Imatinib and Pembrolizumab combination therapy for advanced KIT-mutant melanoma: a phase I/II trial (IMPAKT trial)

JRCT ID: jRCTs031190202

Registered date:05/02/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced KIT-mutant melanoma
• Date of first enrollment: 23/12/2020
• Target sample size: 22
• Study type: Interventional

Intervention(s)

P1: 3+3 design to evaluate safety and tolerability and identify maximum tolerated dose/administered.
Level 1: Imatinib 200 mg/day, QD (day at 1-21), pembrolizumab 200 mg/body, Q3W (day at 1)
Level 2: Imatinib 400 mg/day, QD (day at 1-21), Pembrolizumab 200 mg/body, Q3W (day at 1)
P2: Eligible patients receive the dose determined in phase 1 cohort. An Simon's minimax two-stage design is employed to test the null hypothesis of a 5% RR vs 30% alternative (1-sided alpha 0.05, power 80%, >= 1/7 RR to continue to total of 3>=14). *
* Evaluate based on the results from RP2D cohort in P1 and P2 stage1

Outcome(s)

• Primary Outcome: Response rate after administration of four dosing cycle
• Secondary Outcome: Progression-free survival, overall survival, best overall response, adverse event type/ frequency/ severity (CTCAE 5.0).

Key inclusion & exclusion criteria

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

Include criteria

1) Age 20 years or older on day of signing consent.
2) Has histologically or cytologically confirmed as malignant melanoma.
3) Has unresectable or metastatic KIT-mutant melanoma
4) Patients which is not controlled by standard therapy (immune checkpoint inhibitor, molecular target drug etc.)
5) Has been untreated for advanced or metastatic disease by imatinib.
6) Has resolution of toxic effects of the most recent prior therapy.
7) Has the presence of at least one measurable lesion by image per RECIST 1.1.
8) Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
9) Life expectancy of greater than 90 days
10) Has no-central nerve system (CNS) metastasis or asymptomatic CNS metastasis.
11) Agreed to use an adequate method of contraception within the project duration of the study, starting with the visit through 120 days after the last dose of the study treatment.
12) Has laboratory parameters within Protocol-defined range. The screening laboratory tests below must be < 14 days before treatment initiation.
-White blood cell count >= 2,000/mm3 , absolute neutrophil count >= 1,500/mm3
-Platelets >= 100,000/mm3
-Hemoglobin >= 9.0g/dl
-Aspartate aminotransferase (AST), alanine aminotransferase (ALT) <= 150 IU/L
-Bilirubin <= 2.0mg/dl
-Serum creatinine <= 1.5mg/dl
13) Provide written informed consent for the study.

Exclude criteria

1) Seropositivity to HBsAg or HCVAb.
2) Has known history of HIV.
3) Has active infection, clinically significant cardiac disease, including unstable angina and arrhythmia, interstitial pneumonia, psychiatric disorder.
4) Has grade 3 or worse superior vena cava syndrome, pericardial effusion, pleural effusion, ascites.
5) Has uncontrolled disease that might confound the results of the study, or is not best interest of the subject to participate, in the opinion of the treating investigator.
6) Has double cancer (completely resected basal cell carcinoma, carcinoma in situ, or superficial bladder cancer, or patients with other cancers that do not show recurrence for more than 3 years before obtaining consent)

Related Information

• Primary Sponsor: Funakoshi Takeru
• Source(s) of Monetary Support: OHARA Pharmaceutical Co.,Ltd.,MSD Co., Ltd.,Daiichi Sankyo Company, Limited,Japan Agency for Medical Research and Development
• Secondary ID(s): NCT04546074