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

NCT01249638 | Unknown Phase 3 DMC

• 1 other identifier: ML22011
• Study Type: interventional
• Target: 516
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer Metastatic

Keywords

Bevacizumab; Capecitabine; Irinotecan; mCRC

Outcome Measures

Primary Outcomes (1)

• TFS

  Time of Failure Strategy

  9 months

Secondary Outcomes (1)

• ORR, OS, Quality of Life, PFS-1

  36 months

Study Arms (2)

Cap+Bev until PD followed by CAPIRI +Bev

EXPERIMENTAL

Capecitabine + Bevacizumab In case of Progression Escalation to: Capecitabine + Irinotecan + Bevacizumab

Drug: Capecitabine; Drug: Bevacizumab

Capiri + Bev

ACTIVE COMPARATOR

Capecitabine + Irinotecan + Bevacizumab

Drug: Capecitabine; Drug: Irinotecan; Drug: Bevacizumab

Interventions

Capecitabine DRUG

Capecitabine:2 x 1250 mg/m2 day 1-14 followed by 1 week pause q day 21

Cap+Bev until PD followed by CAPIRI +Bev

Bevacizumab DRUG

Bevacizumab: 7.5 mg/kg day 1 q day 21

Cap+Bev until PD followed by CAPIRI +Bev

Irinotecan DRUG

Irinotecan: 200 mg/m2 day 1 , q day 21

Capiri + Bev

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead
• Roche Pharma AG: collaborator

Study Sites (1)

University of Munich - Klinikum der Universitaet Muenchen

Munich, 81377, Germany

RECRUITING

Related Publications (6)

• Stahler A, Modest DP, Stintzing S, Borelli B, Keller T, Held S, Fischer von Weikersthal L, Muller L, Graeven U, Decker T, Heintges T, Kahl C, Hoppe B, Kiani A, Kaiser F, Schwaner I, Fruehauf S, Karthaus M, Trarbach T, Klauschen F, Horst D, Cremolini C, Heinemann V. Individual Patient Data Meta-Analysis of Consensus Molecular Subtypes as Biomarkers of First-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer. J Clin Oncol. 2026 Jan;44(1):31-41. doi: 10.1200/JCO-25-00596. Epub 2025 Nov 18.

  PMID: 41252656 DERIVED

• Stahler A, Modest DP, Fischer von Weikersthal L, Kaiser F, Decker T, Held S, Graeven U, Schwaner I, Denzlinger C, Schenk M, Kurreck A, Heinrich K, Giessen-Jung C, Neumann J, Kirchner T, Jung A, Stintzing S, Heinemann V. First-line fluoropyrimidine plus bevacizumab followed by irinotecan-escalation versus initial fluoropyrimidine, irinotecan and bevacizumab in patients with metastatic colorectal cancer - Final survival and per-protocol analysis of the randomised XELAVIRI trial (AIO KRK 0110). Eur J Cancer. 2022 Sep;173:194-203. doi: 10.1016/j.ejca.2022.06.019. Epub 2022 Aug 5.

  PMID: 35940054 DERIVED

• Stahler A, Heinemann V, Schuster V, Heinrich K, Kurreck A, Giessen-Jung C, Fischer von Weikersthal L, Kaiser F, Decker T, Held S, Graeven U, Schwaner I, Denzlinger C, Schenk M, Neumann J, Kirchner T, Jung A, Kumbrink J, Stintzing S, Modest DP. Consensus molecular subtypes in metastatic colorectal cancer treated with sequential versus combined fluoropyrimidine, bevacizumab and irinotecan (XELAVIRI trial). Eur J Cancer. 2021 Nov;157:71-80. doi: 10.1016/j.ejca.2021.08.017. Epub 2021 Sep 8.

  PMID: 34507244 DERIVED

• Heinrich K, Modest DP, Ricard I, Fischer von Weikersthal L, Decker T, Kaiser F, Graeven U, Uhlig J, Schenk M, Freiberg-Richter J, Peuser B, Denzlinger C, Giessen-Jung C, Stahler A, Michl M, Held S, Jung A, Kirchner T, Stintzing S, Heinemann V. Gender-dependent survival benefit from first-line irinotecan in metastatic colorectal cancer. Subgroup analysis of a phase III trial (XELAVIRI-study, AIO-KRK-0110). Eur J Cancer. 2021 Apr;147:128-139. doi: 10.1016/j.ejca.2021.01.025. Epub 2021 Feb 27.

  PMID: 33647548 DERIVED

• Modest DP, Fischer von Weikersthal L, Decker T, Vehling-Kaiser U, Uhlig J, Schenk M, Freiberg-Richter J, Peuser B, Denzlinger C, Peveling Genannt Reddemann C, Graeven U, Schuch G, Schwaner I, Stahler A, Jung A, Kirchner T, Held S, Stintzing S, Giessen-Jung C, Heinemann V; XELAVIRI/AIO KRK0110 Investigators. Sequential Versus Combination Therapy of Metastatic Colorectal Cancer Using Fluoropyrimidines, Irinotecan, and Bevacizumab: A Randomized, Controlled Study-XELAVIRI (AIO KRK0110). J Clin Oncol. 2019 Jan 1;37(1):22-32. doi: 10.1200/JCO.18.00052. Epub 2018 Nov 2.

  PMID: 30388045 DERIVED

• Giessen C, von Weikersthal LF, Hinke A, Stintzing S, Kullmann F, Vehling-Kaiser U, Mayerle J, Bangerter M, Denzlinger C, Sieber M, Teschendorf C, Freiberg-Richter J, Schulz C, Modest DP, Moosmann N, Aubele P, Heinemann V. A randomized, phase III trial of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in first-line treatment of metastatic colorectal cancer: the AIO KRK 0110 trial/ML22011 trial. BMC Cancer. 2011 Aug 23;11:367. doi: 10.1186/1471-2407-11-367.

  PMID: 21861888 DERIVED

MeSH Terms

Interventions

Capecitabine; Bevacizumab; Irinotecan

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids

Study Officials

• Volker Heinemann, Prof. Dr. med.

  University of Munich - Klinikum der Universitaet Muenchen

  PRINCIPAL INVESTIGATOR

• Sebastian Stintzing, Dr. med.

  University of Munich - Klinikum der Universitaet Muenchen

  STUDY CHAIR

• Clemens Giessen

  University of Munich - Klinikum der Universitaet Muenchen

  STUDY CHAIR

Central Study Contacts

Volker Heinemann, Prof. Dr.

CONTACT

+49 89 7095 0; volker.heinemann@med.uni-muenchen.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 29, 2010
• First Posted: November 30, 2010
• Study Start: December 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2016
• Last Updated: March 14, 2011

Record last verified: 2010-11

Locations

DE (1)