Randomized phase 3 study of intermittent or continuous Panitumumab plus FOLFIRI for first-line treatment of patients with unresectable left sided RAS/B-RAF wild-type metastatic colorectal cancer (IMPROVE-2 trial)

Trial details

Who runs it

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Trial code

EU 2023-509551-14-00

Record updated

2026. október 20.

Original description

To investigate whether experimental intermittent treatment of Panitumumab plus FOLFIRI (given until progression during treatment or inacceptable toxicity) results effective in first line as the same regimen given continuously, in the treatment of metastatic left sided RAS/B-RAF wild-type colorectal cancer patients. To assess whether an improvement in safety, tolerability and quality of life can be achieved in the intermittent arm as compared to the continuous arm. To explore potential biomarkers of primary and secondary resistance as well as to monitor treatment efficacy and toxicity on both tissue, primary tumors and resected metastases when available, and blood samples.Read full original descriptionShow less

To investigate whether experimental intermittent treatment of Panitumumab plus FOLFIRI (given until progression during treatment or inacceptable toxicity) results effective in first line as the same regimen given continuously, in the treatment of metastatic left sided RAS/B-RAF wild-type colorectal cancer patients. To assess whether an improvement in safety, tolerability and quality of life can be achieved in the intermittent arm as compared to the continuous arm. To explore potential biomarkers of primary and secondary resistance as well as to monitor treatment efficacy and toxicity on both tissue, primary tumors and resected metastases when available, and blood samples.

Inclusion: Written informed consent to study procedures and to correlative studies; Known dihydropyrimidine dehydrogenase (DPYD) activity is mandatory. Additional analysis of polymorphisms uridine diphosphate-glycosyltransferase 1 (UGT1A1) enzyme is recommended but not mandatory; 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; 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; 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); Electrolytes (i.e. magnesium, calcium, sodium and potassium) within laboratory normal range; Histologically proven left sided mCRC; RAS/BRAF wild-type and pMMR and/or MSS status assessed at local centers according to a validated method defined by EMA; Disease judged unresectable by the local multidisciplinary team; Patient candidate to receive Induction treatment with FOLFIRI plus panitumumab as per standard clinical practice; No prior treatments (chemotherapy, radiation or surgery) for mCRC. Surgery for primary CRC tumor before starting treatment is allowed; Either sex aged ≥ 18 years; Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 at study entry; Imaging-documented measurable disease, according to RECIST 1.1 criteria.

Exclusion: Participation in any interventional drug or medical device study within 30 days prior to treatment start; Prior chemotherapy or any other medical treatment for mCRC (previous adjuvant chemotherapy is allowed if terminated > 6 months previously); Major surgical intervention within 4 weeks prior to enrollment; 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; 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; History of interstitial pneumonitis or pulmonary fibrosis; History of corneal perforation or ulceration keratitis; 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; 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; Pregnancy and breast-feeding; Any brain metastases; Complete deficiency of activity of dihydropyrimidine dehydrogenase (DPYD) or known UGT1A1 homozygosity; Required dose reduction of 5-fluorouracil in the past for toxicity.

EU CTIS 2023-509551-14-00