FOLFIRI + Panitumumab First-line Treatment in Elderly Patients With Unresectable Metastatic Colorectal Cancer, RAS/BRAF Wild-type and Good Performance Status

NCT03142516 | Completed Phase 2

• 2 other identifiers: GEMCAD-16-032017-001639-38
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 12

Brief Summary

To estimate progression-free survival at one year in elderly patients with RAS/BRAF wild-type unresectable mCRC and good performance status treated with FOLFIRI + panitumumab as first-line therapy. The clinical hypothesis of this study is that the combination of panitumumab and FOLFIRI is a good treatment option in elderly patients with good performance status and RAS/BRAF wild-type unresectable mCRC. Another purpose of this clinical trial is to determine the RAS/BRAF mutation status in liquid biopsies at baseline and at the time of disease progression.

Conditions

Colorectal Neoplasms; Colorectal Carcinoma; Colorectal Cancer Metastatic; Neoplasm Metastasis

Keywords

Clinical Trial, Phase II; Elderly; Aged; Disease-Free Survival; Safety; Tolerability; Chemotherapy regimen; Monoclonal antibody; FOLFIRI; Panitumumab; RAS/BRAF Wild-type

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at one year

  Percentage of subjects still alive and progression free 12 months after inclusion in the study

  12 months after inclusion

Secondary Outcomes (11)

• Progression-free survival (PFS)

  42 months

• Objective response rate

  42 months

• Disease control rate

  42 months

• Duration of response

  42 months

• Time to response

  18 months

Other Outcomes (2)

• RAS/BRAF conversion proportion

  At treatment initiation and at the time of PD (42 months)

• RAS/BRAF mutations' detection proportion

  At baseline

Study Arms (1)

FOLFIRI + panitumumab

EXPERIMENTAL

All patients will receive panitumumab plus FOLFIRI for disease control 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: 150 mg/m2 as IV infusion over 90 min on day 1of first treatment cycle. If tolerance of this first dose is good, it will be scaled to a full dose of 180 mg/m2 starting from the second treatment cycle. * 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

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 150 mg/m2 will be administered as IV infusion over 90 min on day 1of first treatment cycle. If tolerance of this first dose is good, it will be scaled to a full dose of 180 mg/m2 starting from the second treatment cycle

Also known as: Any marketed

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: Leucovorin, Any marketed

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: 5-fluorouracil, Any marketed

FOLFIRI + panitumumab

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Males or females ≥ 70 years,
• Able to understand, sign and date an informed consent form approved by the IEC,
• Histologically confirmed colorectal carcinoma with metastatic disease,
• No previous treatment for metastatic disease,
• Patients starting therapy with FOLFIRI + panitumumab with a treatment aim other than achieving potential resectability of the disease,
• Independence in activities of daily living (ADL) based on the Katz Index and in instrumental activities of daily living (IAL) based on the Lawton Index,
• Having no or only one comorbidity according to the Charlson Comorbidity Index. The following ones are not considered comorbidities as long as it is provided they are adequately controlled with medication: gastroduodenal ulcer, diabetes without target organs' damage, chronic respiratory disease and connective tissue disease.
• Presence of at least one unidimensional measurable lesion ≥ 10 mm according to RECIST criteria (version 1.1),
• ECOG (Eastern Cooperative Oncology Group) performance status of 0-1,
• Adequate bone marrow function: neutrophils ≥ 1.5 x 10\^9/l; platelets ≥ 100 x 10\^9/l; haemoglobin ≥ 9 g/dl,
• Hepatic, renal and metabolic function as follows:
• Total bilirubin count ≤ 1.5 x ULN; ALT and AST \< 5 x ULN;
• Renal function, calculated creatinine clearance or 24-hour creatinine clearance ≥ 50 ml/min;
• Magnesium \> LLN

You may not qualify if:

• Diagnosed or suspected central nervous system (CNS) metastasis,
• Patients with initially resectable metastases at the time of diagnosis of metastatic disease.
• Prior treatment with irinotecan,
• Prior adjuvant chemotherapy for colorectal cancer terminated less than 6 months before metastatic disease was diagnosed,
• Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (eg, cetuximab), anti- vascular endothelial growth factor (VEGF) or treatment with small molecule EGFR inhibitors (eg, erlotinib),
• Evidence of previous acute hypersensitivity reaction of any grade to any of the components of the treatment,
• History of interstitial lung disease or pulmonary fibrosis or signs of interstitial lung disease or pulmonary fibrosis on baseline CT,
• Presence of geriatric syndromes, defined as dementia, repeated falls, fecal incontinence or urinary incontinence,
• Acute or subacute bowel obstruction and/or active bowel disease or another bowel disease causing chronic diarrhoea (defined as diarrhoea of grade ≥ 2 according to the NCI (National Cancer Institute) Common Terminology Criteria for Adverse Events (CTCAE version 4.03),
• History of Gilbert's syndrome or dihydropyrimidine dehydrogenase deficiency,
• Positive test result for human immunodeficiency virus, hepatitis C virus, chronic active hepatitis B infection,
• Treatment for systemic infection within 14 days prior to the start of the study treatment,
• Clinically significant sensory peripheral neuropathy,
• Any concurrent disease that may increase the risk associated with study participation or may interfere with the interpretation of study results,
• Males whose partner is of child-bearing age and who does not agree to use adequate contraceptive precautions, i.e. double-barrier methods (e.g. diaphragm plus condom) or abstinence for the duration of the study and for 1 month after the last administration of the study drug,

Sponsors & Collaborators

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

Study Sites (12)

ICO L´Hospitalet de Llobregat - Hospital Durán i Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Sant Joan Despí-Moises Broggi

Sant Joan Despí, Barcelona, 08970, Spain

Location

Hospital Universitario Puerta de Hierro-Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Rey Juan Carlos

Móstoles, Madrid, 28933, Spain

Location

Hospital Clínic

Barcelona, 08036, Spain

Location

Hospital General Universitario de Elda

Elda, 03600, Spain

Location

Hospital Universitario Arnau de Vilanova

Lleida, 25198, Spain

Location

Hospital Universitario la Paz

Madrid, 28046, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario Son Espases

Palma, 07020, Spain

Location

Hospital Parc Taulí

Sabadell, 08208, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, 50009, Spain

Location

Related Links

• GEMCAD web page

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

Panitumumab; Irinotecan; Leucovorin; Fluorouracil

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

• Jaime Feliu, MD

  Hospital Universitario La Paz

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: May 5, 2017
• Study Start: October 31, 2017
• Primary Completion: January 21, 2021
• Study Completion: January 21, 2021
• Last Updated: June 21, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (12)