Study of ONO-4538 in Gastric Cancer

NCT02746796 | Completed Phase 2 DMC

• 1 other identifier: ONO-4538-37
• Study Type: interventional
• Target: 680
• Locations: 3 countries
• Sites: 130

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• Progression-free survival (central assessment by IRRC) (only Part 2)

  Up to study completion (estimated time frame: 48 months)

• Overall survival (only Part 2)

  Up to study completion (estimated time frame: 54 months)

Secondary Outcomes (9)

• Objective response rate (only Part 2)

  Up to study completion (estimated time frame: 54 months)

• Progression-free survival (assessment by the site investigator)(only Part 2)

  Up to study completion (estimated time frame: 54 months)

• Duration of response (only Part 2)

  Up to study completion (estimated time frame: 54 months)

• Disease control rate (only Part 2)

  Up to study completion (estimated time frame: 54 months)

• Time to response (only Part 2)

  Up to study completion (estimated time frame: 54 months)

Study Arms (4)

ONO-4538 + SOX Therapy Cohort (Part 1)

EXPERIMENTAL

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.

Drug: ONO-4538; Drug: Oxaliplatin; Drug: Tegafur- Gimeracil-Oteracil potassium

ONO-4538 + CapeOX Therapy Cohort (Part 1)

EXPERIMENTAL

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.

Drug: ONO-4538; Drug: Oxaliplatin; Drug: Capecitabine

ONO-4538 + chemotherapy group (Part 2)

EXPERIMENTAL

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.

Drug: ONO-4538; Drug: Oxaliplatin; Drug: Tegafur- Gimeracil-Oteracil potassium; Drug: Capecitabine

Placebo + Chemotherapy group (Part 2)

PLACEBO COMPARATOR

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.

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

Interventions

ONO-4538 DRUG

ONO-4538 + CapeOX Therapy Cohort (Part 1); ONO-4538 + SOX Therapy Cohort (Part 1); ONO-4538 + chemotherapy group (Part 2)

Oxaliplatin DRUG

ONO-4538 + CapeOX Therapy Cohort (Part 1); ONO-4538 + SOX Therapy Cohort (Part 1); ONO-4538 + chemotherapy group (Part 2); Placebo + Chemotherapy group (Part 2)

Tegafur- Gimeracil-Oteracil potassium DRUG

ONO-4538 + SOX Therapy Cohort (Part 1); ONO-4538 + chemotherapy group (Part 2); Placebo + Chemotherapy group (Part 2)

Capecitabine DRUG

ONO-4538 + CapeOX Therapy Cohort (Part 1); ONO-4538 + chemotherapy group (Part 2); Placebo + Chemotherapy group (Part 2)

Placebo DRUG

Placebo + Chemotherapy group (Part 2)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ono Pharmaceutical Co. Ltd: lead

Study Sites (130)

Aichi Clinical Site

Nagoya, Aichi-ken, Japan

Location

Aomori Clinical Site

Hirosaki, Aomori, Japan

Location

Aomori Clinical Site

Misawa, Aomori, Japan

Location

Chiba Clinical Site

Funabashi, Chiba, Japan

Location

Chiba Clinical Site

Kamogawa, Chiba, Japan

Location

Chiba Clinical Site

Kashiwa, Chiba, Japan

Location

Ehime Clinical Site1

Matsuyama, Ehime, Japan

Location

Ehime Clinical Site2

Matsuyama, Ehime, Japan

Location

Fukuoka Clinical Site

Iizuka, Fukuoka, Japan

Location

Fukuoka Clinical Site1

Kitakyushu, Fukuoka, Japan

Location

Fukuoka Clinical Site2

Kitakyushu, Fukuoka, Japan

Location

Fukuoka Clinical Site

Kurume, Fukuoka, Japan

Location

Gifu Clinical Site

Gifu, Gifu, Japan

Location

Gifu Clinical Site

Ōgaki, Gifu, Japan

Location

Gumma Clinical Site

Maebashi, Gunma, Japan

Location

Gunma Clinical Site

Ōta, Gunma, Japan

Location

Gumma Clinical Site

Takasaki, Gunma, Japan

Location

Hiroshima Clinical Site

Kure, Hiroshima, Japan

Location

Hokkaido Clinical Site

Hakodate, Hokkaido, Japan

Location

Hokkaido Clinical Site1

Sapporo, Hokkaido, Japan

Location

Hokkaido Clinical Site2

Sapporo, Hokkaido, Japan

Location

Hokkaido Clinical Site3

Sapporo, Hokkaido, Japan

Location

Hokkaido Clinical Site4

Sapporo, Hokkaido, Japan

Location

Hyogo Clinical Site

Akashi, Hyōgo, Japan

Location

Hyogo Clinical Site

Amagasaki, Hyōgo, Japan

Location

Hyogo Clinical Site

Kobe, Hyōgo, Japan

Location

Hyogo Clinical Site

Nishinomiya, Hyōgo, Japan

Location

Ibaraki Clinical Site

Higashiibaraki-gun, Ibaraki, Japan

Location

Ibaraki Clinical Site

Tsuchiura-shi, Ibaraki, Japan

Location

Ishikawa Clinical Site1

Kanazawa, Ishikawa-ken, Japan

Location

Ishikawa Clinical Site2

Kanazawa, Ishikawa-ken, Japan

Location

Iwate Clinical Site

Morioka, Iwate, Japan

Location

Kagawa Clinical Site

Kita-gun, Kagawa-ken, Japan

Location

Kanagawa Clinical Site

Isehara, Kanagawa, Japan

Location

Kanagawa Clinical Site

Kamakura, Kanagawa, Japan

Location

Kanagawa Clinical Site

Sagamihara, Kanagawa, Japan

Location

Kanagawa Clinical Site1

Yokohama, Kanagawa, Japan

Location

Kanagawa Clinical Site2

Yokohama, Kanagawa, Japan

Location

Kanagawa Clinical Site3

Yokohama, Kanagawa, Japan

Location

Miyagi Clinical Site

Natori-shi, Miyagi, Japan

Location

Miyagi Clinical Site

Ōsaki, Miyagi, Japan

Location

Miyagi Clinical Site

Sendai, Miyagi, Japan

Location

Nagano Clinical Site

Saku, Nagano, Japan

Location

Nara Clinical Site

Ikoma, Nara, Japan

Location

Nara Clinical Site

Kashihara-shi, Nara, Japan

Location

Okayama Clinical Site

Kurashiki, Okayama-ken, Japan

Location

Osaka Clinical Site

Izumi, Osaka, Japan

Location

Osaka Clinical Site

Sakai, Osaka, Japan

Location

Osaka Clinical Site

Sayama, Osaka, Japan

Location

Osaka Clinical Site

Suita, Osaka, Japan

Location

Osaka Clinical Site

Takatsuki, Osaka, Japan

Location

Osaka Clinical Site

Toyonaka, Osaka, Japan

Location

Saitama Clinical Site

Hidaka, Saitama, Japan

Location

Saitama Clinical Site

Kitaadachi-gun, Saitama, Japan

Location

Shizuoka Clinical Site

Hamamatsu, Shizuoka, Japan

Location

Tochigi Clinical Site

Shimotsuke, Tochigi, Japan

Location

Tochigi Clinical Site

Utsunomiya, Tochigi, Japan

Location

Tokyo Clinical Site

Bunkyo-ku, Tokyo, Japan

Location

Tokyo Clinical Site

Chuo-ku, Tokyo, Japan

Location

Tokyo Clinical Site

Fuchū, Tokyo, Japan

Location

Tokyo Clinical Site

Koto-ku, Tokyo, Japan

Location

Tokyo Clinical Site

Minato-ku, Tokyo, Japan

Location

Tokyo Clinical Site

Shinagawa-ku, Tokyo, Japan

Location

Tokyo Clinical Site1

Shinjuku-ku, Tokyo, Japan

Location

Tokyo Clinical Site2

Shinjuku-ku, Tokyo, Japan

Location

Tokyo Clinical Site

Tachikawa, Tokyo, Japan

Location

Tottori Clinical Site

Yonago, Tottori, Japan

Location

Yamagata Clinical Site

Sakata, Yamagata, Japan

Location

Akita Clinical Site

Akita, Japan

Location

Chiba Clinical Site1

Chiba, Japan

Location

Chiba Clinical Site2

Chiba, Japan

Location

Fukui Clinical Site

Fukui, Japan

Location

Fukuoka Clinical Site1

Fukuoka, Japan

Location

Fukuoka Clinical Site2

Fukuoka, Japan

Location

Fukuoka Clinical Site3

Fukuoka, Japan

Location

Fukuoka Clinical Site4

Fukuoka, Japan

Location

Fukushima Clinical Site

Fukushima, Japan

Location

Hiroshima Clinical Site1

Hiroshima, Japan

Location

Hiroshima Clinical Site2

Hiroshima, Japan

Location

Hiroshima Clinical Site3

Hiroshima, Japan

Location

Kumamoto Clinical Site1

Kumamoto, Japan

Location

Kumamoto Clinical Site2

Kumamoto, Japan

Location

Kumamoto Clinical Site3

Kumamoto, Japan

Location

Kyoto Clinical Site1

Kyoto, Japan

Location

Kyoto Clinical Site2

Kyoto, Japan

Location

Kyoto Clinical Site3

Kyoto, Japan

Location

Niigata Clinical Site

Niigata, Japan

Location

Okayama Clinical Site

Okayama, Japan

Location

Osaka Clinical Site1

Osaka, Japan

Location

Osaka Clinical Site2

Osaka, Japan

Location

Osaka Clinical Site3

Osaka, Japan

Location

Osaka Clinical Site4

Osaka, Japan

Location

Shizuoka Clinical Site

Shizuoka, Japan

Location

Tokushima Clinical Site

Tokushima, Japan

Location

Toyama Clinical Site

Toyama, Japan

Location

Wakayama Clinical Site

Wakayama, Japan

Location

Yamagata Clinical Site

Yamagata, Japan

Location

Gyeongnam Clinical Site

Gyeongnam, Gyeongsangnam-do, South Korea

Location

Busan Clinical Site

Busan, South Korea

Location

Daegu Clinical Site 1

Daegu, South Korea

Location

Daegu Clinical Site 2

Daegu, South Korea

Location

Daejeon Clinical Site

Daejeon, South Korea

Location

Gyeonggi-Do Clinical Site1

Gyeonggi-do, South Korea

Location

Gyeonggi-Do Clinical Site2

Gyeonggi-do, South Korea

Location

Gyeonggi-Do Clinical Site3

Gyeonggi-do, South Korea

Location

Gyeonggi-Do Clinical Site4

Gyeonggi-do, South Korea

Location

Gyeonggi-Do Clinical Site5

Gyeonggi-do, South Korea

Location

Incheon Clinical Site

Incheon, South Korea

Location

Jeollabuk-Do Clinical Site

Jeollabuk-Do, South Korea

Location

Jeollanam-do Clinical Site

Jeollanam-do, South Korea

Location

Seoul Clinical Site 1

Seoul, South Korea

Location

Seoul Clinical Site 2

Seoul, South Korea

Location

Seoul Clinical Site 3

Seoul, South Korea

Location

Seoul Clinical Site 4

Seoul, South Korea

Location

Seoul Clinical Site 5

Seoul, South Korea

Location

Seoul Clinical Site 6

Seoul, South Korea

Location

Seoul Clinical Site7

Seoul, South Korea

Location

Seoul Clinical Site8

Seoul, South Korea

Location

Seoul Clinical Site9

Seoul, South Korea

Location

Ulsan Clinical Site

Ulsan, South Korea

Location

Kaohsiung Clinical Site1

Kaohsiung City, Taiwan

Location

Kaohsiung Clinical Site2

Kaohsiung City, Taiwan

Location

New Taipei Clinical Site 1

New Taipei City, Taiwan

Location

Taichung Clinical Site 1

Taichung, Taiwan

Location

Taichung Clinical Site2

Taichung, Taiwan

Location

Tainan Clinical Site1

Tainan, Taiwan

Location

Tainan Clinical Site2

Tainan, Taiwan

Location

Taipei Clinical Site1

Taipei, Taiwan

Location

Taipei Clinical Site2

Taipei, Taiwan

Location

Taoyuan Clinical Site

Taoyuan District, Taiwan

Location

Related Publications (3)

• Boku N, Omori T, Shitara K, Sakuramoto S, Yamaguchi K, Kato K, Kadowaki S, Tsuji K, Ryu MH, Oh DY, Oh SC, Rha SY, Lee KW, Chung IJ, Sym SJ, Chen LT, Chen JS, Bai LY, Nakada T, Hagihara S, Makino R, Nishiyama E, Kang YK. Nivolumab plus chemotherapy in patients with HER2-negative, previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: 3-year follow-up of the ATTRACTION-4 randomized, double-blind, placebo-controlled, phase 3 trial. Gastric Cancer. 2024 Nov;27(6):1287-1301. doi: 10.1007/s10120-024-01535-0. Epub 2024 Aug 20.

  PMID: 39162872 DERIVED

• Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):234-247. doi: 10.1016/S1470-2045(21)00692-6. Epub 2022 Jan 11.

  PMID: 35030335 DERIVED

• 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.

  PMID: 30566590 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Nivolumab; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Mitsunobu Tanimoto

  Ono Pharmaceutical Co. Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2016
• First Posted: April 21, 2016
• Study Start: March 1, 2016
• Primary Completion: January 1, 2020
• Study Completion: November 17, 2022
• Last Updated: May 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (23); TW (10); JP (97)