Nivolumab for malig nant mesothelioma from non-pleural orig in : A multicenter sing le-arm phase II study

JRCT ID: jRCT2051200062

Registered date:05/10/2020

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Malignant Mesothelioma
• Date of first enrollment: 20/10/2020
• Target sample size: 23
• Study type: Interventional

Intervention(s)

Multicenter, open-label, uncontrolled study
unblinded, uncontrolled, single group, group comparison

Outcome(s)

• Primary Outcome: Tumor shrinkage (response rate) (Central Decision, R EC IS T Guideline 1.1)

Secondary Outcome

efficacy
1.Tumor shrinkage (response rate) (Physician Judgment by Medical Institution, RECIST Guidelines Version 1.1)
2.Tumor shrinkage (disease control rate) (Central Decision, RECIST Guidelines Version 1.1)
3.overall survival time
4.Progression-Free survival (median, RECIST Guidelines Version 1.1)
5.Duration of response (Central Decision, RECIST Guidelines Version 1.1)
6.Time to response (Central Decision, RECIST Guidelines Version 1.1)
7.Best overall effect (Central Decision, RECIST Guidelines Version 1.1)
8.Rate of change in the sum of tumor diameters of target lesions (Central Decision, RECIST Guidelines Version 1.1)
safety
1.adverse event
2.Laboratory tests (Hematologic, biochemical, qualitative urine, immunologic, and hormonal tests)
3.Vital signs (Systolic/diastolic BP, pulse rate, percutaneous oxygen saturation (S p O2), temperature), weight
4.12-lead electrocardiogram
5.chest X-ray
6.ECOG Performance Status

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Patients over 20 years old
2. Patients diagnosed with malignant mesothelioma (remove the pleura) by histological diagnosis.
3. Patients who are determined by the investigator or sub investigator to have at least one measurable lesion as defined in RECIST Version 1.1 by CT or MRI on imaging within 14 days prior to enrollment.However, for malignant mesothelioma other than malignant peritoneal mesothelioma such as pericardium and tunica vaginalis, the presence or absence of measurable lesions does not matter.
4. Any history of treatment for malignant mesothelioma (remove the pleura) is warranted. Excluding patients previously treated with drugs specified in the exclusion criteria (15).
5. Patients with an ECOG performance status of 0 or 1
6. Patients expected to survive over 90 days
7. Patients with percutaneous oxygen saturation over 94%, as measured by pulse oximeter at rest, without supplemental O2 within 7 days before enrollment. However, if the baseline measurement is not included within 7 days before the initial dose of the investigational product, it should be reconfirmed that the baseline measurement is met.
8. Patients whose latest laboratory values obtained within 7 days of enrollment meet the following criteria. However, if the laboratory test at the time of registration is not included within 7 days before the first administration of the investigational product, it should be reconfirmed that the laboratory test before the first administration of the investigational product meets the following criteria. In all cases, laboratory test values are those for which granulocyte colony-stimulating factor (G-CSF formulation) or blood transfusion was not received within 14 days before the test date. White blood cell count > 2,000/m3 and neutrophil count > 15000/m3 Platelet count > = 100,000/m3 Hb > = 9.0 g/d L AST (GOT) and ALT (GPT) are not more than 3.0 times the upper limit of the facility reference value. Total bilirubin not more than 2.0 times the upper limit of institutional standard value Serum creatinine not more than 1.5 times the upper limit of the reference value at the institution Or creatinine clearance (Cockcroft estimates) > 45 m L/m in.
9. Patients who have been fully informed of the details of the study by the investigator or sub investigator using a written informed consent form and who voluntarily agree to participate in the study

Exclude criteria

1. Patients with a complication or history of severe hypersensitivity reactions to other drugs including antibody preparations
2. Patients with a history of concomitant autoimmune disease or chronic or recurrent autoimmune disease. However, patients with skin disease that does not require systemic therapy (Vitiligo, psoriasis, and alopecia), disease that does not appear to recur in the absence of external triggers, or associated hypothyroidism that can be managed with hormone replacement therapy can be enrolled.
3. Patients with multiple cancers (Patients with a history of completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, carcinoma in mucosa or superficial bladder cancer, or other cancers that have not recurred for more than 5 years can be enrolled)
4. Patients with brain or meningeal metastases. However, patients who are asymptomatic and do not require treatment may be enrolled. Patients whose disease is stable after completion of treatment for the lesion at least 28 days prior to entry into the study and who do not require continued use of systemic adrenocortical hormones during the 14 days prior to entry into the study can be enrolled.
5. Patients with a complication or history of interstitial lung disease or pulmonary fibrosis diagnosed by diagnostic imaging or clinical findings. For radiation pneumonitis,however, patients with confirmed fibrosis stabilization and no risk of recurrence can be enrolled.
6. Patients with coexisting diverticulitis or symptomatic gastrointestinal ulcer disease
7. Patients with accumulation of pericardial or ascites requiring drainage more frequently than once every 2 weeks
8. Patients with pericardial effusion or ascites requiring drainage more frequently than once every 2 weeks
9. Patients with pain associated with uncontrollable tumors
10. Patients with a history of transient ischemic attack, cerebrovascular attack, thrombosis, or thromboembolism (Pulmonary embolism or deep vein thrombosis) within 18 days before enrollment
11. Patients with the following uncontrolled or significant cardiovascular diseases
i.Myocardial infarction within 180 days before enrollment
ii.Uncontrolled angina within 180 days before enrollment
iii.New York Heart Association (NYHA) class III or IV congestive heart failure
iv.Uncontrolled hypertension (Systolic blood pressure of 150 mmHg or more or diastolic blood pressure of 90 mmHg or more lasting for 24 hours or more, etc.) despite appropriate treatment
v.uncontrollable arrhythmia
12. Patients receiving anticoagulant therapy (Exclude antiplatelet therapy, including low-dose aspirin)
(Except in patients who have been controlled with anticoagulation)
13. Patients with uncontrolled diabetes
14. Patients with systemic infections requiring treatment
15. HIV-1 antibody test, HIV-2 antibody test, HTLV-1 antibody test,
Patients with positive HBs antigen test or HCV antibody test.
Patients with negative HBsAg test but positive HBsAb test or HBcAb test and HBV-DNA quantitation above detection sensitivity
16. ONO-4538 (MDX-1106 or BMS-936558),
Anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, anti-CD137 antibody, anti-CTLA-4 antibody, or other antibody therapies intended to control T cells Patients with a history of prior drug therapy
17. Surgery with general, local, or surface anesthesia within 14 days before enrollment patient receiving therapy
18. Patients who underwent pleural, peritoneal, or pericardial adhesions within 28 days before enrollment
19. Patients who received palliative radiation therapy within 14 days before enrollment
20. Patients who received radiopharmaceuticals (Excluding the use of radiopharmaceuticals for inspection and diagnosis) within 56 days before enrollment
21. Patients who received other unapproved drugs (Including drugs administered in clinical studies, unapproved combination drugs, and new dosage forms) within 28 days (90 days for antibody preparations) before enrollment
22. Patients who received systemic corticosteroids (Excluding temporary use for the purpose of tests, prophylactic administration for allergic reactions, or reduction of edema associated with radiation therapy) or immunosuppressants in excess of 10mg/day of prednisolone equivalent within 28 days before enrollment
23. Patients who received live or attenuated vaccines within 28 days before registration
24. Pregnant women Patients who are judged to lack the ability to consent due to complications such as dementia
25. Patients who are considered to be unable to consent due to complications such as dementia
26. Other patients judged by the investigator or subinvestigator to be unsuitable for the study.

Related Information

• Primary Sponsor: Kijima Takashi
• Source(s) of Monetary Support: ONO PHARMACEUTICAL CO., LTD.