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

NCT06226857 | Recruiting Phase 3

• 2 other identifiers: CRC012102-2/23
• Study Type: interventional
• Target: 355
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Colorectal Neoplasms; Chemotherapy Effect; Molecular Sequence Variation

Outcome Measures

Primary Outcomes (1)

• progression-free survival

  Intention to treat, Calculated from start of therapy to date of disease progression or death

  through study completion, an average of 3 years

Secondary Outcomes (3)

• edverse events

  through study completion, an average of 3 years

• overall survival

  through study completion, an average of 3 years

• progression-free survival based (per protocol)

  through study completion, an average of 3 years

Study Arms (2)

A

ACTIVE COMPARATOR

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

BC

EXPERIMENTAL

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

Interventions

Cetuximab DRUG

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

Also known as: panitumumab

A; BC

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent signed before commencing any procedures related to the clinical trial.
• Age ≥18 years.
• ECOG status 0-2.
• Life expectancy greater than 12 weeks as assessed by the investigator.
• Verified diagnosis of colorectal adenocarcinoma (C18.5, C19, C20).
• 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).
• Left-sided localization of the primary tumor (from the splenic flexure of the colon inclusive).
• Verified wild type KRAS, NRAS determined from tumor tissue.
• 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.

You may not qualify if:

• Previous systemic therapy for metastatic disease.
• Presence of KRAS/NRAS/V600E mutations (except for unknown BRAF status).
• Uncertain KRAS/NRAS status
• HIV infection, active hepatitis B, active hepatitis C.
• Complicated primary tumor, requiring urgent surgical intervention. After it is eliminated, the patient can participate in the study.
• The presence of a disease or condition that, in the opinion of the investigator, prevents the patient from participating in the study.
• Impossibility of organizing central venous access.

Sponsors & Collaborators

• City Clinical Oncology Hospital No 1: lead
• Atlas Biomed: collaborator
• N.N. Blokhin National Medical Research Center of Oncology: collaborator
• Moscow MultidisciplinaryClinical Center Kommunarka: collaborator

Study Sites (3)

Moscow Multidiciplinary Clinical Center Kommunarka

Moscow, 108814, Russia

RECRUITING

N.N Blokhin Cancer Reserch Center

Moscow, 115478, Russia

RECRUITING

Reutov Clinical hospital

Reutov, 143964, Russia

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Panitumumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Ilya Pokataev, phD

CONTACT

+74955369406; pokia@mail.ru

Maria Byakhova, phD

CONTACT

+79151751299; biakhovamm@mail.ru

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of department of medical oncology

Model Details: randomize and compare contol and experimental groups

Study Record Dates

• First Submitted: January 18, 2024
• First Posted: January 26, 2024
• Study Start: January 17, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: January 29, 2024

Record last verified: 2024-01

Locations

RU (3)