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

NCT04425239 | Completed Phase 2

• 1 other identifier: IMPROVE
• Study Type: interventional
• Target: 151
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that intermittent first-line Panitumumab plus FOLFIRI is effective as the same regimen given continuously, in unresectable metastatic RAS and BRAF wild type colorectal cancer patients. Correlative studies on tumor and blood samples could identify potential biomarkers of efficacy and help defining personalized treatment strategy.

Conditions

Colorectal Cancer Stage IV

Keywords

metastatic colorectal cancer; RAS and BRAF wild type; intermittent therapy; liquid biopsy; panitumumab

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression Free Survival on treatment (PFSOT) is defined as the time from randomization to the first objective disease progression documented in patients undergoing treatment cycle (objective disease progression during treatment free intervals are excluded) or death due to any cause, whichever occurs first.

  up to 1 year last patients randomized

Secondary Outcomes (1)

• Overall Survival (OS)

  up to 1 year last patients randomized

Other Outcomes (9)

• Toxicities

  up to 1 year last patients randomized

• Assessment of patients'-health-related quality of life

  up to 6 months last patients randomized

• Overall Response Rate

  up to 1 year last patients randomized

Study Arms (2)

CONTINUOUS ARM:

ACTIVE COMPARATOR

Patients will receive Panitumumab plus FOLFIRI until progressive disease, unacceptable toxicity or informed consent withdrawal.

Drug: Panitumumab

INTERMITTENT ARM:

EXPERIMENTAL

Patients will have a treatment free interval until progressive disease (PD), when they will receive up to 8 cycles of Panitumumab plus FOLFIRI. In the presence of complete or partial response, or stable disease, non-progressing patients will undergo again to treatment free interval until PD, when they will restart treatment. Treatment cycling will continue till any PD on treatment.

Drug: Panitumumab

Interventions

Panitumumab DRUG

Continuous administation

Also known as: Irinotecan, Fluorouracil plus folinic acid

INTERMITTENT ARM:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent to study procedures and to molecular analyses;
• Histologically proven diagnosis of colorectal cancer with wildtype RAS and BRAF status in certified laboratories;
• Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;
• At least one measurable lesion according to RECIST1.1 criteria;
• Availability of a tumor sample (primary and/or metastatic sites) for exploratory research;
• Age ≥ 18 years;
• ECOG PS ≤ 2;
• Life expectancy of at least 12 weeks;
• Previous adjuvant chemotherapy allowed only if more than 6 months elapsed between the end of adjuvant and first relapse;
• Neutrophils ≥ 1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl;
• Total bilirubin ≤1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or \< 5 x UNL in case of liver metastases) alkaline phosphatase ≤ 2.5 x UNL (or \< 5 x UNL in case of liver metastases);
• Creatinine clearance ≥50 mL/min or serum creatinine ≤ 1.5 x UNL;
• Female with a childbearing potential and male subjects must be willing to use adequate contraception (barrier contraceptive measure, oral contraception, intrauterine device);
• Will and ability to comply with the protocol.

You may not qualify if:

• Previous treatment for metastatic disease;
• Radiotherapy to any site within 4 weeks before the study;
• Any contraindication to use Panitumumab, Irinotecan, 5-FU or folinic acid
• Known or clinically suspected brain metastases.
• History or evidence upon physical examination of CNS disease unless adequately treated.
• Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks.
• Diagnosis of interstitial pneumonitis or pulmonary fibrosis;
• Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration or which, in the investigating physician's opinion, rules out the patient's participation in the study;
• Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication;
• Treatment with any investigational drug within 30 days prior to enrolment;
• Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ;
• Lack of physical integrity of the gastrointestinal tract or history of acute or sub-acute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhea.
• Disease that is deemed potentially resectable.
• Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.
• Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

Istituto Nazionale Tumori di Napoli - IRCCS - Fondazione G. Pascale

Napoli, 80131, Italy

Location

Related Publications (1)

• Avallone A, Giuliani F, De Stefano A, Santabarbara G, Nasti G, Montesarchio V, Rosati G, Cassata A, Leo S, Romano C, Tamburini E, Silvestro L, Lotesoriere C, Nappi A, Santini D, Petrillo A, Colombo A, Febbraro A, Leone A, Mannavola F, Laterza MM, Izzo F, Sobrero A, Delrio P, Giannarelli D, Budillon A. Intermittent or Continuous Panitumumab Plus Fluorouracil, Leucovorin, and Irinotecan for First-Line Treatment of RAS and BRAF Wild-Type Metastatic Colorectal Cancer: The IMPROVE Trial. J Clin Oncol. 2025 Mar;43(7):829-839. doi: 10.1200/JCO.24.00979. Epub 2024 Nov 22.

  PMID: 39576946 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; Irinotecan; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Antonio Avallone, MD

  Istituto Nazionale dei Tumori di Napoli - IRCCS - Fondazione G. Pascale

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2020
• First Posted: June 11, 2020
• Study Start: May 21, 2018
• Primary Completion: July 2, 2021
• Study Completion: April 3, 2022
• Last Updated: April 7, 2022

Record last verified: 2021-09

Locations

IT (1)