Study of Nivolumab in Unresectable Advanced or Recurrent Esophageal Cancer

• ClinicalTrials.gov Identifier: NCT02569242
• Recruitment Status: Completed
• First Posted: October 6, 2015
• Results First Posted: January 14, 2022
• Last Update Posted: July 6, 2022
• Sponsor: Ono Pharmaceutical Co. Ltd
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Ono Pharmaceutical Co. Ltd

Tracking Information

• First Submitted Date: September 30, 2015
• First Posted Date: October 6, 2015
• Results First Submitted Date: October 20, 2021
• Results First Posted Date: January 14, 2022
• Last Update Posted Date: July 6, 2022
• Actual Study Start Date: December 14, 2015
• Actual Primary Completion Date: October 23, 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 5, 2022): Overall Survival [ Time Frame: ("Date of death from any cause" - "Date of randomization" + 1) / 30.4375. For subjects lost to follow-up and subjects who are alive at the time of data cutoff date, data will be censored at the time the subject was last confirmed to be alive. ]
• Original Primary Outcome Measures (submitted: October 2, 2015): Overall survival [ Time Frame: Estimated time frame: 30 months ]

Current Secondary Outcome Measures (submitted: January 5, 2022)

• Progression-free Survival [ Time Frame: ("Earlier date on which either the overall response was assessed as PD or the subject died of any cause" - "Date of randomization" + 1) / 30.4375. ]
  Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of "Not Evaluable (NE)."
• Duration of Response [ Time Frame: ("Earlier date on which either the overall response was assessed as PD for the first time after confirmed response or the subject died of any cause" - "Date of first assessment of confirmed CR or PR" + 1) / 30.4375. ]
  Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of "Not Evaluable (NE)."

Original Secondary Outcome Measures (submitted: October 2, 2015)

• Progression-free survival [ Time Frame: Estimated time frame: 30 months ]
• Objective response rate [ Time Frame: Estimated time frame: 30 months ]
• Duration of response [ Time Frame: Estimated time frame: 30 months ]
• Safety will be analyzed through the incidence of adverse events, serious adverse events [ Time Frame: Continuously throughout study treatment and up to 28 days from last dose ]
• Safety will be analyzed through the incidence of laboratory abnormalities [ Time Frame: Continuously throughout study treatment and 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 Nivolumab in Unresectable Advanced or Recurrent Esophageal Cancer
• Official Title: ONO-4538 Phase III Study A Multicenter, Randomized, Open-label Study in Patients With Esophageal Cancer Refractory or Intolerant to Combination Therapy With Fluoropyrimidine and Platinum-based Drugs
• Brief Summary: The purpose of study is to evaluate the efficacy and safety of Nivolumab in unresectable advanced or recurrent esophageal cancer patients who have failed in standard chemotherapies.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Esophageal Cancer

Intervention

• Drug: Nivolumab
• Drug: Docetaxel/Paclitaxel

Study Arms

• Experimental: Nivolumab Arm
  Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
  Intervention: Drug: Nivolumab
• Active Comparator: Active Comparator Arm （Docetaxel/Paclitaxel）

  Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

  OR

  Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

  Intervention: Drug: Docetaxel/Paclitaxel

• Publications *: Kato K, Cho BC, Takahashi M, Okada M, Lin CY, Chin K, Kadowaki S, Ahn MJ, Hamamoto Y, Doki Y, Yen CC, Kubota Y, Kim SB, Hsu CH, Holtved E, Xynos I, Kodani M, Kitagawa Y. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019 Nov;20(11):1506-1517. doi: 10.1016/S1470-2045(19)30626-6. Epub 2019 Sep 30. Erratum In: Lancet Oncol. 2019 Nov;20(11):e613.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 6, 2021): 419
• Original Estimated Enrollment (submitted: October 2, 2015): 390
• Actual Study Completion Date: October 23, 2020
• Actual Primary Completion Date: October 23, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men & women ≥20 years of age
• Histologically confirmed unresectable advanced or recurrent esophageal cancer
• Refractory to or intolerant of standard therapy
• ECOG Performance Status score 0 or 1
• A life expectancy of at least 3 months

Exclusion Criteria:

• Current or past history of severe hypersensitivity to any other antibody products
• Patients with multiple primary cancers
• 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: Denmark, Germany, Italy, Japan, Korea, Republic of, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02569242
• Other Study ID Numbers: ONO-4538-24/CA209-473
• 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

• Current Responsible Party: Ono Pharmaceutical Co. Ltd
• Original Responsible Party: Same as current
• Current Study Sponsor: Ono Pharmaceutical Co. Ltd
• Original Study Sponsor: Same as current
• Collaborators: Bristol-Myers Squibb

Investigators

• Study Director: Ono Pharmaceutical Co., Ltd. Ono Pharmaceutical Co., Ltd.; Ono Pharmaceutical Co. Ltd

• PRS Account: Ono Pharmaceutical Co. Ltd
• Verification Date: January 2022