Colorectal CancerPhase 2CIFRANCT03874026
Study of Folfiri/Cetuximab in FcGammaRIIIa V/V Stage IV Colorectal Cancer Patients
A Phase 2 study testing Folfiri/Cetuximab in people with Colorectal Cancer and ADCC, run by National Cancer Institute, Naples at 1 site in Italy.
Trial summary
Patients' selection thorough the identification of predictive factors still represent a challenge in metastatic colorectal cancer (mCRC). Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicit both… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer, ADCC
- What is being tested?
- Folfiri/Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteItaly
- Study dates
- 5 Sep 2019to Sep 2025
- Phase
- Phase 2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cytological or histological diagnosis of colorectal adenocarcinoma;
- KRAS, NRAS, BRAF wild-type;
- FcγRIIIaV/V genotype;
- stage IV;
- age <75 years;
- at least 1 measurable lesion;
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- ECOG (Eastern Cooperative Oncology Group) Performance Status 0 or 1;
- life expectancy> 3 months;
- negative pregnancy test for all potentially childbearing women;
- written informed consent.
Who cannot join
- previous systemic anti-tumor treatment (allowed treatment with capecitabine or fluorouracil and radiotherapy in the neoadjuvant setting of rectal tumors with therapy terminated at least 6 months before);
- presence of primary non-treated stenosing colorectal neoplasm;
- neutrophils <2000/mm³ or platelets <100.000/mm³ or hemoglobin <9 g/dl;
- serum creatinine level> 1.5 times the maximum normal value;
- GOT (glutamic oxaloacetic transaminase) and/or GPT (glutamic pyruvic transaminase) >5 times the maximum normal value and/or bilirubin level >3 times the maximum normal value;
- previous malignant neoplasms (excluding basal or spinocellular cutaneous carcinoma or in situ carcinoma of the uterine cervix);
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- active or uncontrolled infections;
- other concomitant uncontrolled diseases or conditions contraindicating the study - drugs at clinician evaluation;
- presence of brain metastases;
- refusal or inability to provide informed consent;
- impossibility to guarantee follow-up.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Cetuximab, Irinotecan and Fluorouracile in FiRst-line Treatment of Immunologically-selected Advanced Colorectal Cancer Patients: the CIFRA Study
Patients' selection thorough the identification of predictive factors still represent a challenge in metastatic colorectal cancer (mCRC). Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicit both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1 (Immunoglobulins Gamma subclass 1). Interestingly, the high-affinity FcγRIIIa (FcγR type IIIa) V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity. CIFRA is a single arm, open-label, phase II study assessing the activity of cetuximab in combination with irinotecan and fluorouracile in FcγRIIIa V/V patients with KRAS (Kirsten RAt Sarcoma), NRAS (Neuroblastoma Rat Sarcoma), BRAF (B-Rapidly Accelerated Fibrosarcoma) wild type mCRC. The study is designed with a two-stage Simon model based on a hypothetical higher response rate (+10%) of FcγRIIIa V/V patients as compared to previous trials (about 60%) assuming ADCC as one of the mechanisms of cetuximab action. The test power is 95%, the alpha value of the I-type error is 5%. With these assumptions the sample for passing the first stage is 14 patients with >6 responses and the final sample is 34 patients with >18 responses to draw positive conclusions. Secondary objectives include toxicity, responses' duration, progression-free and overall survival. Furthermore, an associated translational study will assess the patients' cetuximab-mediated ADCC and characterize the tumor microenvironment.
The CIFRA study will determine whether ADCC contributes to cetuximab activity in mCRC patients selected on an innovative immunological screening. Data from the translational study will support results'interpretation as well as provide new insights in host-tumor interactions and cetuximab activity.
- Conditions
- Colorectal Cancer, ADCC
- Being tested
- Folfiri/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.
Folfiri/CetuximabDrug
Cetuximab 400 mg/mq intravenously (iv) with "load" dose of 400 mg/mq at the first cycle followed by 250 mg/mq iv weekly by iv infusion in 90 minutes. The administration of irinotecan will precede that of cetuximab and will consist on a dose of 180 mg/mq iv in 60 minutes every two weeks and it will be followed by fluorouracil (5-FU) at a dose of 400 mg/mq in slow iv bolus at half of lederfolin 200 mg/mq 2-hours infusion. At the end of the infusion of lederfolin an elastomeric pump loaded with 5-FU 2400 mg/mq in continuous 46 hours iv infusion will be applied. Only at the first administration of CT ("load" dose of cetuximab), irinotecan will not be administered.
| Study group | Role | What they receive |
|---|---|---|
| Folfiri/Cetuximab | Experimental | Cetuximab 400 mg/mq intravenously (iv) with "load" dose of 400 mg/mq at the first cycle followed by 250 mg/mq iv weekly by iv infusion in 90 minutes. The administration of irinotecan will precede that of cetuximab and will consist on a dose of 180 mg/mq iv in 60 minutes every two weeks and it will be followed by fluorouracil (5-FU) at a dose of 400 mg/mq in slow iv bolus at half of lederfolin 200 mg/mq 2-hours infusion. At the end of the infusion of lederfolin an elastomeric pump loaded with 5-FU 2400 mg/mq in continuous 46 hours iv infusion will be applied. Only at the first administration of CT ("load" dose of cetuximab), irinotecan will not be administered. Receives: Drug: Folfiri/Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Activity
Activity assessed by RECIST criteria version 1.1
Measured: 1 year
Secondary outcomes (4)
Response duration
Time elapsed from date of response to progression occurrence.
Measured: 1 year
Progression-free survival (PFS)
PFS will be determined from the date of treatment start until progression.
Measured: Through study completion, an average of 1 year
Overall survival (OS)
OS will be measured from treatment start until death from any cause.
Measured: Through study completion, an average of 2 years
Toxic effects
Toxic effects assessed by CTCAE of the National Cancer Institute, version 4.0, June 14, 2010
Measured: At the end of Cycle 1 (each cycle is 14 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2019
- Study start5 Sep 2019
- Primary completion19 May 2023
- Study completionSep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute, Naples
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03874026
- Sponsor's protocol ID
- 60/18
- Acronym
- CIFRA
- Status last verified
- Nov 2024
- First submitted
- 26 Feb 2019
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cetuximab, Irinotecan and Fluorouracile in FiRst-line Treatment of Immunologically-selected Advanced Colorectal Cancer Patients: the CIFRA Study
- ClinicalTrials.gov ID
- NCT03874026
- Acronym / sponsor ID
- CIFRA / 60/18
- Conditions
- Colorectal Cancer, ADCC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- National Cancer Institute, NaplesUniversity, hospital or other
- Study start
- 5 Sep 2019 (actual)
- Primary completion
- 19 May 2023 (actual)
- Study completion
- Sep 2025 (estimated)
- First posted
- 14 Mar 2019 (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' selection thorough the identification of predictive factors still represent a challenge in metastatic colorectal cancer (mCRC). Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicit both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1 (Immunoglobulins Gamma subclass 1). Interestingly, the high-affinity FcγRIIIa (FcγR type IIIa) V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity. CIFRA is a single arm, open-label, phase II study assessing the activity of cetuximab in combination with irinotecan and fluorouracile in FcγRIIIa V/V patients with KRAS (Kirsten RAt Sarcoma), NRAS (Neuroblastoma Rat Sarcoma), BRAF (B-Rapidly Accelerated Fibrosarcoma) wild type mCRC. The study is designed with a two-stage Simon model based on a hypothetical higher response rate (+10%) of FcγRIIIa V/V patients as compared to previous trials (about 60%) assuming ADCC as one of the mechanisms of cetuximab action. The test power is 95%, the alpha value of the I-type error is 5%. With these assumptions the sample for passing the first stage is 14 patients with >6 responses and the final sample is 34 patients with >18 responses to draw positive conclusions. Secondary objectives include toxicity, responses' duration, progression-free and overall survival. Furthermore, an associated translational study will assess the patients' cetuximab-mediated ADCC and characterize the tumor microenvironment.
The CIFRA study will determine whether ADCC contributes to cetuximab activity in mCRC patients selected on an innovative immunological screening. Data from the translational study will support results'interpretation as well as provide new insights in host-tumor interactions and cetuximab activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Folfiri/Cetuximab | Experimental | Drug: Folfiri/CetuximabCetuximab 400 mg/mq intravenously (iv) with "load" dose of 400 mg/mq at the first cycle followed by 250 mg/mq iv weekly by iv infusion in 90 minutes. The administration of irinotecan will precede that of cetuximab and will consist on a dose of 180 mg/mq iv in 60 minutes every two weeks and it will be followed by fluorouracil (5-FU) at a dose of 400 mg/mq in slow iv bolus at half of lederfolin 200 mg/mq 2-hours infusion. At the end of the infusion of lederfolin an elastomeric pump loaded with 5-FU 2400 mg/mq in continuous 46 hours iv infusion will be applied. Only at the first administration of CT ("load" dose of cetuximab), irinotecan will not be administered. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Cytological or histological diagnosis of colorectal adenocarcinoma;
- KRAS, NRAS, BRAF wild-type;
- FcγRIIIaV/V genotype;
- stage IV;
- age <75 years;
Key exclusion criteria (11 listed)
- previous systemic anti-tumor treatment (allowed treatment with capecitabine or fluorouracil and radiotherapy in the neoadjuvant setting of rectal tumors with therapy terminated at least 6 months before);
- presence of primary non-treated stenosing colorectal neoplasm;
- neutrophils <2000/mm³ or platelets <100.000/mm³ or hemoglobin <9 g/dl;
- serum creatinine level> 1.5 times the maximum normal value;
- GOT (glutamic oxaloacetic transaminase) and/or GPT (glutamic pyruvic transaminase) >5 times the maximum normal value and/or bilirubin level >3 times the maximum normal value;
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 |
|---|---|---|
| Folfiri/CetuximabCetuximab 400 mg/mq intravenously (iv) with "load" dose of 400 mg/mq at the first cycle followed by 250 mg/mq iv weekly by iv infusion in 90 minutes. The administration of irinotecan will precede that of cetuximab and will consist on a dose of 180 mg/mq iv in 60 minutes every two weeks and it will be followed by fluorouracil (5-FU) at a dose of 400 mg/mq in slow iv bolus at half of lederfolin 200 mg/mq 2-hours infusion. At the end of the infusion of lederfolin an elastomeric pump loaded with 5-FU 2400 mg/mq in continuous 46 hours iv infusion will be applied. Only at the first administration of CT ("load" dose of cetuximab), irinotecan will not be administered. | Drug | Folfiri/Cetuximab |
Primary outcome
Activity
Time frame: 1 year
Activity assessed by RECIST criteria version 1.1
4 secondary outcomes
Response duration
Time frame: 1 year
Progression-free survival (PFS)
Time frame: Through study completion, an average of 1 year
Overall survival (OS)
Time frame: Through study completion, an average of 2 years
Toxic effects
Time frame: At the end of Cycle 1 (each cycle is 14 days)
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 7 Nov 2024.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Folfiri/Cetuximab in people with Colorectal Cancer and ADCC, run by National Cancer Institute, Naples at 1 site in Italy.
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 10 inclusion and 11 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 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Alessandro Ottaiano, MD (+39 081 5903510, ale.otto@libero.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Activity (time frame: 1 year). 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 7 Nov 2024.