A Study of Irinotecan With Dabrafenib Plus Trametinib and Anti-EGFR in the Second Line of Therapy in People With Metastatic Colorectal Cancer

Non-randomised, Multicentre, Prospective, Single-arm, Phase II Study of the Efficacy and Toxicity of a Combination of Irinotecan With Dabrafenib and Trametinib, Anti-EGFR in the Second Line of Treatment of Patients With Metastatic BRAF V600E- Mutated Colorectal Cancer.

The purpose of this study is to evaluate the efficacy and toxicity of irinotecan with dabrafenib, cetuximab/panitumumab in the second line of treatment for the potential treatment of colorectal cancer that: has a metastatic, inoperable; has a mutation in the BRAF gene.

Participants in this study will receive one of the following study treatments:

These participants will receive in the second line is irinotecan, dabrafenib + trametinib, cetuximab or panitumumab.

This trial is currently enrolling participants who will receive either irinotecan and dabrafenib plus cetuximab or panitumumab in the second line of therapy.

The study team will monitor how each participant responds to the study treatment for up to about 3 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasms
• Intervention / Treatment: Drug: • Drug: Dabrafenib • Drug: Trametinib • Drug: Cetuximab • Drug: Рanitumumab • Drug: Oxaliplatin • Drug: Irinotecan • Drug: Leucovorin • Drug: 5-FU

Detailed Description

The purpose of the study is to evaluate the efficacy and toxicity of irinotecan in combination with dabrafenib + trametinib and cetuximab or panitumumab in second-line treatment of patients with metastatic inoperable colorectal cancer who have a BRAF mutation.

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russia
  • Moscow
    • Moscow, Moscow, Russia, 115478
      • Blokhin's Russian Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Histologically confirmed metastatic inoperable colorectal adenocarcinoma
2. The tumour has a BRAF mutation
3. Adequate function of hematopoiesis and basic indicators of internal organs
4. Has measurable or evaluable disease according to Response Evaluation Criteria In Solid Tumors (RECIST v1.1).
5. Absence of grade 2 or higher toxicity from previous line of treatment.
6. It is possible to include patients with MSI or dMMR if they have received first-line immune checkpoint therapy.
7. ECOG PS 0-1

Exclusion Criteria:

1. Participants having more than 2 lines of treatment (a progression of disease within 12 months of the completion of adjuvant and/or perioperative chemotherapy with oxaliplatin and fluoropyrimidines is acceptable).
2. Presence of any other malignancy, except radically treated basal cell carcinoma, cervical cancer in situ, currently or within 5 years prior to enrolment.
3. Pregnant and breastfeeding women.
4. Male and female patients with preserved reproductive potential who refused to use adequate contraception throughout the study.
5. HIV-infected patients.
6. Patients with a life expectancy of less than 3 months.
7. The presence of a disease or condition that, in the opinion of the investigator, prevents the patient from participating in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Irinotecan + Dabrafenib + Trametinib and Cetuximab or Panitumumab in the second line of therapy; Irinotecan + Dabrafenib + Trametinib and Cetuximab or Panitumumab in the second line of therapy Dabrafenib 150 mg twice orally daily Trametinib 2 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks or Panitumumab 6 mg/kg (60-minute IV infusion) every two weeks Irinotecan 90 mg/m2 (90-minute IV infusion) weekly. Second-line treatment is administered until disease progression or intolerable toxicity. It may be possible to switch to a regimen of dabrafenib, trametinib, cetuximab or panitumumab if irinotecan is intolerable.

Drug: • Drug: Dabrafenib • Drug: Trametinib • Drug: Cetuximab • Drug: Рanitumumab • Drug: Oxaliplatin • Drug: Irinotecan • Drug: Leucovorin • Drug: 5-FU; Irinotecan + Dabrafenib + Trametinib and Cetuximab or Panitumumab in the second line of therapy Dabrafenib 150 mg twice orally daily Trametinib 2 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks or Panitumumab 6 mg/kg (60-minute IV infusion) every two weeks Irinotecan 90 mg/m2 (90-minute IV infusion) weekly. Second-line treatment is administered until disease progression or intolerable toxicity. It may be possible to switch to a regimen of dabrafenib, trametinib, cetuximab or panitumumab if irinotecan is intolerable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	From date of enrollment until the date of first documented progression	assessed up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first	assessed up to 24 months
Time to objective response	Time from start of treatment to objective response to treatment	assessed up to 6 months
Duration of response	Calculated from achieving objective response to progression or death from any cause	assessed up to 12 months
Disease control rate		Percentage of patients who achieved a complete response, partial response or disease stabilisation? through study completion, an average of 1 year
Overall survival	From the time of enrolment until the death from any cause	assessed up to 36 months
Incidence of adverse events		Proportion of patients with adverse events out of all patients (NCI CTCAE 5.0)
Incidence of adverse events grade 3-4		Proportion of patients with adverse events grade 3-4 out of all patients (NCI CTCAE 5.0)
Reduction of dose reductions and drug withdrawals		Proportion of patients with dose reductions and drug withdrawals in the total number of patients

Collaborators and Investigators

• Sponsor: Blokhin's Russian Cancer Research Center
• Collaborators: Moscow City Oncology Hospital No. 62; City Clinical Oncology Hospital No 1; The Loginov MCSC MHD; MMCC Kommunarka MHD
• Investigators: Principal Investigator: Mikhail Fedyanin MD, Blokhin's Russian Cancer Research Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): November 10, 2027
• Study Completion (Estimated): June 10, 2028

Study Registration Dates

• First Submitted: April 25, 2025
• First Submitted That Met QC Criteria: May 3, 2025
• First Posted (Actual): May 13, 2025

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 28, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: treatment; metastatic colorectal cancer; BRAF V600E- mutated
• Additional Relevant MeSH Terms: Neoplasms by Site; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplasms; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Micronutrients; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Protective Agents; Antidotes; Vitamin B Complex; Vitamins; Oxaliplatin; Irinotecan; Cetuximab; Trametinib; Dabrafenib; Leucovorin
• Other Study ID Numbers: 05202500302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No