gastric (GEJ/G) adenocarcinomas, with some additional role for targeted therapy and immunotherapy in select subsets. The choice of optimal chemotherapy in this setting remains undecided, especially with regard to the addition of docetaxel to a FOLFOX/CAPOX (doublet combination) backbone in improving outcomes. Additionally, there is also equipoise with regard to continuing palliative chemotherapy beyond six months in patients with these cancers.

Trial design

The DOC GC study in a multicentric open-label, randomised controlled phase III trial, in adults (age >=18 years) with unresectable/metastatic GEJ/G adenocarcinoma and adequate end-organ function. Patients will undergo randomization to one of two arms: Arm A (Doublet regimen)- modified CAPOX (3 weekly) or modified FOLFOX-7 ( 2 weekly) for a maximum of 6 months and then observation or Arm B (Tripet regimen): modified FLOT (5-FU/leucovorin /Oxaliplatin/Docetaxel) or DOX (docetaxel/oxaliplatin/capecitabine) every 2 weeks for a maximum of four months followed by Docetaxel (60mg/m2) every 3 weeks till disease progression, unacceptable toxicity, or patients choice The primary endpoint of the study is Overall survival (OS), as calculated by Kaplan-Meier method, while key secondary endpoints include Progression-free survival, adverse event rates, and quality of life. Next-generation sequencing is being conducted on all biopsy specimens and patient data will be classified as per the Asian Cancer Research Group classification of gastric cancers based on sequencing. Assuming the median OS with mFOLFOX/CAPOX is 11 months, the study with a power of 80% with a two-sided alpha of 5% requires 162 patients per arm to show a superiority in terms of OS of 5 months with modified FLOT/DOX by the log-rank test method. A total of 211 events are required in the entire study for this analysis to be feasible with a hazard ratio of 0.68. We have assumed a uniform accrual period of 38 months and further 16 months of follow-up.

Clinical trial identification

Clinical Trials Registry-India (CTRI) number: CTRI/2020/03/023944.

Legal entity responsible for the study

The authors.

Funding

TMC research administrative council Nag Foundation Metta Life Sciences Private Limited Indian Cooperative Oncology Network (ICON).

Disclosure

P.G. Bhargava: Financial Interests, Institutional, Invited Speaker: Novartis, Intas, Roche, Pfizer; Financial Interests, Institutional, Advisory Board: Mankind, Zydus. A. Ramaswamy: Financial Interests, Institutional, Research Grant: Cipla Health Limited, Dr Reddy Laboratories, Zydus Lifesciences. A. Kapoor: Financial Interests, Institutional, Local PI: AstraZeneca, Novartis, Beyer Pharmaceuticals, Biocon. V. Noronha: Financial Interests, Institutional, Local PI, Research funding paid to the institution: Amgen, Sanofi India Ltd., AstraZeneca Pharma India Ltd.; Financial Interests, Institutional, Funding, Research funding paid to the institution: Dr. Reddy's Laboratories Inc., Intas Pharmaceuticals. N.S. Menon: Financial Interests, Institutional, Invited Speaker, Outside Submitted work: BMS; Financial Interests, Institutional, Local PI, Outside the submittred workLocal (site ) PI for Destiny Lung -04 trial: AstraZeneca; Financial Interests, Institutional, Local PI, Outside submitted work Local PI for PROSpect study (to determine the prevalence of HRRm in Indian mCRPC patients).: AstraZeneca; Financial Interests, Institutional, Local PI, Local PI for phase 3 ASIAD-3 trial: AURIGENE. K. Prabhash: Financial Interests, Institutional, Advisory Board, fund was received by institution: novartis, merick; Financial Interests, Institutional, Local PI, money for trial purpose come to institution only: roche; Financial Interests, Institutional, Local PI, all fund come to institution: alkem; Financial Interests, Institutional, Local PI, all fund came to tmh: john and johnson. V.S. Ostwal: Financial Interests, Institutional, Advisory Board: Panacea, Reddy's Lab pvt limited, AstraZeneca, Zydus Cadila, Natco; Financial Interests, Personal, Invited Speaker, Expenses for travel and accommodation: AstraZeneca; Financial Interests, Personal, Advisory Board, travel and accommodation arrangements: Natco; Financial Interests, Personal, Advisory Board, Travel and accommodation arrangements: Lupin; Financial Interests, Institutional, Funding, Educational Grant: Reddy's Lab, Zydus Cadila; Financial Interests, Institutional, Other, Drug support: Intas Pharma pvt ltd, Esai Pharma, Alkem pvt ltd; Financial Interests, Institutional, Other, drug support: Micro Labs private limited; Non-Financial Interests, Personal, Leadership Role, CHURCH LEADERSHIP DEVELOPMENT ACTIVITIES: EVERY NATION MUMBAI INDIA; Non-Financial Interests, Personal, Leadership Role, secretary of Supportive care organization in India: Indian Association of supportive care in Cancer. All other authors have declared no conflicts of interest.