Cetuximab Standard or Dose Escalation in First Line Colorectal Cancer

NCT01251536 | Completed Phase 2 Results DMC

• 2 other identifiers: S515322009-009992-36
• Study Type: interventional
• Target: 108
• Locations: 5 countries
• Sites: 30

Brief Summary

The purposes of this study are to determine whether administering escalating doses of cetuximab in patients with no early skin toxicity could delay the progression of disease in a significant proportion of patients and to study the molecular signatures of response.

Conditions

Colorectal Cancer

Keywords

colorectal cancer; K-Ras wildtype; first line metastatic; standard cetuximab + FOLFIRI; dose escalation cetuximab

Outcome Measures

Primary Outcomes (1)

• PFS Probability Rate at 9 Months in the Dose Escalation Arm

  A precise estimate (+/- 10%) of the probability of not having progression at 9 months. This measure is an estimation derived from the Kaplan-Meier algorithm and does not represent a dimple percentage of participants.

  9 months

Secondary Outcomes (17)

• Progression Free Survival (PFS) Median Time

  Treatment + follow-up (3 years from database lock)

• Progression Free Survival (PFS) Median Time for Resected Patients

  Treatment + follow-up (3 years from database lock)

• Progression Free Survival (PFS) Time for Resected Versus Non-resected Patients (Hazard Ratio)

  Treatment + follow-up (3 years from database lock)

• Death Rates by 3 Years Follow-up

  Treatment + follow-up (3 years from database lock)

• Overall Survival (OS) Median Time

  Treatment + follow-up (3 years from database lock)

Study Arms (2)

Arm B - standard dose of cetuximab

OTHER

Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab 250 mg/m2 weekly. No comparison between arms was planned.

Drug: Standard first line treatment with cetuximab + Folfiri

Arm A - dose escalation of cetuximab

EXPERIMENTAL

Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly.

Drug: Dose escalation of cetuximab

Interventions

Dose escalation of cetuximab DRUG

Dose, frequency \& treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly

Also known as: Erbitux

Arm A - dose escalation of cetuximab

Standard first line treatment with cetuximab + Folfiri DRUG

Dose, frequency \& treatment mode: 400 mg/m2 (loading at day 1) followed by 250 mg/m2 weekly (at day 8 and 15) Arm allocation at day 22: Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab: 250 mg/m2 weekly.

Also known as: Erbitux

Arm B - standard dose of cetuximab

Eligibility Criteria

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

You may qualify if:

• Written informed consent (+ optional for PK and TR) must be given according to ICH/GCP and national/local regulations.
• Patient is at least 18 years of age.
• Patient's body weight is ≤ 120 kg.
• Histologically proven and measurable (RECIST criteria v.1.1) metastatic adenocarcinoma of the colon or rectum, not in a previously irradiated area.
• K-Ras wild type tumour eligible for treatment with cetuximab.
• Unresectable metastatic disease.
• Life expectancy of at least 12 weeks.
• WHO ECOG performance status: 0 or 1.
• Effective contraception for both male and female patients if the risk of conception exists.
• Adequate organ function.
• Adequate bone marrow, hepatic and renal function (assessed within 14 days prior to study entry):
• Hemoglobin \> 10.0 g/dL, absolute neutrophil count \> 1.5 x 109/L, platelet count \> 100 x 109/L
• ALAT, ASAT \< 2.5 x ULN, up to \< 5 x ULN in case of liver metastases
• Alkaline phosphatase \< 2.5 x ULN
• Total bilirubin \< 1.5 x ULN

You may not qualify if:

• Prior treatment for metastatic disease (adjuvant therapy with fluoropyrimidines +/-oxaliplatin based regimens allowed if stopped 6 months prior to registration on study).
• Prior treatment with EGFR inhibitor or chemotherapy with irinotecan in adjuvant settings.
• Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry.
• Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment.
• Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy or hormone therapy not indicated in the study protocol.
• Any active dermatological condition \> grade 1.
• Brain metastasis (known or suspected).
• Significant impairment of intestinal absorption (e.g. chronic diarrhea, inflammatory bowel disease).
• Other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection.
• Uncontrolled coronary artery disease and/or unstable angina, a history of a myocardial infarction within the last 12 months or heart failure NYHA class III or IV. High risk of uncontrolled arrhythmia.
• Known allergy or any other adverse reaction to any of the drugs or to any related compound.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Gilbert disease.
• Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin.
• Organ allografts requiring immunosuppressive therapy.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (30)

Universitätsklinik für Innere medizin, Klinishe abteilung für hämatologie und Onkologie

Innsbruck, Austria

Location

LKH Leoben, abteilung f. innere Medizin

Leoben, Austria

Location

AKH Linz, Innere Medizin 3, Zentrum für Hämatologie und medizinishe Onkologie

Linz, Austria

Location

Landeskrankenhaus Salzburg, Univ. Klinik für innere Medizin III, Universitätsklinikum der PMU

Salzburg, Austria

Location

Krankenanstalt Rudolfstiftung, 1 medizinishe Abteilung

Vienna, Austria

Location

St Vincent Krankenhaus Betriebs GmbH

Zams, Austria

Location

Imelda Ziekenhuis

Bonheiden, Belgium

Location

Erasme Hospital

Brussels, 1070, Belgium

Location

Cliniques Universitaires St Luc

Brussels, 1200, Belgium

Location

AZ Middelares Gent

Ghent, Belgium

Location

UZ Gent

Ghent, Belgium

Location

Centre Hospitalier de Jolimont-Lobbes, Oncology Médicale

Haine-Saint-Paul, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

UZ Gasthuisberg

Leuven, 3000, Belgium

Location

CHC Saint Joseph

Liège, Belgium

Location

AZ Sint Maarten Mechelen/Duffel

Mechelen, Belgium

Location

H. Hartziekenhuis

Roeselare, 8800, Belgium

Location

AZ Turnhout (Campus St Elisabeth)

Turnhout, Belgium

Location

Hôpital Avicennes

Bobigny, France

Location

Hôpital Saint-André

Bordeaux, 33000, France

Location

Hopital Européen Georges Pompidou

Paris, 75015, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

CHU Charles Nicolle

Rouen, 76031, France

Location

State Health Center

Budapest, 1062, Hungary

Location

Medical Center of the University of Pecs , National Institute Oncology

Budapest, 1122, Hungary

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Institut Català d'Oncologia

Barcelona, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Clinico Universitario De Valencia

Valencia, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab

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

Limitations and Caveats

Insufficient population in escalation arm A as early skin toxicity in most patients; study not powered for formal comparison between arms. Systematic error sources: some AEs re-coded by sponsor, misclassification bias (local response assessment).

Results Point of Contact

• Title: Prof Dr Eric Van Cutsem
• Organization: UZ Leuven

eric.vancutsem@uzleuven.be

003216344218

Study Officials

• Eric Van Cutsem, MD

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: December 1, 2010
• First Posted: December 2, 2010
• Study Start: December 1, 2010
• Primary Completion: June 1, 2016
• Study Completion: July 1, 2019
• Last Updated: October 11, 2019
• Results First Posted: October 11, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

HU (2); ES (5); AU (6); BE (12); FR (5)