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

Metastatic Colorectal Cancer Clinical Trial

— CHARTA  

Official title:

FOLFOX and Bevacizumab With or Without Irinotecan in First-line Treatment for Metastatic Colorectal Cancer. A Randomized Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01321957
• Other study ID #: AIO-0209
• Status: Completed
• Phase: Phase 2
• Start date: May 2011
• Est. completion date: August 15, 2018

Study information

• Verified date: October 2018
• Source: Martin-Luther-Universität Halle-Wittenberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: August 15, 2018
• Est. primary completion date: September 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• 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)
• 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)

Locations

Country	Name	City	State
Germany	Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie	Berlin
Germany	Knappschaftskrankenhaus Bottrop	Bottrop
Germany	Onkologische Praxis	Bottrop
Germany	Städtisches Klinikum Dessau	Dessau
Germany	Evangelisches Krankenhhaus Dinslaken	Dinslaken
Germany	Gemeinschaftspraxis Hämatologie-Onkologie	Dresden
Germany	Onkozenrum Dresden	Dresden
Germany	Onkologie Duisburg	Duisburg
Germany	St. Georg Klinikum Eisenach gGmbH	Eisenach
Germany	Katholisches Krankenhaus St. Johann Nepomuk	Erfurt
Germany	pioh Praxis	Frechen
Germany	Partnerschaft FÄ für Innere Medizin	Freiberg
Germany	MVZ Osthessen GmbH	Fulda
Germany	Kreiskrankenhaus Gummersbach GmbH	Gummersbach
Germany	Martin-Luther-Universität Halle-Wittenberg	Halle/Saale
Germany	Marienkrankenhaus Hamburg	Hamburg
Germany	Überörtliche Gemeinschaftspraxis für Innere Medizin	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Klinikum Region Hannover GmbH,	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Praxis Dr. Schröder	Hannover
Germany	Klinikum Heidenheim	Heidenheim
Germany	SP Hämatologie u. Internistische Onkologie	Hennigsdorf
Germany	Onkologische Schwerpunktpraxis im Medicinum	Hildesheim
Germany	St. Bernward Krankenhaus	Hildesheim
Germany	Sanaklinikum Hof GmbH	Hof
Germany	Institut für med. Dokumentation, Gutachtenerstellung, Gesundheitsförderung u. Qualitätssicherung GbR	Kaiserslautern
Germany	St. Cincentius-Kliniken gAG	Karlsruhe
Germany	Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Gemeinschaftspraxis für Hämatologie und Onkologie	Köln
Germany	Studiengesellschaft Kátay + Reiser GbR	Köln
Germany	Praxis für Innere Medizin und Gastroenterologie	Köthen
Germany	Praxis für Innere Medizin	Laatzen
Germany	Ortenau Klinikum - Lahr Ettenhaim	Lahr
Germany	Gemeinschaftspraxis Dr. med. Veling-Kaiser	Landshut
Germany	Medizinisches Versorgungszentrum Mitte	Leipzig
Germany	Onco Studies Lörrach-OSL an der Schwerpunktpraxis Onkologie Dreiländereck	Lörrach
Germany	Klinikum Magdeburg gGmbH	Magdeburg
Germany	Universitätsklinikum Magdeburg	Magdeburg
Germany	Internistisches Fachzentrum mit Dialyse, Onkologische Praxis am Klinikum	Memmingen
Germany	Friedrich-Ebert-Krankenhaus Neumünster GmbH	Neumünster
Germany	PIUS-Hospital Oldenburg	Oldenburg
Germany	Universitätsklinikum Rostock	Rostock
Germany	MedResearch - Medizinisches Studien- u. Dokumentationszentrum Leipziger Land	Rötha
Germany	Praxis für Innere Medizin, Hämatololgie und Onkologie	Schkeuditz
Germany	Leopoldina Krankenhaus der Stadt Schweinfurt GmbH	Schweinfurt
Germany	Klinikum Mutterhaus der Borromäerinnen gGmbH	Trier
Germany	Praxisnetzwerk Hämaologie/Intern. Onkologie	Troisdorf
Germany	Ammerland-Klinik GmbH	Westerstede
Germany	Praxisgemeinschaft für Onkologie und Urologie Wilhelmshaven	Wilhelmshaven
Germany	Praxis Dr. med. Mathias Schulze	Zittau

Sponsors (2)

Lead Sponsor	Collaborator
Martin-Luther-Universität Halle-Wittenberg	Roche Pharma AG

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression free survival rate		9 months after first study drug administration
Secondary	tumour response according to RECIST v 1.1		until progression of disease for a maximum of two years after end of treatment
Secondary	Secondary resection rate		for a maximum of two years after end of treatment
Secondary	Progression free survival rate		until progression of disease for a maximum of two years after end of treatment
Secondary	Overall survival		until death for a maximum of two years after end of treatment
Secondary	Adverse events	Toxicity of study medication	18 months after the date of last study drug administration
Secondary	Quality of Life evaluated by questionnaire	Quality of Life evaluated using questionnaire EORTC QLQ-30	Until end of treatment (maximum 2 years after first study drug administration)