Dual Targeting of EGFR With Cetuximab and Afatinib to Treat Refractory wtKRAS Metastatic Colorectal Cancer

NCT01919879 | Completed Phase 2 DMC

• 1 other identifier: UCGI 25
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicentric, phase II and open label study.75 patients are expected to be randomized in 35 centers. The main objective is to assess the efficacy and safety of Afatinib -cetuximab combo versus cetuximab alone in treatment of patients with refractory wtKRAS metastatic colorectal cancer.

Conditions

Metastatic Colorectal Cancer

Keywords

Chemotherapy refractory; wtKRAS metastatic colorectal cancer; cross over

Outcome Measures

Primary Outcomes (1)

• Non progression rate at 6 months

  The progression rate is defined as percentage of patients without progression at 6 months after observation of all patients at 6 months

  6 months

Secondary Outcomes (5)

• Overall response rate (OR)

  6 months

• Progression free survival

  until progression or death, expected average approximately 4 months

• Overall and specific survival

  until death, on average approximately 14 months

• Quality of life

  During treatment, on average approximately 4 months

• Tolerance of the treatment

  until progression, expected approximately 4 months

Study Arms (2)

Arm A: Cetuximab + Afatinib

EXPERIMENTAL

Afatinib 40 mg daily Cetuximab 500 mg/m2 every 2 weeks until progression

Drug: Cetuximab + Afatinib

Arm B : Cetuximab alone

ACTIVE COMPARATOR

Cetuximab 500mg/m2 every 2 weeks until progression After progression: Cetuximab 500mg/m2 + Afatinib 40 mg per day until progression

Drug: Cetuximab + Afatinib; Drug: Cetuximab

Interventions

Cetuximab + Afatinib DRUG

Afatinib taken orally, cetuximab administered intravenously

Also known as: Erbitux

Arm A: Cetuximab + Afatinib; Arm B : Cetuximab alone

Cetuximab DRUG

Cetuximab administered intravenously

Also known as: Erbitux

Arm B : Cetuximab alone

Eligibility Criteria

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

You may qualify if:

• Metastatic colorectal cancer expressing the wtKRAS status
• No previous EGFR targeted therapy.
• Must have failed a prior regimen containing irinotecan for metastatic disease and a prior regimen containing oxaliplatin for metastatic disease
• Must have previously received a thymidylate synthase inhibitor (eg, fluorouracil, capecitabine, raltitrexed, or fluorouracil-uracil) at any point for treatment of colorectal cancer (CRC)
• Life expectancy of at least 3 months.
• Patient with ECOG ≤ 1
• Patients aged ≥ 18.
• Patient with measurable lesions according to RECIST criteria (version 1.1) with spiral CT scan and defined as ≥ 10 mm in longest diameter and 2X the slice thickness for extra nodal lesions and/or \> 15 mm in short axis diameter for nodal lesions
• Patient able to receive adequate oral nutrition of ≥ 1500 calories per day and free of significant nausea and vomiting
• Patient with adequate organ function:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Haemoglobin ≥ 9 g/dL
• Platelets (PTL) ≥ 100 x 109/L
• AST/ALT ≤ 3 x ULN (≤ 5 x ULN in case of liver metastases)
• GammaGT \< 3 x ULN (\< 5 x ULN in case of liver involvement)

You may not qualify if:

• Previous EGFR targeted therapy.
• Mutant KRAS status
• Prior severe reaction to a monoclonal antibody
• No heart failure or coronary heart disease symptoms Clinically relevant cardiovascular abnormalities, as judged by the investigator, such as, but not limited to, uncontrolled hypertension, congestive heart failure NYHA classification \> III, unstable angina, myocardial infarction within six months prior to randomisation, or poorly controlled arrhythmia
• Cardiac left ventricular dysfunction with resting ejection fraction of less than institutional lower limit of normal (if no lower limit of normal is defined in the institution, the lower limit is 50%)
• Symptomatic brain metastases requiring treatment
• Major surgery within 28 days or minor surgery within 14 days of the start of the study treatment
• Radiotherapy less than two weeks prior to the start of the study treatment
• Systemic chemotherapy, hormonal therapy, immunotherapy ≤ 21 days before study treatment
• No major comorbidity that may preclude the delivery of treatment or active infection (HIV or chronic hepatitis B or C) or uncontrolled diabetes.
• Concomitant occurrence of another cancer, or history of cancer within the past five years except in situ carcinoma of the cervix treated or basal cell carcinoma or squamous cell carcinoma.
• Known pre-existing interstitial lung disease
• Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn's disease, malabsorption, or CTCAE grade \>2 diarrhea of any etiology
• Pregnant woman or lactating woman.
• Persons deprived of liberty or under guardianship.

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (1)

Institute de Cancérologie de la Loire

Nantes, 44805, France

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Afatinib

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; Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Helene SENELLART, Dr

  Centre René Gauducheau- Nantes Saint herbelain

  PRINCIPAL INVESTIGATOR

• Evelyne BOUCHER, Dr

  Centre Eugène Marquis-Rennes

  PRINCIPAL INVESTIGATOR

• Eric FRANCOIS, Dr

  Centre Antoine Lacassagne, Nice

  PRINCIPAL INVESTIGATOR

• Emmanuelle SAMALIN SCALZI, Dr

  Centre Val d'Aurel-Paul Lamarque-Montpellier

  PRINCIPAL INVESTIGATOR

• Meher BEN ABDELGHANI, Dr

  Centre Paul Strauss-Strasbourg

  PRINCIPAL INVESTIGATOR

• Antoine ADENIS, Pr

  Centre Oscar Lambret_Lille

  PRINCIPAL INVESTIGATOR

• Christelle DE LA FOUCHARDIERE, Dr

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

• François GHIRENGHELLI, Dr

  Centre Georges Leclerc-Dijon

  PRINCIPAL INVESTIGATOR

• Olivier DUBROEUCQ, Dr

  Centre Jean Godinot-Reims

  PRINCIPAL INVESTIGATOR

• Emmanuelle MITRY, Dr

  Hopital Rene Huguenin_Intitut Curie_Paris

  PRINCIPAL INVESTIGATOR

• Christophe BORG, Pr

  Hôpital Jean Minjoz-Besaçon

  PRINCIPAL INVESTIGATOR

• Yves BOUCARN, Dr

  Institut Bergonié Bordeaux

  PRINCIPAL INVESTIGATOR

• Christophe BORG, Pr

  Centre Hospitalier de Belfort-Montbelliard

  PRINCIPAL INVESTIGATOR

• Marion CHAUVENET, Dr

  Centre Hospitalier Lyon Sud-Pierre Benite

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 1, 2013
• First Posted: August 9, 2013
• Study Start: October 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: December 1, 2017
• Last Updated: May 8, 2018

Record last verified: 2018-05

Locations

FR (1)