Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

355 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-17

Study Completion Date

2027-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Patients meeting the inclusion criteria will be randomized 1:1 into Cohort A (n ≈ 177) or Cohort BC (n ≈ 177). Cohort A is the control: patients receive combination chemotherapy with FOLFOX plus anti-EGFR therapy (panitumumab or cetuximab) based on RAS/BRAF wild-type data, according to clinical guidelines.

The BC cohort begins FOLFOX chemotherapy and simultaneously undergoes extensive molecular genetic profiling. Further, the BC cohort, depending on the profile, is divided into cohort B - patients without changes in alternative oncogenes, and cohort C - with changes in alternative oncogenes. The expected cohort ratio is 3:1 (\~120 and \~40 patients). Cohort B begins to receive anti-EGFR therapy in addition to chemotherapy, and the potentially resistant cohort C continues to receive chemotherapy alone or begins to receive bevacizumab if there are no contraindications.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Safety and Efficacy of Folfox6 + Cetuximab Versus Folfiri +Cetuximab in Patients With Metastatic Colorectal Cancer

NCT00286130

Metastatic Colorectal Cancer

COMPLETED PHASE2

Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

NCT02928224

BRAF V600E-mutant Metastatic Colorectal Cancer

COMPLETED PHASE3

ObservationaL Study on the Qol of RAS Wild-type mCRC Patients Receiving Anti-EGFR MAbs + FOLFOX or FOLFIRI as 1st Line

NCT02624895

Metastatic Colorectal Cancer

COMPLETED

Study of Cetuximab, Oxaliplatin, 5-FU/LV Versus Oxaliplatin, 5-FU/LV in Patients With Previously Treated Metastatic, EGFR-Positive Colorectal Cancer

NCT00061815

Colorectal Cancer

COMPLETED PHASE3

FOLFOX Chemotherapy Regimen (5-FU, Leucovorin, Oxaliplatin) in Metastatic Colorectal Cancer

NCT00501410

Colorectal Cancer

COMPLETED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

In total, the study plans to include 355 patients diagnosed with unresectable metastatic colorectal cancer with a left-sided localization of the primary tumor, who have not previously received systemic therapy for metastatic disease, have wild-type KRAS/NRAS/BRAF, or have wild-type KRAS/NRAS with unknown BRAF status in no contraindications to targeted therapy (cetuximab/panitumumab/bevacizumab).

Patients meeting the inclusion criteria will be randomized 1:1 into Cohort A (n ≈ 177) or Cohort BC (n ≈ 177). Cohort A is the control: patients receive combination chemotherapy with FOLFOX plus anti-EGFR therapy (panitumumab or cetuximab) based on RAS/BRAF wild-type data, according to clinical guidelines. Next, this cohort, after completion of the protocol, undergoes extended profiling, according to the results of which it is divided into cohorts A1 and A2. Cohort A1 includes patients without changes in alternative oncogenes (N ≈ 120), cohort A2 includes patients with changes (N ≈ 40).

The BC cohort begins FOLFOX chemotherapy and simultaneously undergoes extensive molecular genetic profiling. Further, the BC cohort, depending on the profile, is divided into cohort B - patients without changes in alternative oncogenes, and cohort C - with changes in alternative oncogenes. The expected cohort ratio is 3:1 (\~120 and \~40 patients). Cohort B begins to receive anti-EGFR therapy in addition to chemotherapy, and the potentially resistant cohort C continues to receive chemotherapy alone or begins to receive bevacizumab if there are no contraindications.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Colorectal Neoplasms Chemotherapy Effect Molecular Sequence Variation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

randomize and compare contol and experimental groups

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

A

All patients will recieve chemotherapy FOLFOX (oxaliplatin 85 mg/m2 + folinic acid 400 mg/m2 + FU 400 mg/m2 bolus and FU 2400 mg/m2 46-hour insusion q2w) + anti-EGFR monoclonal antibody (cetuximab 500 mg/m2 q2w or panitumumab 6 mg/kg q2w) until disease progression or unacceptable toxicity. It is permited to withdraw oxaliplatin after 8 cycles.

Group Type ACTIVE_COMPARATOR

Cetuximab

Intervention Type DRUG

FOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de Gramont+cetuximab/panitumumab is allowed after 8 cycles

BC

All patients will recieve chemotherapy FOLFOX (oxaliplatin 85 mg/m2 + folinic acid 400 mg/m2 + FU 400 mg/m2 bolus and FU 2400mg/m2 46-hour insusion q2w). Monoclonal antibody will be added to chemotherapy after 1-2 cycles based on molecular profile results: anti-EGFR (cetuximab 500 mg/m2 q2w or panitumumab 6 mg/kg q2w) for hyperselected wild type tumors or bevacizumab 5 mg/m2 q2w for mutant profile.

Patients will recieve therapy until disease progression or unacceptable toxicity. It is permited to withdraw oxaliplatin after 8 cycles.

Group Type EXPERIMENTAL

Cetuximab

Intervention Type DRUG

FOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de Gramont+cetuximab/panitumumab is allowed after 8 cycles

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Cetuximab

FOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de Gramont+cetuximab/panitumumab is allowed after 8 cycles

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

panitumumab

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Informed consent signed before commencing any procedures related to the clinical trial.
2. Age ≥18 years.
3. ECOG status 0-2.
4. Life expectancy greater than 12 weeks as assessed by the investigator.
5. Verified diagnosis of colorectal adenocarcinoma (C18.5, C19, C20).
6. Metastatic unresectable form of the disease that has not previously received any systemic therapy for the metastatic process (previous neo-/adjuvant therapy completed at least 6 months before the detection of metastases is allowed).
7. Left-sided localization of the primary tumor (from the splenic flexure of the colon inclusive).
8. Verified wild type KRAS, NRAS determined from tumor tissue.
9. Satisfactory function of hematopoiesis and internal organs:

* absolute number of neutrophils ≥ 1.5×10 9 /l;
* platelets ≥ 100×10 9 /l;
* hemoglobin ≥ 90 g/l.
* creatinine clearance above 50 ml/min;
* total bilirubin \<1.5 X the upper limit of normal;
* ALT or AST \>5 X the upper limit of normal in the presence of liver metastases or \>2.5 X the upper limit of normal in the absence of liver metastases.
10. Availability of a sufficient amount of tumor material for molecular genetic research. Tumor material must be collected no more than 24 months before inclusion in the study.

Exclusion Criteria

1. Previous systemic therapy for metastatic disease.
2. Presence of KRAS/NRAS/V600E mutations (except for unknown BRAF status).
3. Uncertain KRAS/NRAS status
4. The presence of any other malignant tumor, with the exception of radically treated basal cell carcinoma, cervical cancer in situ, currently or within 5 years before inclusion in the study. Pregnant and lactating women, as well as planning pregnancy during the period of therapy in a clinical trial and 6 months after the end of therapy.
5. HIV infection, active hepatitis B, active hepatitis C.
6. Complicated primary tumor, requiring urgent surgical intervention. After it is eliminated, the patient can participate in the study.
7. The presence of a disease or condition that, in the opinion of the investigator, prevents the patient from participating in the study.
8. Impossibility of organizing central venous access.

Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No