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

NCT06509126 | Recruiting Phase 3

• 1 other identifier: IMPROVE-2
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that intermittent first-line Panitumumab plus FOLFIRI is effective in first line as the same regimen given continuously, resulting in a Time to Treatment Failure (TTF) not inferior to that obtained with standard continuous regimen of Panitumumab plus FOLFIRI, in the treatment of metastatic left sided RAS/B-RAF wild-type colorectal cancer patients. Correlative mechanistic studies on tissue and blood samples, liquid biopsies, could identify potential biomarkers of efficacy and help understanding the evolutionary dynamics of tumors in response to therapy thus optimizing the treatment approach with a personalized anti-EGFR treatment strategy.

Conditions

Colorectal Cancer Stage IV

Keywords

Metastatic colorectal cancer; Left sided; RAS and BRAF wild type; Intermittent therapy; Liquid biopsy; Panitumumab

Outcome Measures

Primary Outcomes (1)

• Time to Treatment Failure

  Time to treatment failure (TTF) is defined as the time from randomization to the objective disease progression by RECIST 1.1 criteria occurred during the treatment (objective disease progression during treatment free intervals are excluded) or death due to any cause, whichever occurs first, or a treatment delay \> 28 days for toxicity

  up to 1 year last patients randomized

Secondary Outcomes (1)

• Overall survival

  up to 1 year last patients randomized

Other Outcomes (11)

• Objective Tumor Response Rate

  up to 1 year last patients randomized

• Disease Control Rate

  up to 1 year last patients randomized

• Depth of Response

  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; Drug: Irinotecan; Drug: 5-fluorouracil; Drug: L-folinic acid

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; Drug: Irinotecan; Drug: 5-fluorouracil; Drug: L-folinic acid

Interventions

Panitumumab DRUG

Administered at the dosage of 6mg/kg as 60 minutes, or 90 minutes for doses over 1000 mg, intravenous infusion

Also known as: Vectibix

CONTINUOUS ARM; INTERMITTENT ARM

Irinotecan DRUG

Administered at the dosage of 180 mg/m2 over 60 minutes intravenous infusion

Also known as: Campto

CONTINUOUS ARM; INTERMITTENT ARM

5-fluorouracil DRUG

Administered at the dosage of 400 mg/m2 (bolus intravenous infusion) followed by continuous intravenous infusion over 46 hours at the dosage of 2400 mg/m2

Also known as: 5-FU

CONTINUOUS ARM; INTERMITTENT ARM

L-folinic acid DRUG

Administered at the dosage of 200 mg/m2 over 120 minutes as intravenous infusion

Also known as: LFA

CONTINUOUS ARM; INTERMITTENT ARM

Eligibility Criteria

• Age: 18 Years - 100 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 correlative studies.
• Histologically proven left sided mCRC.
• RAS/BRAF wild-type and pMMR and/or MSS status assessed at local centers according 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
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at study entry.
• Imaging-documented measurable disease, according to RECIST 1.1 criteria.
• 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

You may not qualify if:

• 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.
• 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.
• 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.
• 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.
• 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.
• Participation in any interventional drug or medical device study within 30 days prior to treatment start.
• 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.
• History of interstitial pneumonitis or pulmonary fibrosis.
• History of corneal perforation or ulceration keratitis

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

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

Napoli, 80131, Italy

RECRUITING

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 Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2024
• First Posted: July 19, 2024
• Study Start: June 12, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 19, 2024

Record last verified: 2024-06

Locations

IT (1)