NCT03874026 Study of Folfiri/Cetuximab in FcGammaRIIIa V/V Stage IV Colorectal Cancer Patients
| NCT ID | NCT03874026 |
| Status | Recruiting |
| Phase | Phase 2 |
| Sponsor | National Cancer Institute, Naples |
| Condition | Colorectal Cancer |
| Study Type | INTERVENTIONAL |
| Enrollment | 34 participants |
| Start Date | 2019-09-05 |
| Primary Completion | 2023-05-19 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.
This trial targets 34 participants in total. It began in 2019-09-05 with a primary completion date of 2023-05-19.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief 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 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.
Eligibility Criteria
Inclusion Criteria: * 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; * 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. Exclusion Criteria: * 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); * 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.
Contact & Investigator
Frequently Asked Questions
Who can join the NCT03874026 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, up to 75 Years, studying Colorectal Cancer. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT03874026 trial and what does that mean for participants?
Phase 2 trials evaluate whether the treatment shows signs of effectiveness while continuing to monitor safety. More participants are enrolled than in Phase 1 to help refine the treatment protocol.
Is NCT03874026 currently recruiting?
Yes, NCT03874026 is actively recruiting participants. Contact the research team at ale.otto@libero.it for enrollment information.
Where is the NCT03874026 trial being conducted?
This trial is being conducted at Naples, Italy.
Who is sponsoring the NCT03874026 clinical trial?
NCT03874026 is sponsored by National Cancer Institute, Naples. The trial plans to enroll 34 participants.
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