Intermittent or Continuous Panitumumab Plus FOLFIRI for Left Sided RAS/B-RAF Wild-type Metastatic Colorectal Cancer

Launched by NATIONAL CANCER INSTITUTE, NAPLES · Jul 11, 2024

Keywords

ClinConnect Summary

This clinical trial is studying two ways to give a cancer treatment called Panitumumab combined with FOLFIRI for patients with advanced colorectal cancer that is located on the left side of the colon and has specific genetic characteristics (known as RAS/BRAF wild-type). The researchers want to find out if giving this treatment intermittently (in cycles) is just as effective as giving it continuously (without breaks). They hope that this approach will help patients have a similar amount of time before their treatment stops working.

To participate in this trial, you need to be at least 18 years old and have a confirmed diagnosis of unresectable (unable to be surgically removed) left-sided colorectal cancer. You should not have received any prior treatments for this type of cancer, and your overall health should be good enough to tolerate the study treatments. Participants will receive the study treatment and may also provide blood and tissue samples to help researchers understand how the treatment works and identify factors that could predict its effectiveness. This trial is currently recruiting participants, and it aims to personalize cancer treatment based on individual responses to therapy.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Written informed consent to study procedures and to correlative studies.
• • 2. Histologically proven left sided mCRC.
• • 3. RAS/BRAF wild-type and pMMR and/or MSS status assessed at local centers according a validated method defined by EMA
• • 4. Disease judged unresectable by the local multidisciplinary team
• • 5. Patient candidate to receive Induction treatment with FOLFIRI plus panitumumab as per standard clinical practice
• • 6. No prior treatments (chemotherapy, radiation or surgery) for mCRC. Surgery for primary CRC tumor before starting treatment is allowed.
• • 7. Either sex aged ≥ 18
• • 8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at study entry.
• • 9. Imaging-documented measurable disease, according to RECIST 1.1 criteria.
• • 10. Known dihydropyrimidine dehydrogenase (DPYD) activity is mandatory. Additional analysis of polymorphisms uridine diphosphate-glycosyltransferase 1 (UGT1A1) enzyme is recommended but not mandatory
• • 11. Adequate bone marrow hematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥ 100 x 109/L and hemoglobin ≥ 9 g/dL.
• • 12. Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 2 (in case of biliary stent) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 X ULN.
• • 13. Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula).
• • 14. Electrolytes (i.e. magnesium, calcium, sodium and potassium) within laboratory normal range
• Exclusion Criteria:
• • 1. Prior malignancy within five years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• • 2. Prior chemotherapy or any other medical treatment for mCRC (previous adjuvant chemotherapy is allowed if terminated \> 6 months previously).
• • 3. Major surgical intervention within 4 weeks prior to enrollment.
• • 4. Pregnancy and breast-feeding.
• • 5. Any brain metastases.
• • 6. Complete deficiency of activity of dihydropyrimidine dehydrogenase (DPYD) or known UGT1A1 homozygosity.
• • 7. Required dose reduction of 5-fluorouracil in the past for toxicity.
• • 8. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, or would interfere with the results of the study.
• • 9. History of poor co-operation, non-compliance with medical treatment, unreliability or any condition that may impair the patient's understanding of the Informed consent form.
• • 10. Participation in any interventional drug or medical device study within 30 days prior to treatment start.
• • 11. Sexually active males and females (of childbearing potential) unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.
• • 12. History of interstitial pneumonitis or pulmonary fibrosis.
• • 13. History of corneal perforation or ulceration keratitis