Study of FOLFIRI + Panitumumab Using Ultra-selection Technology of Patients With Stage IV Colorectal Cancer Refractory to Irinotecan Without Any Mutation on KRAS, PIK3Ca, BRAF and NRAS Genes Detected With Highly Sensitive Techniques

NCT01704703 | Completed Phase 2

• 2 other identifiers: TTD-12-032012-001955-38
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Open label Phase II study of FOLFIRI + Panitumumab using ultra-selection technology with next generation high sensitivity genotyping of patients with stage IV colorectal cancer refractory to irinotecan without any mutation on KRAS, PIK3Ca, BRAF and NRAS genes detected with highly sensitive techniques.

Conditions

Stage IV Colorectal Cancer

Keywords

colorectal cancer; FOLFIRI; Panitumumab; KRAS, PIK3Ca,BRAF and NRAS genes; highly sensitive techniques

Outcome Measures

Primary Outcomes (1)

• Objective response rate (TRO)

  4 years

Secondary Outcomes (9)

• disease control rate (TCE)

  4 years

• duration of response (DR)

  4 years

• time to response(THR)

  4 years

• time to progression (THP)

  4 years

• time to treatment failure (THF)

  4 years

Study Arms (1)

Experimental

EXPERIMENTAL

FOLFIRI + panitumumab

Drug: panitumumab; Drug: FOLFIRI

Interventions

panitumumab DRUG

Panitumumab 6,0 mg/kg day 1 i.v. 60 min

Experimental

FOLFIRI DRUG

Irinotecan 180 mg/m2 day 1 i.v. 30-90 min Folinic acid 400 mg/ m2 day 1 i.v. 120 min 5-FU 400 mg/ m2 day 1 Bolus 5-FU 2.400 mg/ m2 day 1 i.v. 46 hours

Experimental

Eligibility Criteria

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

You may qualify if:

• Competent to understand, sign and date an IEC-approved informed consent form.
• Men or women 18 years of age or older at the time the written informed consent is obtained.
• Obtention of DNA from tumor tissue blocks sent to central lab (ICO) that is amenable for highly sensitive techniques
• Previous irinotecan based chemotherapy +/- bevacizumab for metastatic CCR during at least 6 weeks.
• Disease progression during irinotecan treatment or within 6 months after irinotecan treatment.
• Karnofsky status ≥ 70% .
• Adequate bone marrow, hepatic, renal and metabolic functions,
• Adequate bone marrow function: neutrophils ≥ 1.5x109/ L; platelets ≥ 100x109/L; hemoglobin ≥ 9g/dL.
• Hepatic functions as follows: total bilirubin count ≤ 1.5 x ULN; ALAT and ASAT ≤ 2.5 x ULN (≤ 5 x ULN in case of liver metastasis).
• Renal function: creatinine clearance \> 50 ml/min (according Cockcroft y Gault formulae)
• Metabolic functions: magnesium ≥ lower limit of normal (LIN)
• Life expectancy ≥ 3 months.

You may not qualify if:

• Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma of the skin or pre-invasive cervical cancer.
• Documented or suspected central nervous system metastases.
• Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia.
• Prior anti-EGFr antibody therapy (eg, Cetuximab) or treatment small molecule EGFr tyrosine kinase inhibitors (eg, Erlotinib). Subjects who discontinue their first dose of anti-EGFR therapy (Cetuximab) because of an infusion reaction may participate in this clinical trial.
• Paraffin-embedded tissue or unstained tumor slides from primary or metastatic tumor not available or quality ADN not available for biomarker determination by highly sensitive techniques.
• History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis.
• Acute or sub-acute intestinal occlusion and /or active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as \> 4 loose stools per day).
• History of Gilbert's syndrome or dihydropyrimidine deficiency.
• History of any medical condition that may increase the risks associated with study participation or may interfere with the interpretation of the study results.
• Known positive test for human immunodeficiency virus infection, hepatitis C virus, and chronic active hepatitis B infection.
• Subject allergic to the ingredients of the study medication or to Staphylococcus protein A.
• Any co-morbid disease that would increase risk of toxicity.
• Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures.
• Subject who is pregnant or breast feeding.
• Woman or man of childbearing potential not consenting to use adequate contraceptive precautions.

Sponsors & Collaborators

• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead

Study Sites (1)

Spanish Cooperative Group for Digestive Tumour Therapy

Madrid, 28046, Spain

Location

Related Publications (1)

• Santos C, Azuara D, Vieitez JM, Paez D, Falco E, Elez E, Lopez-Lopez C, Valladares M, Robles-Diaz L, Garcia-Alfonso P, Buges C, Duran G, Salud A, Navarro V, Capella G, Aranda E, Salazar R. Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial. Ann Oncol. 2019 May 1;30(5):796-803. doi: 10.1093/annonc/mdz082.

  PMID: 30840064 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; IFL protocol

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

Study Officials

• Ramón Salazar, MD, PhD

  Institut Català d´Oncologia (ICO) L'Hospitalet

  STUDY CHAIR

• Gabriel Capella

  Institut Català d´Oncologia (ICO) L'Hospitalet

  STUDY CHAIR

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: September 27, 2012
• First Posted: October 11, 2012
• Study Start: October 1, 2012
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: August 1, 2017

Record last verified: 2017-07

Locations

ES (1)