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

Sponsor
Centre Leon Berard
Study ID
NCT03714958
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • HDM201 — DRUG
    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.
  • Trametinib — DRUG
    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.

Study Details

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.

Key Dates

Start date
Dec 20, 2018
Status verified
Sep 2023
Primary completion
Sep 12, 2023
Completion
Sep 12, 2023

Study Design

Enrollment
12 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: combination HDM201 - Trametinib
    * HDM201: Therapeutic class HDM2 inhibitor, given Per Os every D1 and D8 over a 28 day cycle. Four dose-levels possible in dose escalation part: 40 mg, 80mg, 100 mg, 120mg. * Trametinib: Therapeutic class Protein kinase inhibitor of MEK1 and MEK2 activation and kinase activity. Administrated daily, countinous dosing , twodose-level possible in dose escalation: 1.5 mg and 2mg

Primary Outcome Measure

Part1: Dose Maximum Tolerated [ Time Frame: During the first 2 cycles of tratment (1 cycle = 28 days) ]

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