Esophageal CancerPhase 3NCT02569242

Study of Nivolumab in Unresectable Advanced or Recurrent Esophageal Cancer

A Phase 3 study testing Nivolumab and Docetaxel/Paclitaxel in people with Esophageal Cancer, run by Ono Pharmaceutical Co., Ltd. at 89 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Esophageal Cancer
What is being tested?: Nivolumab and Docetaxel/Paclitaxel
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 419 participants
Where: 89 sitesin 8 countries
Study dates: 14 Dec 2015to 23 Oct 2020
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

89 sites in 8 countries.

Country

City, postcode or hospital

89 sites in 8 countries

Japan46 sites

Hyogo Clinical Site
Akashi, Hyōgo, 673-0021
Akita Clinical Site
Akita, 010-8543
Tokyo Clinical Site
Bunkyo-ku, Tokyo, 113-0021
Chiba Clinical Site
Chiba, 260-0801
Chiba Clinical Site
Chiba, 260-8677
Tokyo Clinical Site
Chuo-ku, Tokyo, 104-0045
Tokyo Clinical Site
Chuo-ku, Tokyo, 104-8560
Fukuoka Clinical Site
Fukuoka, 812-8582
Fukushima Clinical Site
Fukushima, 960-1295
Saitama Clinical Site
Hidaka, Saitama, 350-1298
Aomori Clinical Site
Hirosaki, Aomori, 036-8563
Hiroshima Clinical Site
Hiroshima, 734-8551
Kanagawa Clinical Site
Isehara, Kanagawa, 259-1193
Kagoshima Clinical Site
Kagoshima, 890-8520
Chiba Clinical Site
Kashiwa, Chiba, 277-8577
Kanagawa Clinical Site
Kawasaki, Kanagawa, 216-0015
Saitama Clinical Site
Kita-Adachi County, Saitama, 362-0806
Hyogo Clinical Site
Kobe, Hyōgo, 650-0047
Tokyo Clinical Site
Koto-ku, Tokyo, 135-8550
Kumamoto Clinical Site
Kumamoto, 860-8556
Kyoto Clinical Site
Kyoto, 602-8566
Kyoto Clinical Site
Kyoto, 606-8507
Ehime Clinical Site
Matsuyama, Ehime, 791-0288
Tokyo Clinical Site
Meguro-ku, Tokyo, 152-8902
Tokyo Clinical Site
Minato-ku, Tokyo, 105-8470
Aichi Clinical Site
Nagoya, Aichi-ken, 464-8681
Aichi Clinical Site
Nagoya, Aichi-ken, 466-8560
Niigata Clinical Site
Nigatake, Niigata, 951-8520
Niigata Clinical Site
Niigata, 951-8566
Osaka Clinical Site
Osaka, 537-8511
Nagano Clinical Site
Saku, Nagano, 385-0051
Hokkaido Clinical Site
Sapporo, Hokkaido, 003-0027
Hokkaido Clinical Site
Sapporo, Hokkaido, 060-8648
Osaka Clinical Site
Sayama, Osaka, 589-8511
Miyagi Clinical Site
Sendai, Miyagi, 980-8574
Tochigi Clinical Site
Shimotsuke, Tochigi, 329-0431
Tokyo Clinical Site
Shinagawa-ku, Tokyo, 142-8666
Tokyo Clinical Site
Shinjuku-ku, Tokyo, 160-8582
Tokyo Clinical Site
Shinjuku-ku, Tokyo, 162-8666
Shizuoka Clinical Site
Shizuoka, 420-8527
Osaka Clinical Site
Suita, Osaka, 565-0871
Shizuoka Clinical Site
Suntou County, Shizuoka, 411-8777
Osaka Clinical Site
Takatsuki, Osaka, 569-0801
Mie Clinical Site
Tsu, Mie-ken, 514-8507
Kanagawa Clinical Site
Yokohama, Kanagawa, 236-0004
Kanagawa Clinical Site
Yokohama, Kanagawa, 241-8515

Other trials in Japan

South Korea12 sites

Busan Clinical Site
Busan, 49241
Daegu Clinical Site
Daegu, 41404
Daegu Clinical Site
Daegu, 41931
Daejeon Clinical Site
Daejeon, 35015
Gyeonggi-do Clinical Site
Gyeonggi-do, 13620
Hwasun-Gun Clinical Site
Hwasun-Gun, 58128
Seoul Clinical Site
Seoul, 03080
Seoul Clinical Site
Seoul, 03722
Seoul Clinical Site
Seoul, 05505
Seoul Clinical Site
Seoul, 06351
Seoul Clinical Site
Seoul, 06591
Ulsan Clinical Site
Ulsan, 44033

Other trials in South Korea

Taiwan11 sites

Changhua Clinical Site
Changhua, 500
Chiayi Clinical Site
Chiayi City, 61363
Kaohsiung Clinical Site
Kaohsiung City, 807
Kaohsiung Clinical Site
Kaohsiung City, 82445
Kaohsiung Clinical Site
Kaohsiung City, 83301
Keelung Clinical Site
Keelung, 20445
Taichung Clinical Site
Taichung, 40447
Tainan Clinical Site
Tainan, 704
Taipei Clinical Site
Taipei, 10048
Taipei Clinical Site
Taipei, 11217
Taoyuan Clinical Site
Taoyuan, 333

Other trials in Taiwan

United States7 sites

Massachusetts General Hospital
Boston, Massachusetts, 02114
Duke Cancer Institute
Durham, North Carolina, 27710
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
The University Of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Vanderbilt-Ingram Cancer Ctr
Nashville, Tennessee, 37232
Orlando Health, Inc
Orlando, Florida, 32806
Georgetown University Med Ctr
Washington D.C., District of Columbia, 20007

Other trials in United States

Germany7 sites

RWTH Aachen University
Aachen, 52057
Charite Campus Virchow Klinikum
Berlin, D-13353
University Hospital Heidelberg
Heidelberg, 69120
Universitatsklinikum Jena, Innere Medizin II
Jena, 07747
MVZ Mitte
Leipzig, 04103
University Of Mainz Medical Center
Mainz, 55131
Klinikum reechts der Isar, Technical University Munchen
Munich, 81675

Other trials in Germany

Italy3 sites

HPG23
Bergamo, 24127
Fondazione Irccs Istituto Nazionale Tumori
Milan, 20133
Irccs Istituto Oncologico Veneto Iov
Padova, 35128

Other trials in Italy

United Kingdom2 sites

Velindre Cancer Centre
Cardiff, Cardiganshire, CF142TL
The Beatson West Of Scotland Cancer Centre
Glasgow, Lanarkshire, G12 0YN

Other trials in United Kingdom

Denmark1 site

Odense University Hospital
Odense C, 5000

Other trials in Denmark

About this study

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

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.

Conditions: Esophageal Cancer
Being tested: Nivolumab, Docetaxel/Paclitaxel
Medical subject headings: Esophageal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NivolumabDrug
Docetaxel/PaclitaxelDrug

Study groups in NCT02569242
Study group	Role	What they receive
Nivolumab Arm	Experimental	Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends Receives: Drug: Nivolumab
Active Comparator Arm （Docetaxel/Paclitaxel）	Active comparator	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 Receives: Drug: Docetaxel/Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Survival
Measured: ("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.

Secondary outcomes (2)

Progression-free Survival
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)."
Measured: ("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.
Duration of Response
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)."
Measured: ("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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Dec 201523 Oct 2020

First posted6 Oct 2015 (estimated)
Study start14 Dec 2015
Primary completion23 Oct 2020
Study completion23 Oct 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Esophageal CancerStudies of the same condition, open and under way.
More trials run by Ono Pharmaceutical Co., Ltd.The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 419 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02569242
Sponsor's protocol ID: ONO-4538-24/CA209-473
Status last verified: Jan 2022
First submitted: 30 Sep 2015
Last updated: 6 Jul 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes

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.
PubMed 31582355

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Esophageal Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02569242
Acronym / sponsor ID: ONO-4538-24/CA209-473
Conditions: Esophageal Cancer
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 419 participants (actual)
Lead sponsor: Ono Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
Collaborators: Bristol-Myers Squibb
Study start: 14 Dec 2015 (actual)
Primary completion: 23 Oct 2020 (actual)
Study completion: 23 Oct 2020 (actual)
First posted: 6 Oct 2015 (estimated)
Results: Posted 14 Jan 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

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

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Nivolumab	Drug	Nivolumab Arm
Docetaxel/Paclitaxel	Drug	Active Comparator Arm （Docetaxel/Paclitaxel）

Primary outcome

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.

2 secondary outcomes

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.
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.

Results and safety

Results posted to the registry on 14 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Nivolumab Arm	210	209
Active Comparator Arm （Docetaxel/Paclitaxel）	209	208

Primary outcome: 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.. Median (95% Confidence Interval). Unit: months

Measure	Nivolumab Arm n = 210	Active Comparator Arm （Docetaxel/Paclitaxel） n = 209
Value	10.9 (9.2 to 13.3)	8.4 (7.2 to 9.9)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Monitoring for any AEs will be continued until 28 days after the end of the treatment phase. In subjects who, at the time of initiation of the follow-up investigation, have any AE for which a causal relationship to the investigational product cannot be ruled out or which led to discontinuation, investigation of the AE will be continued until the event is judged not to require further follow-up. SAEs are to be collected during the treatment period and for 100 days following the last dose.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Nivolumab Arm	68 of 209 (32.5%)	185 of 209 (88.5%)	7 of 209
Active Comparator Arm （Docetaxel/Paclitaxel）	77 of 208 (37%)	204 of 208 (98.1%)	5 of 208

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31582355Kato 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.
Individual participant dataSharing planned: Yes

Related trials for Esophageal Cancer

RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingObservational study
Multicenter Prospective Cohort on Esophageal Endoscopic Submucosal Dissection
Superficial Esophageal Cancer, Oesophageal Adenocarcinoma
Recruiting
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RecruitingPhase 2
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RecruitingPhase 1
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ono Pharmaceutical Co., Ltd. Ono Pharmaceutical Co., Ltd. study director

Ono Pharmaceutical Co., Ltd.

89 sites in 8 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nivolumab and Docetaxel/Paclitaxel in people with Esophageal Cancer, run by Ono Pharmaceutical Co., Ltd. at 89 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 89 sites in Japan, South Korea, Taiwan, United States, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02569242, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2022.