A Multicenter, Open-label, Uncontrolled Phase II study of ONO-4538 [immune-checkpoint inhibitor] for cutaneous angiosarcoma

JRCT ID: jRCT2031200020

Registered date:22/04/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Advanced or recurrent cutaneous hemangiosarcoma
• Date of first enrollment: 07/05/2020
• Target sample size: 23
• Study type: Interventional
• Intervention(s): Four hundred and forty-eight mg of ONO-4538 is administered intravenously for 30 minutes in every 4 weeks interval. Four weeks are defined as 1 cycle. According to RECIST Guideline Version 1.1, administration will be continued for up to 2 years until the investigator or sub-investigator decided as meeting ONO-4538 treatment termination criteria or individual subject discontinuation criteria or discontinuation criteria. Continue to administer for up to 2 years until determined. Changes of the ONO-4538 dose (480 mg) are not allowed.

Outcome(s)

• Primary Outcome: Objective response rate (Central Review Evaluation)

Secondary Outcome

1. Objective response (Investigational Review Evaluation)
2. Disease control rate (Central Review Result)
3. Overall survival
4. Progression-free survival (Central Review Result)
5. Response period (Central Review Result)
6. Time to response (Central Review Result)
7. Best overall response (Central Review Result)
8. Rate of change in sum of tumor diameters of target lesion
9. Maximum change rate in the sum of tumor diameters of the target lesion

Key inclusion & exclusion criteria

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

Include criteria

1. Sex: Both
2. Age (at the time of consent): 20age old over
3. Patients who have been confirmed by histology or cytology to be cutaneous angiosarcoma and cannot be cured by surgery and radiation therapy
4. Patients who have received prior chemotherapy with paclitaxel and/or docetaxel, which is the standard treatment for the target disease
5. Patients confirmed to have one or both of the following criteria within 14 days before enrollment in this trial:
-Patients who have one or more measurable lesions as defined in RECIST Guideline Version 1.1 in diagnostic imaging (Patients who received radiation therapy for measurable lesions have progressed on imaging diagnosis after radiation therapy)
-Patients with one or more superficial lesions with a maximum diameter of 10 mm or more, whose size can be measured by color photography, and whose boundaries with normal skin are clearly defined
6. Patients with ECOG Performance Status 0-1
7. Patients expected to survive more than 90 days
8. For women of childbearing potential (including patients who have no menstruation due to medical reasons such as chemical menopause), patients who have agreed to double contraception from obtaining the consent to at least 5 months of the last dose of study drug. Patients who have agreed not to breastfeed for at least 5 months after the last dose of study drug after obtaining consent
9. Patients whose latest clinical laboratory values be perfomed within 7 days prior to enrollment in this trial satisfy 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 drug, conduct the test again within 7 days before the first administration of the investigational drug, and reconfirm that the following criteria are met. In each case, the clinical laboratory value has not been administered or transfused with granulocyte colony stimulating factor (G-CSF preparation) within 14 days before the test.
-White blood cell count of 2,000 / mm3 or more and neutrophil count of 1000 / mm3 or more
-Platelet count is 100,000 / mm3 or more
-Hemoglobin 8.0g / dL or more
-AST (GOT) and ALT (GPT) are equal to or less than 3.0 times the facility standard upper limit
-Total bilirubin is 2.0 times or less of the facility standard upper limit
-Serum creatinine is 1.5 mg / dL or less or creatinine clearance (actual value or estimated value by Cockcroft / Gault formula) is 45 mL / min or more
10. Patients who have been fully explained by the Investigator or sub-investigator about the contents of this study using consent documents and explanatory documents, and who freely agreed to participate in this study in writing

Exclude criteria

1.Patients with a current or past history of hypersensitivity to other antibody preparations
2.Patients determined by the investigator or sub-investigator to affect the safety evaluation of the investigational drug due to adverse effects of previous treatment or the effects of surgical treatment
3.Patients with a current history of autoimmune disease or past history of chronic or recurrent autoimmune disease. However, patients with hypothyroidism that can be treated by hormone replacement therapy or skin diseases (white spots, psoriasis, alopecia, etc.) that do not require oral administration, infusion, or immunosuppressants of hypothyroidism or corticosteroids therapy (equivalent to more than 10 mg / day of prednisolone) can be registered.
4.Patients with double cancer (completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, carcinoma in the mucosa or superficial bladder carcinoma, or no recurrence for more than 5 years) Patients with other cancers that are not allowed can be registered)
5.Patients with central nervous system metastases. However, patients who are asymptomatic and do not need treatment can be registered.
6. Patients with current or past history of interstitial lung disease, pulmonary fibrosis or radiation pneumonitis diagnosed by imaging or clinical findings. However, with regard to radiation pneumonitis, stabilization due to fibrosis has been confirmed, and patients with no fear of relapse can be registered.
7. Patients with diverticulitis or symptomatic gastrointestinal ulcer disease
8. Patients with pericardial effusion, pleural effusion, or ascites that require continuous treatment
9. Patients whose tumor-related pain cannot be controlled stably
10. Patients with past history of transient ischemic attack or cerebral vascular attack within 180 days before enrollment in this study
11. Patients with past history of thrombosis or thromboembolism (pulmonary embolism or deep vein thrombosis). However, patients who have passed 180 days or more and have no fear of relapse can be enrolled.
12. Patients with the following unmanageable or serious cardiovascular diseases
- Myocardial infarction within 180 days before enrollment in this trial
- Unmanageable angina within 180 days before enrollment in this trial
- New York Heart Association (NYHA) Cardiac Function Class I or II Congestive Heart Failure
- Uncontrollable hypertension despite appropriate treatment (eg, systolic blood pressure > 150 mmHg or diastolic blood pressure < 90 mmHg for >24 h)
- Uncontrolled arrhythmias

13. Patients with unmanageable diabetes
14. Patients with systemic infection requiring treatment
15. Patients who need transplant therapy or have a past history of transplant therapy (excluding autologous transplant)
16. Patients with past history of severe allergy
17. Patients who require treatment with systemic corticosteroids (equivalent to prednisolone greater than 10 mg / day) or other immunosuppressive drugs within 28 days before enrollment in this study. However, temporary use of corticosteroids for testing or prophylactic administration against allergic reactions is permitted.
18. Administration of other unapproved drugs within 28 days prior to enrollment in this trial (90 days for antibody products)
(Including patients who have received clinical studies, unapproved combination drugs, and new drug types)
19. Patients who have received any anti-neoplastic agents (such as chemotherapy, targeted therapy, hormonal therapy and immunotherapy) within 28 days before enrollment in this trial
20. Patients who underwent pleural or pericardial adhesions within 28 days prior to enrollment in this trial
21. Patients who underwent surgery with general anesthesia within 28 days before enrollment in this trial
22. Patients who underwent surgery with local or surface anesthesia (excluding biopsy) within 14 days prior to enrollment in this trial
23. Patients who received radiation therapy within 28 days before enrollment in this trial. However, in the case of irradiation for palliative treatment, it must not have been irradiated within 14 days before enrollment in this trial.
24. Patients who received live or attenuated vaccinations within 28 days prior to enrollment in this trial
25. Patients who have received radiopharmaceuticals (excluding the use of radiopharmaceuticals for testing and diagnosis) within 56 days prior to enrollment in this trial
26. Patients with past history of acquired immunodeficiency syndrome (AIDS). Or a patient who has a positive human immunodeficiency virus (HIV) test, HTLV-1 antibody test, HBs antigen test, or HCV antibody test (if the HCV antibody is positive in HCV antibody-positive patients, it is eligible). Patients who have a negative HBs antigen test but have a positive HBs antibody test or HBc antibody test and have HBV-DNA quantification higher than the detection sensitivity
27. Pregnant, nursing or possibly pregnant patients
28. Previous treatment history of anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 or other antibody or drug therapy for T cell control patients
29. Patients deemed to lack consent ability due to complications of dementia
30. Other patients judged by the Investigator or sub-investigator to be inappropriate for the study

Related Information

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