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

NCT ID: NCT01321957

Last Updated: 2018-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2018-08-15

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FOLFOX+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)

Group Type: ACTIVE_COMPARATOR

Oxaliplatin, 5FU/LV, Bevacizumab

Intervention Type: DRUG

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)

FOLFOX+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)

Group Type: EXPERIMENTAL

5FU/LV, Oxaliplatin, Bevacizumab, Irinotecan

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: DRUG

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)

Intervention Type: DRUG

Other Intervention Names

Bevacizumab; Oxaliplatin; I-LV; 5-FU; Bevacizumab; Oxaliplatin; I-LV; 5-FU; Irinotecan

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Martin-Luther-Universität Halle-Wittenberg

OTHER

Sponsor Role: lead

Responsible Party

Hans-Joachim Schmoll, MD

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hans-Joachim Schmoll, MD

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinikum Halle

Locations

Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie

Berlin, , Germany

Knappschaftskrankenhaus Bottrop

Bottrop, , Germany

Onkologische Praxis

Bottrop, , Germany

Gemeinschaftspraxis für Hämatologie und Onkologie

Cologne, , Germany

Studiengesellschaft Kátay + Reiser GbR

Cologne, , 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, , Germany

Marienkrankenhaus Hamburg

Hamburg, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Überörtliche Gemeinschaftspraxis für Innere Medizin

Hamburg, , Germany

Klinikum Region Hannover GmbH,

Hanover, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Praxis Dr. Schröder

Hanover, , 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

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

Loerrach, , 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, , Germany

Countries

Germany

References

Schmoll HJ, Mann J, Meinert F, Garlipp B, Borchert K, Vogel A, Goekkurt E, Kaiser U, Hoeffkes HG, Russel J, Kanzler S, Edelmann T, Forstbauer H, Gohler T, Hannig C, Hildebrandt B, Roll C, Bokemeyer C, Steighardt J, Cygon F, Ibach S, Stein A, Tintelnot J. Efficacy and quality of life for FOLFOX/bevacizumab +/- irinotecan in first-line metastatic colorectal cancer-final results of the AIO CHARTA trial. Br J Cancer. 2024 Feb;130(2):233-241. doi: 10.1038/s41416-023-02496-4. Epub 2023 Nov 23.

Reference Type: DERIVED

PMID: 37996507 (View on PubMed)

Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.

Reference Type: DERIVED

PMID: 32816630 (View on PubMed)

Stein A, Glockzin G, Wienke A, Arnold D, Edelmann T, Hildebrandt B, Hollerbach S, Illerhaus G, Konigsrainer A, Richter M, Schlitt HJ, Schmoll HJ. Treatment with bevacizumab and FOLFOXIRI in patients with advanced colorectal cancer: presentation of two novel trials (CHARTA and PERIMAX) and review of the literature. BMC Cancer. 2012 Aug 16;12:356. doi: 10.1186/1471-2407-12-356.

Reference Type: DERIVED

PMID: 22897915 (View on PubMed)

Other Identifiers

AIO-0209

Identifier Type: -

Identifier Source: org_study_id