Dabrafenib and Trametinib in pediatric patients with refractory advanced Solid Tumors with BRAF V600 mutations

JRCT ID: jRCTs011220017

Registered date:01/09/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: 12 months to 15 year- old patients with unresectable or refractory solid cancer with BRAF V600
• Date of first enrollment: 18/05/2023
• Target sample size: 28
• Study type: Interventional

Intervention(s)

Dabrafenib capses are administered orally twice daily according to the package insert. Dabrafenib dispersible tablets are administered orally twice daily at doses based on body weight and age.
Trametinib tablets are administered orally once daily according to the package insert. Trametinib oral solution is administered orally once daily at a dose based on body weight.

Outcome(s)

• Primary Outcome: Confirmed response rate based on RECIST version 1.1 up to 24 weeks after initiation of treatment in the patients with measurable disease

Secondary Outcome

Confirmed response rate based on RECIST version 1.1 in the patients with measurable disease
Best percent change in the sum of diameters of measurable lesions evaluated according to RECIST version 1.1
Response rate based on RECIST version 1.1 for study subjects with measurable disease, replacing RANO based best overall response for the patients with primary brain tumors with measurable disease
Response rate based on RANO for the patients with primary brain tumors
In patients with histiocytosis, transition of clinical score for disease activity (DAS)
In patients with histiocytosis, response rate according to Histiocyte Society assessment guidelines.
Proportion of disease control, progression free survival, and overall survival, including patients with measurable disease and them without measurable disease
adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 12month old
• Age maximum: <= 15age old
• Gender: Both

Include criteria

1) 12 months to 15 years
2) Patients are diagnosed with pediatric solid cancer (including histiocytosis, not including colorectal cancer) by JCCG central review or Implementation facility
3) Patients are diagnosed with solid cancers with BRAF V600 by comprehensive genome profiling. In the patients with histiocytosis, BRAF V600E mutation was confirmed by JCCG central review
4) recurrent, unresectable or refractory solid cancer
5) PS :0 to 2
6) Patients do not receive chemotherapy or radiotherapy at the registration
7) more than 7 days since the completion of radiotherapy
8) meet the inspection value within 14 days of the registration.
9)Patient agree the study

Exclude criteria

1) having other cancers
2) having infections
3) having fever, over 38.0
4) during pregnancy
5) Patients administered immunosuppressive agents
6) Patients administered BRAF inhibitor or MEK inhibitor
7) Patients administered concomitant prohibited drugs
8) Patients received allogeneic hematopoietic stem cell transplantation within 3 months.
9) having daiabetes mellitus
10) having congestive heart failure within 3 months.
11) having cancers with RAS pathway activation or BRAF-KIAA1549 fusion
12) HIV antibody positive
13) A history of infection with HBV or HCV. However, patients negative for HBsAg, positive for HBsAb or HBcAb, with HBV-DNA below detection limits, may be eligible. Similarly, those positive HCV Ab, with HCV-RNA below detection limits, may also be eligible.
14) having retinal vein occlusion or central serous chorioretinal vein retinopathy
15) Responsible investigator or investigator considers ineligible

Related Information

• Primary Sponsor: Kinoshita Ichiro
• Source(s) of Monetary Support: crowdfunding