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Taking people in ItalyPhase 3

Testing on-and-off versus continuous panitumumab with FOLFIRI for colorectal cancer

Tests on-and-off panitumumab with FOLFIRI in adults with metastatic colorectal cancer.

Key facts

Who runs it
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Where
Ancona, Avellino, Bari, Bergamo, Brescia, Caserta, Castellana Grotte, Catania, Catanzaro, Firenze, Foggia, Frattamaggiore, Genoa, Lecce, Legnano, Località la Schiana, Pozzuoli (NA), Milan, Milano, Mirabella Eclano, Naples, Padova, Palermo, Pavia, Pescara, Peschiera del Garda, Pisa, Potenza, Ragusa, Reggio Emilia, Roma, Rome, San Giovanni Rotondo, Sassari, Statte, Teramo, Torino, Tricase, and Verona, ItalySee the 48 sites
Registry title
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)
Status
Recruiting
Phase
Phase 3
People taking part
500 people, planned
Started
12 Jun 2024
Expected to end
30 Nov 2027
Type of study
Interventional
Record updated
20 October 2026

Who can take part

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults with metastatic colorectal cancer on the left side of the bowel that cannot be removed by surgery. It tests panitumumab plus FOLFIRI given on and off versus continuously, as first treatment.

Age
18 years or older
Sex
Men and women can join
Disease stage
Metastatic colorectal cancer on the left side, proven by tissue tests, judged unresectable by the local team. The disease must be measurable on scans (RECIST 1.1). ECOG performance status 1 or lower.
Earlier treatment
No earlier treatment (chemotherapy, radiation or surgery) for metastatic colorectal cancer. Surgery on the first (primary) tumor before starting is allowed. Earlier adjuvant chemotherapy is allowed if it ended more than 6 months ago.
Biomarker or test result
RAS/BRAF wild-type and pMMR and/or MSS status. Known DPYD activity is required.

Main reasons for not taking part

  • Another cancer within the last five years (a few skin and cervical exceptions)
  • Any brain metastases
  • History of interstitial pneumonitis or pulmonary fibrosis
  • History of corneal perforation or ulceration keratitis
  • Pregnancy and breast-feeding

The registry criteria, word for word

Show all 27 criteriaShow less

Who can take part

  • 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

Who cannot take part

  • 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

Where in Italy

  • A.O.U Maggiore della CaritàItalyTaking people
  • Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I G M Lancisi G SalesiAncona, ItalyTaking people
  • AORN San Giuseppe Moscati AvellinoAvellino, ItalyTaking people
  • Azienda Sanitaria Locale Della Provincia Di BariBari, ItalyTaking people
  • Istituto Tumori Bari Giovanni Paolo IIBari, ItalyTaking people
  • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIIIBergamo, ItalyTaking people
  • Fondazione PoliambulanzaBrescia, ItalyTaking people
  • Azienda Ospedaliera Sant'Anna E San Sebastiano Di CasertaCaserta, ItalyTaking people
  • National Institute of Gastroenterology Saverio De Bellis Research HospitalCastellana Grotte, ItalyTaking people
  • Ospedale GaribaldiCatania, ItalyTaking people
  • Azienda Ospedaliero Universitaria Renato DulbeccoCatanzaro, ItalyTaking people
  • Università degli Studi di Firenze-Azienda Ospedaliero Universitaria Careggi SC di Oncologia MedicalFirenze, ItalyTaking people
  • Azienda Ospedaliero Universitaria Ospedali RiunitiFoggia, ItalyTaking people
  • Ospedale Civile San Giovanni di Dio - FrattamaggioreFrattamaggiore, ItalyTaking people
  • IRCCS Ospedale Policlinico San MartinoGenoa, ItalyTaking people
  • Ospedale Vito Fazzi LecceLecce, ItalyTaking people
  • Azienda Socio Sanitaria Territoriale Ovest MilaneseLegnano, ItalyTaking people
  • Presidio Ospedaliero Santa Maria delle GrazieLocalità la Schiana, Pozzuoli (NA), ItalyTaking people
  • Azienda Ospedaliera Ospedale Niguarda Ca' GrandaMilan, ItalyTaking people
  • Azienda Socio Sanitaria Territoriale Santi Paolo E CarloMilan, ItalyTaking people
  • Fondazione IRCCS - Istituto Nazionale dei TumoriMilan, ItalyTaking people
  • Istituto Europeo di Oncologia - MilanoMilano, ItalyTaking people
  • Casa di Cura Villa MariaMirabella Eclano, ItalyTaking people
  • Azienda Ospedaliera dei ColliNaples, ItalyTaking people
  • Azienda Ospedaliera di Rilievo Nazionale Antonio CardarelliNaples, ItalyTaking people
  • Azienda Sanitaria Locale Napoli 1 CentroNaples, ItalyTaking people
  • IRCCS Istituto Nazionale Tumori Fondazione PascaleNaples, ItalyTaking people
  • Universita degli Studi della Campania Luigi VanvitelliNaples, ItalyTaking people
  • Istituto Oncologico VenetoPadova, ItalyTaking people
  • ARNAS Civico Di Cristina BenfratelliPalermo, ItalyTaking people
  • Casa di Cura Macchiarella-PalermoPalermo, ItalyTaking people
  • Fondazione IRCCS Policlinico San MatteoPavia, ItalyTaking people
  • Azienda Sanitaria Locale di PescaraPescara, ItalyTaking people
  • Ospedale P. Pederzoli Casa di Cura Privata S.p.A.Peschiera del Garda, ItalyTaking people
  • Azienda Ospedaliero Universitaria PisanaPisa, ItalyTaking people
  • Azienda Ospedaliera Regionale San CarloPotenza, ItalyTaking people
  • Ospedale ' Civile Maria Paterno' ArezzoRagusa, ItalyTaking people
  • Azienda USL IRCCS di Reggio EmiliaReggio Emilia, ItalyTaking people
  • IRCCS- Regina Elena National Cancer InstituteRoma, ItalyTaking people
  • Fondazione Policlinico Universitario Agostino Gemelli IRCCSRome, ItalyTaking people
  • San Camillo Forlanini HospitalRome, ItalyTaking people
  • Casa Sollievo della SofferenzaSan Giovanni Rotondo, ItalyTaking people
  • Azienda Ospedaliero-Universitaria di SassariSassari, ItalyTaking people
  • Ospedale S.G. MoscatiStatte, ItalyTaking people
  • Ospedale “Giuseppe Mazzini” - TeramoTeramo, ItalyTaking people
  • A.O.U. Citta della Salute e della Scienza di Torino - Ospedale MolinetteTorino, ItalyTaking people
  • Pia Fondazione Di Culto E Religione Card G PanicoTricase, ItalyTaking people
  • Azienda Ospedaliera Universitaria Integrata VeronaVerona, ItalyTaking people

About the trial

What the trial wants to find out

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.

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record

Print a page for my doctor

Data and sources

Registry record
Listed on the EU's official list of trials (CTIS).
Official title
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)
Plain-language title
Testing on-and-off versus continuous panitumumab with FOLFIRI for colorectal cancerGenerated from the registry record. The registry title is the official one.
AI summary
From the trial's eligibility criteria. Read by machine on 9 November 2026.
Record updated
20 October 2026