Study of ONO-4538 in Gastric Cancer

• ClinicalTrials.gov Identifier: NCT02746796
• Recruitment Status: Active, not recruiting
• First Posted: April 21, 2016
• Last Update Posted: March 22, 2021
• Sponsor: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Ono Pharmaceutical Co. Ltd

Tracking Information

• First Submitted Date: March 29, 2016
• First Posted Date: April 21, 2016
• Last Update Posted Date: March 22, 2021
• Actual Study Start Date: March 2016
• Actual Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2017)

• Progression-free survival (central assessment by IRRC) (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 48 months) ]
• Overall survival (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 54 months) ]

• Original Primary Outcome Measures (submitted: April 18, 2016): Objective response rate (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 12 weeks) ]

Current Secondary Outcome Measures (submitted: February 28, 2017)

• Objective response rate (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 54 months) ]
• Progression-free survival (assessment by the site investigator)(only Part 2) [ Time Frame: Up to study completion (estimated time frame: 54 months) ]
• Duration of response (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 54 months) ]
• Disease control rate (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 54 months) ]
• Time to response (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 54 months) ]
• Best overall response (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 54 months) ]
• Percent change in the sum of diameters of target lesions (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 54 months) ]
• Safety will be analyzed through the incidence of adverse events, serious adverse events [ Time Frame: Up to 28 days from last dose ]
• Safety will be analyzed through the incidence of laboratory abnormalities [ Time Frame: Up to 28 days from last dose ]

Original Secondary Outcome Measures (submitted: April 18, 2016)

• Overall survival (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 24 months) ]
• Progression-free survival (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 24 months) ]
• Duration of response (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 24 months) ]
• Disease control rate (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 24 months) ]
• Time to response (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 24 months) ]
• Best overall response (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 24 months) ]
• Percent change in the sum of diameters of target lesions (only Part 2) [ Time Frame: Up to study completion (estimated time frame: 24 months) ]
• Safety will be analyzed through the incidence of adverse events, serious adverse events [ Time Frame: Up to 28 days from last dose ]
• Safety will be analyzed through the incidence of laboratory abnormalities [ Time Frame: Up to 28 days from last dose ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of ONO-4538 in Gastric Cancer
• Official Title: ONO-4538 Phase II/III Study A Multicenter, Randomized Study in Patients With Unresectable Advanced or Recurrent Gastric Cancer
• Brief Summary: The purpose of study is to evaluate the efficacy and safety of ONO-4538 with chemotherapy in unresectable advanced or recurrent gastric cancer (including esophagogastric junction cancer) not previously treated with the first-line therapy. Part 1 is intended to evaluate the tolerability, safety, and efficacy of ONO-4538 in combination with SOX therapy (Tegafur / gimeracil / oteracil potassium + Oxaliplatin) or CapeOX therapy (Capecitabine + Oxaliplatin). In part 2, the investigator or the subinvestigator will choose a chemotherapy (SOX or CapeOX therapy), taking into account the condition of each subject. Part 2 is planned to evaluate the efficacy and safety of ONO-4538 + chemotherapy in comparison with placebo + chemotherapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Gastric Cancer

Intervention

• Drug: ONO-4538
• Drug: Oxaliplatin
• Drug: Tegafur- Gimeracil-Oteracil potassium
• Drug: Capecitabine
• Drug: Placebo

Study Arms

• Experimental: ONO-4538 + SOX Therapy Cohort (Part 1)

  ONO-4538 360 mg solution intravenously for 30 min in every 3 weeks. Oxaliplatin 130 mg/m2 (BSA) solution intravenously for 2 hours once-daily, followed by 20 days off.

  Tegafur-gimeracil-oteracil potassium combination drug 40 - 60 mg bid orally in 14 days, followed by 7 days off Each drug will be continued until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.

  Interventions:

  • Drug: ONO-4538
  • Drug: Oxaliplatin
  • Drug: Tegafur- Gimeracil-Oteracil potassium
• Experimental: ONO-4538 + CapeOX Therapy Cohort (Part 1)

  ONO-4538 360 mg solution intravenously for 30 min in every 3 weeks. Oxaliplatin 130 mg/m2 (body surface area) solution intravenously for 2 hours once-daily, followed by 20 days off.

  Capecitabine 1200 - 2100 mg bid orally in 14 days, followed by 7 days off. Each drug will be continued until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.

  Interventions:

  • Drug: ONO-4538
  • Drug: Oxaliplatin
  • Drug: Capecitabine
• Experimental: ONO-4538 + chemotherapy group (Part 2)

  With regard to the ONO-4538 + chemotherapy group, either SOX therapy or CapeOX therapy will be selected as the chemotherapy by the investigator or the subinvestigator, taking into account the condition of each subject.

  ONO-4538 360 mg solution intravenously for 30 min in every 3 weeks. Oxaliplatin 130 mg/m2 (body surface area) solution intravenously for 2 hours once-daily, followed by 20 days off.

  Tegafur-gimeracil-oteracil potassium combination drug 40 - 60 mg bid or Capecitabine 1000 mg/ m2 (body surface area) bid orally in 14 days, followed by 7 days off.

  Each drug will be continued until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.

  Interventions:

  • Drug: ONO-4538
  • Drug: Oxaliplatin
  • Drug: Tegafur- Gimeracil-Oteracil potassium
  • Drug: Capecitabine
• Placebo Comparator: Placebo + Chemotherapy group (Part 2)

  With regard to the placebo + chemotherapy group, either SOX therapy or CapeOX therapy will be selected as the chemotherapy by the investigator or the subinvestigator, taking into account the condition of each subject.

  Placebo solution intravenously for 30 min in every 3 weeks. Oxaliplatin 130 mg/m2 (body surface area) solution intravenously for 2 hours once-daily, followed by 20 days off.

  Tegafur-gimeracil-oteracil potassium combination drug 40 - 60 mg bid or Capecitabine 1000 mg/ m2 (body surface area) bid orally in 14 days, followed by 7 days off.

  Each drug will be continued until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.

  Interventions:

  • Drug: Oxaliplatin
  • Drug: Tegafur- Gimeracil-Oteracil potassium
  • Drug: Capecitabine
  • Drug: Placebo

• Publications *: Boku N, Ryu MH, Kato K, Chung HC, Minashi K, Lee KW, Cho H, Kang WK, Komatsu Y, Tsuda M, Yamaguchi K, Hara H, Fumita S, Azuma M, Chen LT, Kang YK. Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4). Ann Oncol. 2019 Feb 1;30(2):250-258. doi: 10.1093/annonc/mdy540.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: February 28, 2017): 680
• Original Estimated Enrollment (submitted: April 18, 2016): 268
• Estimated Study Completion Date: March 2022
• Actual Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with unresectable advanced or recurrent gastric cancer (including esophagogastric junction cancer) that has not been treated with the first-line therapy with systemic antitumor agents for advanced or recurrent gastric cancer (including esophagogastric junction cancer)
• Have measurable lesions as defined in RECIST Guideline Version 1.1
• ECOG PS score 0 or 1
• Have a life expectancy of at least 3 months

Exclusion Criteria:

• Have multiple cancers
• Have a current or past history of severe hypersensitivity to any other antibody products
• Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment
• Patients with active, known or suspected autoimmune disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan, Korea, Republic of, Taiwan

Administrative Information

• NCT Number: NCT02746796
• Other Study ID Numbers: ONO-4538-37
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• URL: https://www.ono.co.jp/eng/rd/policy.html

• Responsible Party: Ono Pharmaceutical Co. Ltd
• Study Sponsor: Ono Pharmaceutical Co. Ltd
• Collaborators: Not Provided

Investigators

• Study Director: Mitsunobu Tanimoto; Ono Pharmaceutical Co. Ltd

• PRS Account: Ono Pharmaceutical Co. Ltd
• Verification Date: October 2020