Phase II study of the safety and efficacy of TM5614 in combination with Paclitaxel for cutaneous angiosarcoma

JRCT ID: jRCT2021230016

Registered date:15/07/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Cutaneous Hemangiosarcoma
• Date of first enrollment: 25/10/2023
• Target sample size: 16
• Study type: Interventional

Intervention(s)

(TM5614)
TM5614 should be taken orally after breakfast for up to 28 weeks, starting with two tablets (120 mg) once daily. However, the dose may be taken after lunch on the starting day of administration and on the day of visit to the hospital. The patients can skip(suspend) medication by PI or Sub-I's decision.
(1) Dose escalation of TM5614
After 4 weeks of treatment, the investigator will confirm whether the dose of the study drug can be increased or not. If the investigator determines that the dose can be increased, the dose will be increased to 180 mg. However, if the dose could not be increased at the 4-week point due to the timing of the subject's visit or other reasons, the dose can be increased after the 4-week point.
(2) Dose reduction of TM5614
If the investigator judges that it is difficult to continue the dosage of 180 mg due to the occurrence of an adverse event caused by the investigational drug after the dosage has been increased to 180 mg, the investigator may reduce the dosage to 120 mg.

(Paclitaxel)
The dosage and administration of paclitaxel at the time of enrollment or at the time of the last dose should be maintained during the study period. However, the dose may be reduced by the investigator's decision.

Outcome(s)

• Primary Outcome: Objective response rate at 28 weeks (Central Review Evaluation)

Secondary Outcome

-Response rate at 28 weeks of treatment ( PI/SI's assessment)
-Response rate at 8 and 16 weeks of treatment (Central Review Evaluation and PI/SI's assessment)
-Objective response rate (PI/SI's assessment)
-Disease control rate (PI/SI's assessment)
-Progression-free survival
-Overall survival

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Patients who are 18 years old over (at the time of consent)
(2) Patients who have obtained written consent from the patient (or a surrogate) to participate in this study
(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 with recurrent or unresectable disease who have received prior chemotherapy with paclitaxel for the target disease and who continue to receive paclitaxel after paclitaxel failure.
*Definition of paclitaxel failure: Patients with a PD response whose condition worsens during paclitaxel maintenance therapy and who exhibit any of the following findings
-Tumor imaging (e.g., CT) changes do not meet the definition of PR with an increase of more than 10% in tumor diameter.
-Newly arising lesions.
-The appearance of a new mural nodule or an increase in the diameter of an existing mural nodule.
(5) Patients confirmed to have one or both of the following criteria within 14 days before enrollment in this trial:
-Patients who have at least one measurable lesions as defined in RECIST Guideline Version 1.1 in diagnostic imaging.
Patients with at least one superficial lesion with a maximum diameter of 10 mm or more that can be measured by color photography.
(6) ECOG performance status 0-1.
(7) Life expectancy >=90 days
(8) Women of childbearing potential (including patients who are not menstruating for medical reasons such as chemical menopause) who agree to use double contraception from the time of consent until at least 5 months after the last dose of study drug. In addition, patients who have agreed not to breastfeed for at least 5 months after the last administration of the treatment drug from the time of consent.
(9) For male patients, patients who have agreed to use dual contraception from the time of study drug administration for at least 7 months after the last dose of study drug.
(10) Patients whose most recent laboratory tests performed within 7 days prior to enrollment in the study meet the following criteria. The laboratory values must not have received granulocyte colony stimulating factor (G-CSF) administration or blood transfusion within 14 days prior to the test.
- White blood cell count greater than 2,000/mm3
- Neutrophil count greater than or equal to 1,500/mm3
- Platelet count greater than or equal to 100,000/mm3
- Hemoglobin is 9.0 g/dL or higher.
- AST and ALT less than 3 times the upper limit of the reference value of the medical institution (however, if the patient has liver metastasis, AST and ALT less than 5 times the upper limit of the reference value of the medical institution)

Exclude criteria

(1) Patients with concomitant or pre-existing severe hypersensitivity reactions to taxane anticancer agents
(2) Patients with residual adverse effects from previous therapy or surgical therapy that the investigator (subinvestigator) determines will affect the safety evaluation of the investigational drug.
(3) Patients with multiple cancers. (completely resected basal cell carcinoma, carcinoma in situ, intramucosal cancer or superficial bladder cancer, or patients with other cancers that have not recurred for more than 5 years prior to consent are enrolled to enable).
(4) Patients with central nervous system metastases. However, patients who are asymptomatic and do not require treatment can be registered.
(5) Patients with interstitial lung disease, pulmonary fibrosis, or radiation pneumonitis. However, patients with radiation pneumonitis who are confirmed to be stabilized by fibrosis and have no concern of relapse may be enrolled.
(6) Patients with diverticulitis or symptomatological gastrointestinal ulcer disease.
(7) Patients with pericardial fluid, pleural effusion or ascites that require continuous treatment.
(8) Patients whose tumor-related pain cannot be stably controlled.
(9) Patients with a history of transient ischemic or cerebrovascular attack within 180 days prior to enrollment in this study
(10)Patients with a history of thrombosis or thromboembolism (pulmonary artery embolism or deep vein thrombosis). However, patients who have passed 90 days or more and are not concerned about relapse can be registered.
(11) Patients participating in other clinical trials within 30 days prior to enrollment in this study.
(12) Patients with the following cardiovascular diseases:
-Patients with a history of myocardial infarction 6 months before registration.
-Patients with symptomatic arrhythmia requiring treatment.
(13) Patients who received radiation therapy within 28 days prior to enrollment in this study. However, irradiation for the purpose of mitigation and irradiation 15 days before registration is permitted.
(14) Patients who test positive for HIV antibodies, HBs antigen, or HCV antibodies. However, patients with a positive HBs antigen test but HBV-DNA quantification below the detection limit or a positive HCV antibody test but no active hepatitis C can be enrolled.
(15) Patients with bleeding tendency
(16) Patients with uncontrollable bleeding
(17) Patients with hemoptysis
(18) Patients who are pregnant, lactating or may be pregnant
(19) Other patients who are not eligible for this clinical trial by the investigator (or Sub-Investigator).

Related Information

• Primary Sponsor: Fujimura Taku
• Source(s) of Monetary Support: Renascience Inc.