Second-line FOLFIRI + Panitumumab in Subjects With Wild Type RAS Metastatic Colorectal

NCT03751176 | Unknown Phase 2

• 2 other identifiers: GEMCAD-17-012017-004519-38
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 18

Brief Summary

To estimate progression-free-survival at 6 months in subjects treated in first-line with panitumumab and FOLFOX and with wild type RAS mCRC (metastatic colorectal cancer) confirmed in liquid biopsies before starting second line treatment will be screened for this trial and who have interrupted panitumumab for \<3 months (panitumumab continuation). Control arm of subjects treated with FOLFIRI alone will be included. The combinations of 5-fluorouracil (5-FU) with oxaliplatin (FOLFOX)are considered the backbone chemotherapy for mCRC. Clinical trials have shown the benefit of adding monoclonal antibodies to subjects without mutations in RAS, directed against the epidermal growth factor receptor (EGFR) (cetuximab and panitumumab) to conventional chemotherapy as first-line treatment of mCRC. This trial purposes to study the treatment beyond progression with panitumumab in subjects treated in first-line with an anti-EGFR monoclonal antibody, or rather,the re-introduction of the same targeted therapy after progression to first line. The clinical hypothesis of this study is that the second-line regimen FOLFIRI + panitumumab, is sufficiently active (defined as a 6-months PFS higher than 30% \[based on prior results with second-line FOLFIRI alone\] and of at least 50%), justifying further study in this population.

Conditions

Colorectal Cancer Metastatic

Keywords

Clinical trial, phase II; Aged (at least 18 years old); Progression -Free - Survival; Safety; Conversion rate of RAS/BRAF status in liquid biopsy; Chemotherapy regimen; Monoclonal antibody; FOLFIRI; Panitumumab; RAS/BRAF Wild-type

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 6 months

  The proportion of subjects progression free at 6 months

  6 months after inclusion

Secondary Outcomes (5)

• Progression-free survival (PFS)

  38 months

• Overall response rate (ORR)

  38 months

• Overall survival (OS)

  38 months

• Safety and tolerability. ( assessment will consist of monitoring adverse events (AEs), including serious adverse events (SAEs) and laboratory safety parameters)

  38 months

• Biomarkers analysis by liquid biopsies.

  38 months

Study Arms (2)

FOLFIRI + panitumumab

EXPERIMENTAL

Patients received panitumumab plus FOLFIRI in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses: * Panitumumab: 6 mg/kg administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy * FOLFIRI: * Irinotecan: 180 mg/m2 as IV infusion over 90 min on day 1 * Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1 * 5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2

Drug: Panitumumab; Drug: Irinotecan; Drug: Folinic acid; Drug: 5-FU

FOLFIRI

ACTIVE COMPARATOR

Patients received FOLFIRI in 14-day cycles until disease progression, unacceptable toxicity, investigator's decision or patient withdrawal of consent, at the following doses: * Irinotecan: 180 mg/m2 as IV infusion over 90 min on day 1 * Folinic acid: (leucovorin) 200-400 mg/m2 IV over 2 hours on day 1 * 5-FU: 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2

Drug: Irinotecan; Drug: Folinic acid; Drug: 5-FU

Interventions

Panitumumab DRUG

Panitumumab 6 mg/kg will be administered by intravenous (IV) infusion over 60 min on days 1 and 14 of every cycle just before administration of chemotherapy

Also known as: Vectibix

FOLFIRI + panitumumab

Irinotecan DRUG

Irinotecan 180 mg/m2 will be administered as IV infusion over 90 min on day 1

Also known as: Any marketed

FOLFIRI; FOLFIRI + panitumumab

Folinic acid DRUG

Folinic acid 200-400 mg/m2 will be administered as IV infusion over 2 hours on day 1

Also known as: Any marketed, Leucovorin

FOLFIRI; FOLFIRI + panitumumab

5-FU DRUG

5-FU will be administered IV 400 mg/m2 bolus followed by 2400 mg/m2 IV continuous infusion over 46-48 hours on days 1 and 2

Also known as: Any marketed, 5-fluorouracil

FOLFIRI; FOLFIRI + panitumumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Man or woman at least 18 years old
• Capable of understand, sign and date an informed consent approved by an IEC (investigational Ethics Committee)
• Histologically confirmed adenocarcinoma of the colon or rectum in subjects with metastatic disease
• Having received a 1st line chemotherapy regimen for mCRC consisting of FOLFOX + panitumumab and having at least achieved stable disease ( i.e., CR (Complete Response) PR (Partial Response) or SD (stable disease) )
• Wild-type RAS tumour status confirmed in liquid biopsies before starting second-line treatment
• At least one unidimensionally measurable lesion of at least 10 mm per RECIST criteria (version 1.1)
• Subjects not candidates for metastasectomy
• Tumour disease staging according to RECIST (version 1.1) by investigator up to 4 weeks prior to start of study treatment
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Adequate bone marrow function: neutrophils ≥1.5 x109/ L; platelets ≥100 x109/L; haemoglobin ≥9 g/dL
• Hepatic, renal and metabolic function as follows:
• Total bilirubin count ≤1.5 x upper limit of normal (ULN), ALT (alanine aminotransferase) and AST (aspartate aminotransferase) \<2.5 x ULN; or in case of liver metastasis ALT and AST \<5 x ULN
• Renal function, calculated as creatinine clearance or 24-hour creatinine clearance ≥ 50 mL/min
• Magnesium \> lower limit of normal (LLN) -

You may not qualify if:

• Diagnosis of progressive disease more than 3 months after the last panitumumab administration
• First-line PFS of less than 3 months
• Subjects given less than 3 months (consecutive) of first-line panitumumab
• History of prior or concurrent central nervous system (CNS) metastases
• Prior irinotecan therapy
• Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment
• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computerised tomography
• Acute or subacute intestinal occlusion and/or active inflammatory bowel disease or other bowel disease that causes chronic diarrhoea (defined as grade ≥ 2 diarrhoea according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.03)
• Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia
• History of Gilbert disease or known dihydropyrimidine deficiency syndrome
• Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
• Treatment for systemic infection within 14 days before the start of study treatment
• History of any disease that may increase the risks associated with study participation or may interfere with the interpretation of study results
• Pregnant or breastfeeding woman
• Male or female of childbearing age who do not agree with taking adequate contraceptive precautions, i.e. use contraception double barrier (e.g., diaphragm plus condoms) or abstinence during the course of the study and for 6 months after the last administration of study drug for women and 1 month for men

Sponsors & Collaborators

• Grupo Espanol Multidisciplinario del Cancer Digestivo: lead
• Amgen: collaborator
• Pivotal S.L.: collaborator

Study Sites (18)

ICO Girona Dr. Josep Trueta

Girona, Barcelona, 17007, Spain

Location

Hospital de Granollers

Granollers, Barcelona, 08402, Spain

Location

Hospital Mutua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Hospital General Universitario de Elche

Alicante, Elche, 03203, Spain

Location

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, 28922, Spain

Location

H. Universitari Sant Joan de Reus

Reus, Tarragona, 43204, Spain

Location

Hospital de La Ribera de Alzira

Alzira, Valencia, 46600, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universtiario la Paz

Madrid, 28046, Spain

Location

CIOCC Sanchinarro

Madrid, 28050, Spain

Location

Complejo Hospitalario de Navarra

Navarro, 31008, Spain

Location

Corporació Sanitaria Parc Taulí

Sabadell, 08208, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Related Links

• GEMCAD (Grupo Español Multidisciplinar en Cancer Digestivo) web page

MeSH Terms

Interventions

Panitumumab; Irinotecan; Leucovorin; Fluorouracil

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; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Jorge Aparicio, MD

  Hospital universitari i Politecnic La Fe

  STUDY DIRECTOR

Study Design

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

Model Details: Subjects will be assigned in a 3:2 ratio to receive FOLFIRI + panitumumab (Group A) or FOLFIRI alone (Group B). Randomization will be stratified by primary tumour location (left vs right).

Study Record Dates

• First Submitted: November 20, 2018
• First Posted: November 23, 2018
• Study Start: November 8, 2018
• Primary Completion: November 30, 2020
• Study Completion: November 30, 2022
• Last Updated: June 30, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (18)