Cap+Bev vs Cap+Iri+Bev 1st-line Therapy in mCRC

Colorectal Cancer Metastatic Clinical Trial

Official title:

Randomized, Open, Multicenter Phase III Study With Capecitabine Plus Bevacizumab Versus Capecitabine Plus Irinotecan Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01249638
• Other study ID #: ML22011
• Status: Recruiting
• Phase: Phase 3
• First received: November 29, 2010
• Last updated: March 11, 2011
• Start date: December 2010
• Est. completion date: December 2016

Study information

• Verified date: November 2010
• Source: Ludwig-Maximilians - University of Munich
• Contact: Volker Heinemann, Prof. Dr.
• Phone: +49 89 7095 0
• Email: volker.heinemann[@]med.uni-muenchen.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

Patient with multiple metastases, not eligible for surgery, might not profit from intensive chemotherapy regimens. Therefore less intensive regimens focusing on survival and disease control may be a better choice for first line treatment. Therefore this study investigates the combination of capecitabine and bevacizumab versus the combination of capecitabine, bevacizumab and irinotecan. In case of progressive disease, the therapy in patients treated with capecitabine and bevacizumab is intensified by adding irinotecan. Primary endpoint is time-of-failure strategy (TFS) comparing both treatment arms.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 516
• Est. completion date: December 2016
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the colon or rectum.

• Stage IV disease.

• ECOG 0-1.

• Patients considered suitable for application of chemotherapy.

• Age 18 - 75 years.

• In- or outpatient treatment.

• Estimated life expectancy > 3 months.

• Measurable index lesion according to RECIST criteria. Evaluation of tumor manifestations = 2 weeks prior to treatment start.

• Effective contraception.

• Adequate hematologic function: leukocytes >= 3000/µl, neutrophils >= 1500/µl, platelets >= 100.000/µ, and hemoglobin >= 9g/dl. Bilirubin <= 1,5x upper limit of normal (ULN). ALAT and ASAT <= 2,5x ULN, in case of liver metastases <= 5x ULN. Serum creatinine <= 1,5x ULN.

• No operations within 4 weeks prior to treatment start. No cytologic biopsies within 1 week prior to treatment start. Operation sequels need to be completely healed. Major operations must not be expected at time of study begin, except for potential secondary resection of liver metastases. In case of secondary resection of liver metastases, bevacizumab must be discontinued 6-8 weeks prior to surgery.

• No relevant toxicities due to prior medical treatment at time of study entry.

Exclusion Criteria:

• primary resectable metastases

• heart failure Grade III/IV (NYHA-classification)

• Prior treatment directed against the epidermal growth factor receptor (EGFR).

• Prior treatment with bevacizumab.

• Prior chemotherapy for colorectal cancer, except for adjuvant chemotherapy dating back > 6 months prior to study entry.

• Experimental medical treatment within 30 days prior to study entry.

• Known hypersensitivity reaction to any study medication.

• Pregnant or breast feeding women (pregnancy needs to be excluded by testing of beta-HCG).

• Known or suspected cerebral metastases.

• Clinically significant coronary heart disease, myocardial infarction within the last 12 months or high risk of uncontrolled arrhythmia.

• Acute or subacute ileus, chronic inflammatory bowel disease or chronic diarrhea.

• Abdominal or tracheo-esophageal fistulas, gastrointestinal perforation within 6 months before study entry

• Symptomatic peritoneal carcinosis.

• Severe chronic wounds, ulcera or bone fracture.

• Uncontrolled hypertension.

• Severe proteinuria (nephrotic syndrome).

• Arterial thromboembolic events or hemorrhage within 6 months prior to study entry (except tumor bleeding surgically treated by tumor resection).

• Bleeding diatheses or coagulopathy.

• Full dose anticoagulation.

• Known DPD-deficiency (special screening not required).

• Known glucuronidation-deficiency (special screening not required).

• Contraindication with irinotecan

• Medical history of other malignant disease within 5 years prior to study entry, except for basalioma, and in-situ cervical carcinoma if treated with curative intent.

• Known alcohol or drug abuse.

• Medical or psychiatric condition which contradicts participation of study.

• Limited legal capacity.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer Metastatic
• Colorectal Neoplasms

Intervention

Drug:
• Capecitabine
Capecitabine:2 x 1250 mg/m2 day 1-14 followed by 1 week pause q day 21
• Bevacizumab
Bevacizumab: 7.5 mg/kg day 1 q day 21
• Capecitabine
Capecitabine: 2 x 800mg/m2 day 1-14 followed by 1 week pause q day 21
• Irinotecan
Irinotecan: 200 mg/m2 day 1 , q day 21
• Bevacizumab
Bevacizumab: 7.5 mg/kg day 1, q day 21

Locations

Country	Name	City	State
Germany	University of Munich - Klinikum der Universitaet Muenchen	Munich

Sponsors (2)

Lead Sponsor	Collaborator
Ludwig-Maximilians - University of Munich	Roche Pharma AG

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TFS	Time of Failure Strategy	9 months	Yes
Secondary	ORR, OS, Quality of Life, PFS-1		36 months	Yes