Neoplasms
Conditions
Keywords
metastatic colorectal cancer, BRAF V600E- mutated, first line, MSS, treatment
Brief summary
The purpose of this study is to evaluate the efficacy and toxicity of FOLFOX regimen with dabrafenib and cetuximab/panitumumab in the first line of therapy for the potential treatment of colorectal cancer that: has a metastatic, inoperable; has a mutation in the BRAF gene and MSS. Participants in this study will receive one of the following study treatments: These participants will receive FOLFOX regimen with dabrafenib and cetuximab or panitumumab in the first line of therapy This study is currently enrolling participants who will receive either FOLFOX regimen with dabrafenib and cetuximab or panitumumab in the first line of therapy. The study team will monitor how each participant responds to the study treatment for up to about 3 years.
Detailed description
The purpose of the study is to evaluate the efficacy and toxicity of first-line FOLFOX with dabrafenib and cetuximab or panitumumab in patients with previously untreated metastatic inoperable colorectal cancer who have MSS and BRAF mutation.
Interventions
DRUGmFOLFOX6 + dabrafenib and cetuximab or panitumumab in the first line of therapy
Dabrafenib 150 mg twice orally daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks or Panitumumab 6 mg/kg (60-minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks, Сalcium folinate 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks.
Sponsors
City Clinical Oncology Hospital No 1
Moscow City Oncology Hospital No. 62
The Loginov MCSC MHD
MMCC Kommunarka MHD
Blokhin's Russian Cancer Research Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
* Drug: Dabrafenib * Drug: Cetuximab * Drug: Рanitumumab * Drug: Oxaliplatin * Drug: Irinotecan * Drug: Leucovorin * Drug: 5-FU
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed colorectal adenocarcinoma that contains MSS and BRAF V600E mutation * Metastatic inoperable colorectal cancer * Adequate function of hematopoiesis and basic indicators of internal organs * Has measurable or evaluable disease according to Response Evaluation Criteria In Solid Tumors (RECIST v1.1). * Lacking antitumor systemic treatment for colorectal cancer. * Patients with progression after adjuvant chemotherapy may be included if progression is recorded no earlier than 12 months after the last course of chemotherapy. * The primary tumor is removed or asymptomatic. * Absence of grade 2 or higher neuropathy. * Absence of tumor MSI or dMMR. * ECOG PS 0-2
Exclusion criteria
* 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). * Presence of any other malignancy, except radically treated basal cell carcinoma, cervical cancer in situ, currently or within 5 years prior to enrolment. * Pregnant and breastfeeding women. * Male and female patients with preserved reproductive potential who refused to use adequate contraception throughout the study. * HIV-infected patients. * Patients with a life expectancy of less than 3 months. * The presence of a disease or condition that, in the opinion of the investigator, prevents the patient from participating in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | assessed at 8 and 16 weeks | From date of enrollment until the date of first documented objective response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | assessed up to 24 months | From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first |
| Time to objective response | assessed up to 12 months | Time from start of treatment to objective response to treatment |
| Overall survival | assessed up to 36 months | From the time of enrolment until the death from any cause |
Other
| Measure | Time frame | Description |
|---|---|---|
| Duration of response | assessed up to 12 months | Calculated from achieving objective response to progression or death from any cause |
| Frequency of dose reductions and drug withdrawals | through study completion, an average of 1 year | Proportion of patients with dose reductions and drug withdrawals in the total number of patients |
| Disease control rate | through study completion, an average of 1 year | Percentage of patients who achieved a complete response, partial response or disease stabilisation |
| Incidence of adverse events | through study completion, an average of 1 year | Proportion of patients with adverse events out of all patients (NCI CTCAE 5.0) |
| Incidence of adverse events grade 3-4 | through study completion, an average of 1 year | Proportion of patients with adverse events grade 3-4 out of all patients (NCI CTCAE 5.0) |
Countries
Russia
Contacts
Primary ContactMikhail Fedyanin MD
Backup ContactEvgenia Kuzmina MD
Outcome results
None listed