A Multicenter, Randomized, Open-label Study in Patients with esophageal Cancer refractory or intolerant to Combination Therapy with Fluoropyrimidine and Platinum-based Drugs

Phase 1

Conditions: Esophageal Cancer
MedDRA version: 21.0Level: LLTClassification code 10015362Term: Esophageal cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-003339-36-DK

Lead Sponsor: Ono Pharmaceutical Co., Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 390

Inclusion Criteria

1.Sex: Male or female
2.Age (at the time of informed consent): 20 years and older
3.Patients with esophageal cancer and whose major lesion in the esophagus (if already resected, the major lesion in the esophagus prior to resection) satisfies the following criteria. For patients with multiple lesions, the deepest invasion by clinical diagnosis should be considered the major lesion. Lesions other than the major lesion should be considered as secondary lesions. Esophageal cancer in this study is defined as a cancer that has primarily developed from the esophagus.
•Patients with a major lesion located in the cervical esophagus or thoracic esophagus (upper, middle, or lower thoracic region; including the esophagogastric junction)
•Patients whose histological type of major lesion was pathologically proven squamous cell carcinoma or adenosquamous cell carcinoma (pathological diagnosis of secondary lesions in the esophagus is not mandatory)
4.Patients who are refractory or intolerant to combination therapy with fluoropyrimidine and platinum-based drugs for esophageal cancer, have previously received 1 treatment regimen, and are not indicated for a radical resection. The definition of refractory should be defined as follows; and a therapy applicable to the following should be counted as 1 regimen.
•Patients whose PD or recurrence was confirmed by imaging during their initial chemotherapy (including chemoradiation) or within 8 weeks after the last dose of chemotherapy will be assessed as refractory.”
•Patients who underwent a radical resection (R0 resection confirmed) in conjunction with chemotherapy including neo-adjuvant/adjuvant therapy and chemoradiation (including patients who underwent chemoradiation followed by salvage surgery) whose recurrence was confirmed by imaging within 24 weeks after the last dose of chemotherapy will be determined as refractory.”
•If a CR (=2 consecutive CRs confirmed by imaging after an interval of =4 weeks) was assessed as a result of the initial chemotherapy (including chemoradiation), patients whose recurrence was confirmed by imaging during the initial chemotherapy (including chemoradiation) or within 24 weeks after the last dose of chemotherapy will be determined as refractory.”
5.Patients who have at least 1 measurable or non-measurable lesion per the RECIST Guideline Ver. 1.1 as confirmed by imaging within 28 days before randomization. The following requirements should also be satisfied:
•The primary esophageal cancer should be deemed to be non-measurable lesion.
•If patients only have lesions that were previously treated with radiation, the lesion should be limited to one with confirmed aggravation by imaging after radiation.
•If patients have pericardial or pleural effusion or ascites only, the lesion should be limited to one with cytologically confirmed malignancy.
6.ECOG Performance Status Score 0 or 1
7.Patients with a life expectancy of at least 3 months
8.Patients must provide tumor tissue (stored tissue or tissue from the last biopsy) for analysis of PD-L1 expression. For patients who are unable to undergo another biopsy, stored tissue can be used for analysis. Tissue specimens must contain at least 100 evaluable tumor cells and must be available at the time of informed consent.
9.Patients whose latest laboratory data meet the below criteria within 7 days before randomization. If the date of the laboratory tests at the time of randomization is not within 7 days b

Exclusion Criteria

1.significant malnutrition. Patients will be excluded if they are receiving intravenous hyperalimentation, or require continuous infusion therapy with hospitalization. Patients whose nutrition has been well controlled for =28 days prior to randomization may be enrolled.
2.apparent tumor invasion on organs located adjacent to the esophageal disease (e.g., the aorta or respiratory tract). Patients will be excluded if they are receiving stent therapy in esophagus or respiratory tract.
3.multiple primary cancers
4.residual adverse effects of prior therapy or effects of surgery that would affect the safety evaluation of the investigational product in the opinion of the investigator or subinvestigator
5.current or past history of severe hypersensitivity to any other antibody products
6.concurrent autoimmune disease or history of chronic or recurrent autoimmune disease
7.current or past history of interstitial lung disease or pulmonary fibrosis diagnosed based on imaging or clinical findings. Patients with radiation pneumonitis may be randomized if the radiation pneumonitis has been confirmed as stable (beyond acute phase) without any concerns about recurrence.
8.concurrent diverticulitis or symptomatic gastrointestinal ulcerative disease
9. any metastasis in the brain or meninx that is symptomatic or requires treatment. Patients may be randomized if the metastasis is asymptomatic and requires no treatment.
10.pericardial fluid, pleural effusion, or ascites requiring treatment
11.uncontrollable, tumor-related pain
12.transient ischemic attack, cerebrovascular accident, thrombosis, or thromboembolism (pulmonary arterial embolism or deep vein thrombosis) within 180 days before randomization
13.history of uncontrollable or significant cardiovascular disease meeting any of the following criteria:
·Myocardial infarction within 180 days before randomization
·Uncontrollable angina pectoris within 180 days before randomization
·New York Heart Association (NYHA) Class III or IV congestive heart failure
·Uncontrollable hypertension despite appropriate treatment (e.g., systolic blood pressure =150 mmHg or diastolic blood pressure =90 mmHg lasting 24 hours or more)
·Arrhythmia requiring treatment
14.anticoagulant therapy for a disease. Patients receiving antiplatelet therapy including low-dose aspirin may be enrolled.
15.uncontrollable diabetes mellitus
16.systemic infections requiring treatment
17.= Grade 2 peripheral neuropathy
18.systemic corticosteroids (except for temporary use, e.g., for examination or prophylaxis of allergic reactions) or immunosuppressants within 28 days before randomization
19.antineoplastic drugs (e.g., chemotherapy agents, molecular-targeted therapy agents, or immunotherapy agents) within 28 days before randomization
20.surgical adhesion of the pleura or pericardium within 28 days before randomization
21.surgery under general anesthesia within 28 days before randomization
22.surgery involving local or topical anesthesia within 14 days before randomization
23.radiotherapy within 28 days before randomization, or radiotherapy to bone metastases within 14 days before randomization
24.any radiopharmaceuticals (except for examination or diagnostic use of radiopharmaceuticals) within 56 days before randomization
25. positive test result for any of the following: HIV-1 antibody, HIV-2 antibody, HTLV-1 antibody, HBs antigen, or HCV antibody
26.Patients with a negative HBs an

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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