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

Phase 2Active Not RecruitingNCT06967155

Blokhin's Russian Cancer Research Center23 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasms

Interventions

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.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Objective Response Rate

From date of enrollment until the date of first documented progression

Time frame: assessed up to 12 months

Secondary Outcomes

Progression-free survival

From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first

Time frame: assessed up to 24 months

Time to objective response

Time from start of treatment to objective response to treatment

Time frame: assessed up to 6 months

Duration of response

Calculated from achieving objective response to progression or death from any cause

Time frame: assessed up to 12 months

Disease control rate

Time frame: 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

Time frame: assessed up to 36 months

Incidence of adverse events

Time frame: Proportion of patients with adverse events out of all patients (NCI CTCAE 5.0)

Incidence of adverse events grade 3-4

Time frame: Proportion of patients with adverse events grade 3-4 out of all patients (NCI CTCAE 5.0)

Reduction of dose reductions and drug withdrawals

Time frame: Proportion of patients with dose reductions and drug withdrawals in the total number of patients