Colorectal NeoplasmsPhase 3CRC01NCT06226857
Other Oncogene Mutations for Anti-EGFR Efficacy in Patients With Left-sided RAS-wild Type Metastatic Colorectal Cancer
A Phase 3 study testing Cetuximab in people with Colorectal Neoplasms and Chemotherapy Effect, run by City Clinical Oncology Hospital No 1 at 3 sites in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Colorectal Neoplasms, Chemotherapy Effect, Molecular Sequence Variation
- What is being tested?
- Cetuximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 355 participants
- Where
- 3 sitesRussia
- Study dates
- 17 Jan 2024to 31 Dec 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
- 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.
Who cannot join
- Previous systemic therapy for metastatic disease.
- Presence of KRAS/NRAS/V600E mutations (except for unknown BRAF status).
- Uncertain KRAS/NRAS status
- 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.
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Russia3 sites, 3 recruiting
- Recruiting
Moscow Multidiciplinary Clinical Center Kommunarka
Moscow, 108814
Mikhail Fedianin, phD, fedianinmu@mail.ru
- Recruiting
N.N Blokhin Cancer Reserch Center
Moscow, 115478
Alexey Tryakin, phD, +74993249834, atryakin@gmail.com
- Recruiting
Reutov Clinical hospital
Reutov, 143964
Mikhail Byakhov, PhD, +7-800-550-50-30, biakhovamm@mail.ru
About this study
Official title: 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.
Read the 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.
- Being tested
- Cetuximab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called panitumumab
FOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de Gramont+cetuximab/panitumumab is allowed after 8 cycles
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival
Intention to treat, Calculated from start of therapy to date of disease progression or death
Measured: through study completion, an average of 3 years
Secondary outcomes (3)
edverse events
all AE based on CTC criteria v. 5
Measured: through study completion, an average of 3 years
overall survival
Calculated from start of therapy to date of last contact or death
Measured: through study completion, an average of 3 years
progression-free survival based (per protocol)
Measured: through study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2024
- Study start17 Jan 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomize and compare contol and experimental groups
- Masking
- None (open label)
- Enrolment
- 355 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City Clinical Oncology Hospital No 1
- Sponsor type
- Other government
- Collaborators
- Atlas Biomed, N.N. Blokhin National Medical Research Center of Oncology, Moscow Multidisciplinary Clinical Center "Kommunarka"
- Responsible party
- Principal investigator, Pokataev Ilya, City Clinical Oncology Hospital No 1
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06226857
- Sponsor's protocol ID
- CRC01
- Other IDs
- 2102-2/23
- Acronym
- CRC01
- Status last verified
- Jan 2024
- First submitted
- 18 Jan 2024
- Last updated
- 29 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06226857
- Acronym / sponsor ID
- CRC01 / CRC01
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 355 participants (estimated)
- Lead sponsor
- City Clinical Oncology Hospital No 1Other government
- Collaborators
- Atlas Biomed, N.N. Blokhin National Medical Research Center of Oncology, Moscow Multidisciplinary Clinical Center "Kommunarka"
- Study start
- 17 Jan 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 26 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- randomize and compare contol and experimental groups
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: CetuximabAll 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. |
| BC | Experimental | Drug: CetuximabAll 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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).
Key exclusion criteria (8 listed)
- Previous systemic therapy for metastatic disease.
- Presence of KRAS/NRAS/V600E mutations (except for unknown BRAF status).
- Uncertain KRAS/NRAS status
- 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.
- HIV infection, active hepatitis B, active hepatitis C.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabAlso: panitumumabFOLFOX+cetuximab/panitumumab q2w until desease progression, deescalation to de Gramont+cetuximab/panitumumab is allowed after 8 cycles | Drug | A, BC |
Primary outcome
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
3 secondary outcomes
edverse events
Time frame: through study completion, an average of 3 years
overall survival
Time frame: through study completion, an average of 3 years
progression-free survival based (per protocol)
Time frame: through study completion, an average of 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cetuximab in people with Colorectal Neoplasms and Chemotherapy Effect, run by City Clinical Oncology Hospital No 1 at 3 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ilya Pokataev, phD (+74955369406 ext. 2007, pokia@mail.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression-free survival (time frame: through study completion, an average of 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2024.