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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2010 by Ludwig-Maximilians - University of Munich
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by:
Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier:
NCT01249638
First received: November 29, 2010
Last updated: March 11, 2011
Last verified: November 2010
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer Metastatic
Drug: Capecitabine
Drug: Bevacizumab
Drug: Irinotecan
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Ludwig-Maximilians - University of Munich:

Primary Outcome Measures:
  • TFS [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    Time of Failure Strategy


Secondary Outcome Measures:
  • ORR, OS, Quality of Life, PFS-1 [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 516
Study Start Date: December 2010
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cap+Bev until PD followed by CAPIRI +Bev

Capecitabine + Bevacizumab

In case of Progression Escalation to:

Capecitabine + Irinotecan + Bevacizumab

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01249638

Contacts
Contact: Volker Heinemann, Prof. Dr. +49 89 7095 0 volker.heinemann@med.uni-muenchen.de

Locations
Germany
University of Munich - Klinikum der Universitaet Muenchen Recruiting
Munich, Germany, 81377
Contact: Volker Heinemann, Prof. Dr. med.    +49 89 7095 0    volker.heinemann@med.uni-muenchen.de   
Contact: Clemens Giesse, Dr. med.    +49 89 7095 0    clemens.giessen@med.uni-muenchen.de   
Principal Investigator: Volker Heinemann, Prof. Dr. med.         
Sub-Investigator: Clemens Giessen, Dr. med.         
Sponsors and Collaborators
Ludwig-Maximilians - University of Munich
Roche Pharma AG
Investigators
Principal Investigator: Volker Heinemann, Prof. Dr. med. University of Munich - Klinikum der Universitaet Muenchen
Study Chair: Sebastian Stintzing, Dr. med. University of Munich - Klinikum der Universitaet Muenchen
Study Chair: Clemens Giessen University of Munich - Klinikum der Universitaet Muenchen
  More Information

No publications provided by Ludwig-Maximilians - University of Munich

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Volker Heinemann, Prof. Dr. med., University of Munich - Klinikum der Universitaet Muenchen
ClinicalTrials.gov Identifier: NCT01249638     History of Changes
Other Study ID Numbers: ML22011
Study First Received: November 29, 2010
Last Updated: March 11, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ludwig-Maximilians - University of Munich:
Bevacizumab
Capecitabine
Irinotecan
mCRC

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Capecitabine
Fluorouracil
Irinotecan
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 20, 2014