NCT03714958

Trametinib + HDM201 in CRC Patients With RAS/RAF Mutant and TP53 Wild-type Advanced/Metastatic Colorectal Cancer Mutant and TP53 Wild-type

A Single-center, Phase 1 Dose Escalation Study of Trametinib Combined With HDM201 in Patients With RAS/RAF Mutant and TP53 Wild-type Advanced/Metastatic Colorectal Cancer.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Recent preclinical studies suggest that combining MEK and MDM2 inhibition synergize to induce apoptosis in RAS/BRAF-mutant and TP53 wild-type CRC models. In vitro, in RKO cell lines (poorly differentiated colon carcinoma cell line resistant to single agent targeting MDM2 and MEK and BRAF inhibition), the MDM2 plus MEK inhibitor combination generated a synergistic increase in apoptotic index. In vivo, in mice harboring human RKO colon tumor xenografts the combination of MDM2 plus MEK inhibition elicited 93% decreases in tumor volume. This trial is to conduct a single-center, Phase 1 dose escalation study of trametinib combined with HDM201 (a HDM2 inhibitor) in patients with advanced/metastatic RAS/RAF mutant and TP53 wt CRC.

Detailed description

This trial is a Phase I dose escalation study aiming to evaluate the safety of a combined treatment associating HDM201 (escalating doses) with Trametinib (fixed dose). This study will utilize sequential and adaptive Bayesian design using the method of Time-to-event Continual Reassessment Method (CRM) to guide dose escalation and estimate the MTD.

Conditions

• Colorectal Cancer
• Advanced Cancer
• Metastatic Cancer

Interventions

Type	Name	Description
DRUG	HDM201	Treatment will be administered as long as patient experience clinical benefit in the opinion of the investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.
DRUG	Trametinib	Treatment will be administered as long as patient experience clinical benefit in the opinion of the investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

Timeline

• Start date: 2018-12-20
• Primary completion: 2023-09-12
• Completion: 2023-09-12
• First posted: 2018-10-22
• Last updated: 2023-09-13

Locations

1 site across 1 country: France