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Trial Title:
Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer
NCT ID:
NCT06226857
Condition:
Colorectal Neoplasms
Chemotherapy Effect
Molecular Sequence Variation
Conditions: Official terms:
Colorectal Neoplasms
Cetuximab
Panitumumab
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
randomize and compare contol and experimental groups
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cetuximab
Description:
FOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de
Gramont+cetuximab/panitumumab is allowed after 8 cycles
Arm group label:
A
Arm group label:
BC
Other name:
panitumumab
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.
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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Moscow Multidiciplinary Clinical Center Kommunarka
Address:
City:
Moscow
Zip:
108814
Country:
Russian Federation
Status:
Recruiting
Contact:
Last name:
Mikhail Fedianin, phD
Email:
fedianinmu@mail.ru
Facility:
Name:
N.N Blokhin Cancer Reserch Center
Address:
City:
Moscow
Zip:
115478
Country:
Russian Federation
Status:
Recruiting
Contact:
Last name:
Alexey Tryakin, phD
Phone:
+74993249834
Email:
atryakin@gmail.com
Facility:
Name:
Reutov Clinical hospital
Address:
City:
Reutov
Zip:
143964
Country:
Russian Federation
Status:
Recruiting
Contact:
Last name:
Mikhail Byakhov, PhD
Phone:
+7-800-550-50-30
Email:
biakhovamm@mail.ru
Start date:
January 17, 2024
Completion date:
December 31, 2027
Lead sponsor:
Agency:
City Clinical Oncology Hospital No 1
Agency class:
Other
Collaborator:
Agency:
Atlas Biomed
Agency class:
Industry
Collaborator:
Agency:
N.N. Blokhin National Medical Research Center of Oncology
Agency class:
Other
Collaborator:
Agency:
Moscow MultidisciplinaryClinical Center Kommunarka
Agency class:
Other
Source:
City Clinical Oncology Hospital No 1
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06226857
