Clinical trial NCT01321957: Efficacy of FOLFOX+Bevacizumab in Combination With Irinotecan in the Treatment of Metastatic Colorectal Cancer
Official title: FOLFOX and Bevacizumab With or Without Irinotecan in First-line Treatment for Metastatic Colorectal Cancer. A Randomized Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Martin-Luther-Universität Halle-Wittenberg
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2011-03-24
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: progression free survival rate
timeFrame: 9 months after first study drug administration
Secondary outcomes:
measure: tumour response according to RECIST v 1.1
timeFrame: until progression of disease for a maximum of two years after end of treatment
measure: Secondary resection rate
timeFrame: for a maximum of two years after end of treatment
measure: Progression free survival rate
timeFrame: until progression of disease for a maximum of two years after end of treatment
measure: Overall survival
timeFrame: until death for a maximum of two years after end of treatment
measure: Adverse events
timeFrame: 18 months after the date of last study drug administration
measure: Quality of Life evaluated by questionnaire
timeFrame: Until end of treatment (maximum 2 years after first study drug administration)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Medizinische Klinik mit Schwerpunkt Hämatologie und Onkologie
city: Bottrop
country: Germany
facility: Knappschaftskrankenhaus Bottrop
city: Bottrop
country: Germany
facility: Onkologische Praxis
city: Dessau
country: Germany
facility: Städtisches Klinikum Dessau
city: Dinslaken
country: Germany
facility: Evangelisches Krankenhhaus Dinslaken
city: Dresden
country: Germany
facility: Gemeinschaftspraxis Hämatologie-Onkologie
city: Dresden
country: Germany
facility: Onkozenrum Dresden
city: Duisburg
country: Germany
facility: Onkologie Duisburg
city: Eisenach
country: Germany
facility: St. Georg Klinikum Eisenach gGmbH
city: Erfurt
country: Germany
facility: Katholisches Krankenhaus St. Johann Nepomuk
city: Frechen
country: Germany
facility: pioh Praxis
city: Freiberg
country: Germany
facility: Partnerschaft FÄ für Innere Medizin
city: Fulda
country: Germany
facility: MVZ Osthessen GmbH
city: Gummersbach
country: Germany
facility: Kreiskrankenhaus Gummersbach GmbH
city: Halle/Saale
country: Germany
facility: Martin-Luther-Universität Halle-Wittenberg
city: Hamburg
country: Germany
facility: Marienkrankenhaus Hamburg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Überörtliche Gemeinschaftspraxis für Innere Medizin
city: Hannover
country: Germany
facility: Klinikum Region Hannover GmbH,
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Hannover
country: Germany
facility: Praxis Dr. Schröder
city: Heidenheim
country: Germany
facility: Klinikum Heidenheim
city: Hennigsdorf
country: Germany
facility: SP Hämatologie u. Internistische Onkologie
city: Hildesheim
country: Germany
facility: Onkologische Schwerpunktpraxis im Medicinum
city: Hildesheim
country: Germany
facility: St. Bernward Krankenhaus
city: Hof
country: Germany
facility: Sanaklinikum Hof GmbH
city: Kaiserslautern
country: Germany
facility: Institut für med. Dokumentation, Gutachtenerstellung, Gesundheitsförderung u. Qualitätssicherung GbR
city: Karlsruhe
country: Germany
facility: St. Cincentius-Kliniken gAG
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Köln
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Onkologie
city: Köln
country: Germany
facility: Studiengesellschaft Kátay + Reiser GbR
city: Köthen
country: Germany
facility: Praxis für Innere Medizin und Gastroenterologie
city: Laatzen
country: Germany
facility: Praxis für Innere Medizin
city: Lahr
country: Germany
facility: Ortenau Klinikum - Lahr Ettenhaim
city: Landshut
country: Germany
facility: Gemeinschaftspraxis Dr. med. Veling-Kaiser
city: Leipzig
country: Germany
facility: Medizinisches Versorgungszentrum Mitte
city: Lörrach
country: Germany
facility: Onco Studies Lörrach-OSL an der Schwerpunktpraxis Onkologie Dreiländereck
city: Magdeburg
country: Germany
facility: Klinikum Magdeburg gGmbH
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg
city: Memmingen
country: Germany
facility: Internistisches Fachzentrum mit Dialyse, Onkologische Praxis am Klinikum
city: Neumünster
country: Germany
facility: Friedrich-Ebert-Krankenhaus Neumünster GmbH
city: Oldenburg
country: Germany
facility: PIUS-Hospital Oldenburg
city: Rostock
country: Germany
facility: Universitätsklinikum Rostock
city: Rötha
country: Germany
facility: MedResearch - Medizinisches Studien- u. Dokumentationszentrum Leipziger Land
city: Schkeuditz
country: Germany
facility: Praxis für Innere Medizin, Hämatololgie und Onkologie
city: Schweinfurt
country: Germany
facility: Leopoldina Krankenhaus der Stadt Schweinfurt GmbH
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromäerinnen gGmbH
city: Troisdorf
country: Germany
facility: Praxisnetzwerk Hämaologie/Intern. Onkologie
city: Westerstede
country: Germany
facility: Ammerland-Klinik GmbH
city: Wilhelmshaven
country: Germany
facility: Praxisgemeinschaft für Onkologie und Urologie Wilhelmshaven
city: Zittau
country: Germany
facility: Praxis Dr. med. Mathias Schulze
Study officials:
affiliation: Universitätsklinikum Halle
name: Hans-Joachim Schmoll, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.