Efficacy of FOLFOX+Bevacizumab in Combination With Irinotecan in the Treatment of Metastatic Colorectal Cancer

Phase 2

Completed

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: 5FU/LV, Oxaliplatin, Bevacizumab, Irinotecan; Drug: Oxaliplatin, 5FU/LV, Bevacizumab

• Registration Number: NCT01321957
• Lead Sponsor: Martin-Luther-Universität Halle-Wittenberg

Brief Summary

The primary objective of this study is to evaluate the efficacy of Irinotecan in combination with FOLFOX+Bevacizumab versus FOLFOX+Bevacizumab alone in the first-line treatment of patients with metastatic colorectal cancer.

Detailed Description

5-Fluorouracil and oxaliplatin (FOLFOX-Regimen) in combination with bevacizumab is regarded as standard first-line treatment in metastatic colorectal cancer \[Saltz et al., 2008\]. Current studies established the role of the FOLFOXIRI regimen \[Souglakos et al., 2006, Falcone et al., 2007\]. A further intensification of the therapy seems feasible yielding response rates up to 84% and a disease control rate up to 100% \[Falcone, 2008, Santomaggio, 2009, Masi, 2010\]. This trial evaluates the activity of an intensified first-line therapy for metastatic colorectal cancer compared to standard treatment.

Study Timeline

• Study First Submitted: 2011-03-23
• Study First Submitted QC: 2011-03-23
• Study First Posted: 2011-03-24
• Study Start: 2011-05
• Primary Completion: 2016-09
• Study Completion: 2018-08-15
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-23
• Last Update Posted: 2018-10-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

1. Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer (primary tumor may be present)

2. Patients with at least one measurable lesion, with size > 1 cm (RECIST v1.1)

3. ECOG Performance status ≤ 2 (ECOG 2, only if tumor related)

4. Patients, who are able to tolerate intensive first lien treatment as judged by the investigator

5. Life expectancy > 3 months

6. Age ≥ 18 years

7. Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x109/L, hemoglobin

   • 9 g/dl or 5.59 mmol/l

8. Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN and aPTT < 1.5 ULN within 7 days prior to registration. The use of full dose anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least two weeks at the time of registration.

9. Adequate liver function as measured by serum transaminases (AST & ALT) ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN) and total bilirubin ≤ 1.5 x ULN

10. Adequate renal function: Serum creatinine ≤ 1.5 x ULN

11. Signed, written informed consent

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Exclusion Criteria

1. Patients with histologically confirmed diagnosis of stage IV (UICC) colorectal cancer (primary tumor may be present)

2. Patients with at least one measurable lesion, with size > 1 cm (RECIST v1.1)

3. ECOG Performance status ≤ 2 (ECOG 2, only if tumor related)

4. Patients, who are able to tolerate intensive first lien treatment as judged by the investigator

5. Life expectancy > 3 months

6. Age ≥ 18 years

7. Haematologic function: ANC ≥ 1.5 x 109/L, platelets ≥ 100 x109/L, hemoglobin

   • 9 g/dl or 5.59 mmol/l

8. Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN and aPTT < 1.5 ULN within 7 days prior to registration. The use of full dose anticoagulants is allowed as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least two weeks at the time of registration.

9. Adequate liver function as measured by serum transaminases (AST & ALT) ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN) and total bilirubin ≤ 1.5 x ULN

10. Adequate renal function: Serum creatinine ≤ 1.5 x ULN

11. Signed, written informed consent

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FOLFOX+Bevacizumab+Irinotecan	5FU/LV, Oxaliplatin, Bevacizumab, Irinotecan	bevacizumab at a dose of 5 mg/kg iv over 30 to 90 min (day 1) irinotecan at a dose of 165 mg/m2 iv over two hours (day 1) oxaliplatin at a dose of 85 mg/m2 iv over two hours (day 1) I-LV at a dose of 200 mg/m2 iv over two hours (day 1) 5-FU at a dose of 3200 mg/ m2 iv over 48 hours (day 1-3)
FOLFOX+Bevacizumab	Oxaliplatin, 5FU/LV, Bevacizumab	bevacizumab at a dose of 5 mg/kg iv over 30 to 90 min (day 1) oxaliplatin at a dose of 85 mg/m2 iv over two hours (day 1) I-LV at a dose of 200 mg/m2 iv over two hours (day 1) 5-FU at a dose of 3200 mg/ m2 iv over 48 hours (day 1-3)

Primary Outcome Measures

Name	Time	Method
progression free survival rate	9 months after first study drug administration

Secondary Outcome Measures

Name	Time	Method
Progression free survival rate	until progression of disease for a maximum of two years after end of treatment
Overall survival	until death for a maximum of two years after end of treatment
Adverse events	18 months after the date of last study drug administration	Toxicity of study medication
Quality of Life evaluated by questionnaire	Until end of treatment (maximum 2 years after first study drug administration)	Quality of Life evaluated using questionnaire EORTC QLQ-30
tumour response according to RECIST v 1.1	until progression of disease for a maximum of two years after end of treatment
Secondary resection rate	for a maximum of two years after end of treatment

Trial Locations

Locations (51)

Klinikum Heidenheim; 🇩🇪 Heidenheim, Germany

Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie; 🇩🇪 Berlin, Germany

Onkologische Praxis; 🇩🇪 Bottrop, Germany

Onkozenrum Dresden; 🇩🇪 Dresden, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Praxis Dr. Schröder; 🇩🇪 Hannover, Germany

Klinikum Region Hannover GmbH,; 🇩🇪 Hannover, Germany

Institut für med. Dokumentation, Gutachtenerstellung, Gesundheitsförderung u. Qualitätssicherung GbR; 🇩🇪 Kaiserslautern, Germany

SP Hämatologie u. Internistische Onkologie; 🇩🇪 Hennigsdorf, Germany

St. Bernward Krankenhaus; 🇩🇪 Hildesheim, Germany

Praxis für Innere Medizin; 🇩🇪 Laatzen, Germany

Gemeinschaftspraxis für Hämatologie und Onkologie; 🇩🇪 Köln, Germany

MVZ Osthessen GmbH; 🇩🇪 Fulda, Germany

Knappschaftskrankenhaus Bottrop; 🇩🇪 Bottrop, Germany

Gemeinschaftspraxis Hämatologie-Onkologie; 🇩🇪 Dresden, Germany

Evangelisches Krankenhhaus Dinslaken; 🇩🇪 Dinslaken, Germany

Städtisches Klinikum Dessau; 🇩🇪 Dessau, Germany

Onkologie Duisburg; 🇩🇪 Duisburg, Germany

Katholisches Krankenhaus St. Johann Nepomuk; 🇩🇪 Erfurt, Germany

St. Georg Klinikum Eisenach gGmbH; 🇩🇪 Eisenach, Germany

pioh Praxis; 🇩🇪 Frechen, Germany

Partnerschaft FÄ für Innere Medizin; 🇩🇪 Freiberg, Germany

Martin-Luther-Universität Halle-Wittenberg; 🇩🇪 Halle/Saale, Germany

Marienkrankenhaus Hamburg; 🇩🇪 Hamburg, Germany

Universitätsklinikum Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Überörtliche Gemeinschaftspraxis für Innere Medizin; 🇩🇪 Hamburg, Germany

Onkologische Schwerpunktpraxis im Medicinum; 🇩🇪 Hildesheim, Germany

Universitätsklinikum Schleswig-Holstein; 🇩🇪 Kiel, Germany

Sanaklinikum Hof GmbH; 🇩🇪 Hof, Germany

St. Cincentius-Kliniken gAG; 🇩🇪 Karlsruhe, Germany

Studiengesellschaft Kátay + Reiser GbR; 🇩🇪 Köln, Germany

Praxis für Innere Medizin und Gastroenterologie; 🇩🇪 Köthen, Germany

Ortenau Klinikum - Lahr Ettenhaim; 🇩🇪 Lahr, Germany

Gemeinschaftspraxis Dr. med. Veling-Kaiser; 🇩🇪 Landshut, Germany

Onco Studies Lörrach-OSL an der Schwerpunktpraxis Onkologie Dreiländereck; 🇩🇪 Lörrach, Germany

Medizinisches Versorgungszentrum Mitte; 🇩🇪 Leipzig, Germany

Klinikum Magdeburg gGmbH; 🇩🇪 Magdeburg, Germany

Universitätsklinikum Magdeburg; 🇩🇪 Magdeburg, Germany

Internistisches Fachzentrum mit Dialyse, Onkologische Praxis am Klinikum; 🇩🇪 Memmingen, Germany

Universitätsklinikum Rostock; 🇩🇪 Rostock, Germany

PIUS-Hospital Oldenburg; 🇩🇪 Oldenburg, Germany

Friedrich-Ebert-Krankenhaus Neumünster GmbH; 🇩🇪 Neumünster, Germany

Praxis für Innere Medizin, Hämatololgie und Onkologie; 🇩🇪 Schkeuditz, Germany

Leopoldina Krankenhaus der Stadt Schweinfurt GmbH; 🇩🇪 Schweinfurt, Germany

MedResearch - Medizinisches Studien- u. Dokumentationszentrum Leipziger Land; 🇩🇪 Rötha, Germany

Praxisnetzwerk Hämaologie/Intern. Onkologie; 🇩🇪 Troisdorf, Germany

Praxis Dr. med. Mathias Schulze; 🇩🇪 Zittau, Germany

Praxisgemeinschaft für Onkologie und Urologie Wilhelmshaven; 🇩🇪 Wilhelmshaven, Germany

Ammerland-Klinik GmbH; 🇩🇪 Westerstede, Germany

Klinikum Mutterhaus der Borromäerinnen gGmbH; 🇩🇪 Trier, Germany

Kreiskrankenhaus Gummersbach GmbH; 🇩🇪 Gummersbach, Germany