Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer (CRC01)

January 25, 2024 updated by: Pokataev Ilya, City Clinical Oncology Hospital No 1

Predictive Value of Other Oncogene Mutations for Anti-EGFR Monoclonal Antibodies Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer: Multicenter Randomized Phase III Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

355

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Ilya Pokataev, phD
  • Phone Number: 2007 +74955369406
  • Email: pokia@mail.ru

Study Contact Backup

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 108814
        • Recruiting
        • Moscow Multidiciplinary Clinical Center Kommunarka
        • Contact:
      • Moscow, Russian Federation, 115478
        • Recruiting
        • N.N Blokhin Cancer Reserch Center
        • Contact:
      • Reutov, Russian Federation, 143964
        • Recruiting
        • Reutov Clinical hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: Cetuximab
FOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de Gramont+cetuximab/panitumumab is allowed after 8 cycles
Other Names:
  • panitumumab
Experimental: 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.
Drug: Cetuximab
FOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de Gramont+cetuximab/panitumumab is allowed after 8 cycles
Other Names:
  • panitumumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression-free survival
Time Frame: through study completion, an average of 3 years
Intention to treat, Calculated from start of therapy to date of disease progression or death
through study completion, an average of 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
edverse events
Time Frame: through study completion, an average of 3 years
all AE based on CTC criteria v. 5
through study completion, an average of 3 years
overall survival
Time Frame: through study completion, an average of 3 years
Calculated from start of therapy to date of last contact or death
through study completion, an average of 3 years
progression-free survival based (per protocol)
Time Frame: through study completion, an average of 3 years
through study completion, an average of 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City Clinical Oncology Hospital No 1

Collaborators

Atlas Biomed
N.N. Blokhin National Medical Research Center of Oncology
Moscow MultidisciplinaryClinical Center Kommunarka

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 17, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

January 18, 2024

First Submitted That Met QC Criteria

January 18, 2024

First Posted (Actual)

January 26, 2024

Study Record Updates

Last Update Posted (Estimated)

January 29, 2024

Last Update Submitted That Met QC Criteria

January 25, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRC01
  • 2102-2/23 (Other Grant/Funding Number: Moscow Center for healthcare innovations)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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