NCT04423185

PLATFORM Study of Precision Medicine for Rare Tumors

Platform Study of Genotyping Guided Precision Medicine for Rare Tumors in China

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 770 (estimated)
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A Phase II, open label, non-randomized, multiple-arm, single-center clinical trial in patients with advanced rare solid tumors who failed to standard treatment.

Detailed description

Based on the fact that a high incidence rate (14.2%) of rare tumor (incidence rate \<2.5/100,000) as defined in this study according to the National Cancer Registry data from National Cancer Center of China, as well as the current status of lacking guidelines and consensus of rare tumor treatment. We proposed this study "A Phase II, open label, non-randomized, multiple-arm, single-center clinical trial in patients with advanced rare solid tumors who failed to standard treatment", aims to evaluate the safety and efficacy of targeted drugs of specific tumor-driven genes in patients with advanced rare solid tumors with corresponding actionable alterations, as well as the safety and efficacy of immune checkpoint (PD-1) inhibitors in patients with advanced rare solid tumors without actionable alterations. Patients with advanced rare tumors who failed to standardized treatment carrying actionable alterations as "EGFR mutation (exon 19 deletion mutation, L858R replacement mutation), ALK gene fusion, ROS-1 gene fusion, C-MET gene amplification or mutation (D1010 mutation, 14 exon mutation, y1003 mutation), BRAF mutation, CDKN2A mutation, BRCA1/2 mutation, HER-2 mutation, HER-2 over expression/amplification, C-KIT mutation", will enroll targeted therapy arms and be given corresponding targeted drugs (Dacomitinib, Crizotinib). And patients without targeted alterations mentioned above will enroll PD-1 inhibitor arm and to be treated with Sintilimab. After acquired resistance patients treated with olaparib and palbociclib will receive combination treatment with durvalumab. After acquired resistance patients treated with vemurafenib will receive combination treatment with atezolizumab. The statistics of current study adopts Simon's two-stage Minimax design: In the first stage of clinical research, 12 subjects will be observed. If the number of CR + PR is less than 1, the trial will be terminated, otherwise, the group will continue to expand to 16 subjects. Therefore, in the first stage, there are 12\*5/(1-10%)=54 patients of targeted treatment group and 126 patients in the immunotherapy group, 180 patients totally in the first stage. If they all enter the second stage, the final target treatment group is 16\*5/(1-10%) = 72 patients and the immunotherapy group which has 168 patients which brings to a total of 240 patients. The sample size of the study shall be adjusted according to the interim analysis. Primary Endpoint of this study is objective response rate (ORR) in immunotherapy group and targeted therapy group assessed by Blinded Independent Central Review (BICR) and investigator. Secondary Endpoints are Progression-Free Survival (PFS) in the targeted treatment group assessed by Blinded Independent Central Review and investigator; PFS (RECIST 1.1) and iPFS (iRECIST) in the single drug immunotherapy group assessed by Blinded Independent Central Review and investigator; Duration of Response (DoR) in the targeted therapy and single immunotherapy groups assessed by the investigator; Durable Clinical Benefit (DCB) in the single drug immunotherapy group; Incidence of Adverse Events (AE) in subjects ect.

Conditions

• Rare Tumor

Interventions

Type	Name	Description
DRUG	Almonertinib 110 MG	Patients with advanced rare tumors who failed to standardized treatment carrying EGFR mutations will be administrated with Almonertinib.
DRUG	Dacomitinib 45 MG	Patients with advanced rare tumors who failed to standardized treatment carrying EGFR mutations will be administrated with Dacomitinib.
DRUG	Alectinib 150 MG	Patients with advanced rare tumors who failed to standardized treatment carrying ALK fusion will be administrated with Alectinib.
DRUG	Crizotinib 250 MG	Patients with advanced rare tumors who failed to standardized treatment carrying ALK fusion, ROS-1 fusion, C-MET amplification, C-MET mutation will be administrated with Crizotinib.
DRUG	Pyrotinib 160/80 MG	Patients with advanced rare tumors who failed to standardized treatment carrying HER-2 mutation or HER-2 over expression/amplification will be administrated with Pyrotinib.
DRUG	Imatinib 400 MG	Patients with advanced rare tumors who failed to standardized treatment carrying CKIT mutation will be administrated with Imatinib.
DRUG	Niraparib 200/300 MG	Patients with advanced rare tumors who failed to standardized treatment carrying BRCA1/2 mutation will be administrated with Olaparib.
DRUG	Palbociclib 125mg	Patients with advanced rare tumors who failed to standardized treatment carrying CDKN2A mutation will be administrated with palbociclib.
DRUG	Vemurafenib 240 MG	Patients with advanced rare tumors who failed to standardized treatment carrying BRAF mutation will be administrated with Vemurafenib.
DRUG	Sintilimab 100MG	Patients with advanced rare tumors who failed to standardized treatment carrying no targeted alterations will be administrated with Sintilimab.
DRUG	Atezolizumab 1680 MG	Patients with BRAF mutation treated with vemurafenib, after acquired resistance, will combine vemurafenib with atezolizumab.

Timeline

• Start date: 2020-08-15
• Primary completion: 2026-07-01
• Completion: 2028-07-01
• First posted: 2020-06-09
• Last updated: 2025-02-11

Locations

1 site across 1 country: China