Optimal Maintenance Therapy With Bevacizumab After Induction in Metastatic Colorectal Cancer (CRC)

NCT00973609 | Completed Phase 3 DMC

• 3 other identifiers: AIO-KRK-0207ML21768EudraCT-Nr.: 2008-007974-39
• Study Type: interventional
• Target: 853
• Locations: 1 country
• Sites: 1

Brief Summary

Investigating the efficacy of maintenance and reinduction treatment or no treatment and watchful waiting in subjects with inoperable or irresectable and non-progressive metastatic colorectal cancer after first line induction treatment for 24 weeks with a fluoropyrimidine-, oxaliplatin- and bevacizumab-based chemotherapy. The maintenance treatment with capecitabine or 5-FU/folinic acid and bevacizumab will be compared with a maintenance treatment with bevacizumab alone or no maintenance treatment. Reinduction treatment will be done in case of progression.

Conditions

Colorectal Neoplasms

Keywords

metastatic colorectal cancer; Bevacizumab; Avastin®; phase 3; maintenance treatment; treatment pause; drug holiday; stage IV

Outcome Measures

Primary Outcomes (1)

• Time to failure of maintenance and reinduction treatment strategy measured from randomization

  From randomization until second progression after reinduction treatment

Secondary Outcomes (1)

• TFS, Toxicity, QoL, PFS 1, PFS 2, ORR (first induction), ORR (reind. treatm.), Treatment free interval/duration of maintenance therapy, second. Resection rate, Reasons for discontinuation, OS, Translational research.

  From enrollment until second progression after reinduction treatment

Study Arms (3)

Fluoropyrimidine + Bevacizumab

ACTIVE COMPARATOR

Standard therapy

Drug: 5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab

Bevacizumab monotherapy

EXPERIMENTAL

Drug: 5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab

No maintenance treatment

EXPERIMENTAL

Drug: 5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab

Interventions

5-Fluorouracil, Folic acid, Capecitabine; Bevacizumab DRUG

Induction (and reinduction) treatment regimen for 24 weeks: Fluoropyrimidine, oxaliplatin and bevacizumab. Following induction treatment regimen (for maintenance treatment): No maintenance treatment.

No maintenance treatment

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed and inoperable or irresectable metastatic colorectal cancer (stage IV)
• Measurable lesion according to RECIST measured within 4 weeks prior to registration of the subject for the study
• Not allowed prior treatments:
• Previous chemotherapy for metastatic disease (adjuvant therapy for non-metastasized disease is allowed if terminated more than 6 months ago and without recurrence within 6 months after the end of adjuvant treatment)
• Prior radiation of indicator lesion(s), except for documented progression during radiation and termination of radiotherapy at least 4 weeks prior to entry into the study
• and over
• ECOG 0-2
• Prior and concomitant associated diseases:
• No past or current history of malignancies except for the indication under this study and curatively treated:
• Basal and squamous cell carcinoma of the skin
• in situ carcinoma of the cervix
• Other malignant disease without recurrence after at least 5 years of follow-up
• No history or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumour, seizure not controlled with standard medical therapy, brain metastases or history of stroke).
• No pre-existing neuropathy \> = grade 1 (NCI CTCAE), except for loss of tendon reflex as the only symptom
• No interstitial pneumonia or symptomatic fibrosis of the lung

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Roche Pharma AG: collaborator

Study Sites (1)

AIO-Studien gGmbH

Berlin, State of Berlin, 10623, Germany

Location

Related Publications (4)

• Lueong SS, Herbst A, Liffers ST, Bielefeld N, Horn PA, Tannapfel A, Reinacher-Schick A, Hinke A, Hegewisch-Becker S, Kolligs FT, Siveke JT. Serial Circulating Tumor DNA Mutational Status in Patients with KRAS-Mutant Metastatic Colorectal Cancer from the Phase 3 AIO KRK0207 Trial. Clin Chem. 2020 Dec 1;66(12):1510-1520. doi: 10.1093/clinchem/hvaa223.

  PMID: 33257977 DERIVED

• Hegewisch-Becker S, Nopel-Dunnebacke S, Hinke A, Graeven U, Reinacher-Schick A, Hertel J, Lerchenmuller CA, Killing B, Depenbusch R, Al-Batran SE, Lange T, Dietrich G, Tannapfel A, Arnold D. Impact of primary tumour location and RAS/BRAF mutational status in metastatic colorectal cancer treated with first-line regimens containing oxaliplatin and bevacizumab: Prognostic factors from the AIO KRK0207 first-line and maintenance therapy trial. Eur J Cancer. 2018 Sep;101:105-113. doi: 10.1016/j.ejca.2018.06.015. Epub 2018 Jul 20.

  PMID: 30036739 DERIVED

• Quidde J, Hegewisch-Becker S, Graeven U, Lerchenmuller CA, Killing B, Depenbusch R, Steffens CC, Lange T, Dietrich G, Stoehlmacher J, Reinacher A, Tannapfel A, Trarbach T, Marschner N, Schmoll HJ, Hinke A, Al-Batran SE, Arnold D. Quality of life assessment in patients with metastatic colorectal cancer receiving maintenance therapy after first-line induction treatment: a preplanned analysis of the phase III AIO KRK 0207 trial. Ann Oncol. 2016 Dec;27(12):2203-2210. doi: 10.1093/annonc/mdw425. Epub 2016 Oct 17.

  PMID: 27753609 DERIVED

• Hegewisch-Becker S, Graeven U, Lerchenmuller CA, Killing B, Depenbusch R, Steffens CC, Al-Batran SE, Lange T, Dietrich G, Stoehlmacher J, Tannapfel A, Reinacher-Schick A, Quidde J, Trarbach T, Hinke A, Schmoll HJ, Arnold D. Maintenance strategies after first-line oxaliplatin plus fluoropyrimidine plus bevacizumab for patients with metastatic colorectal cancer (AIO 0207): a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1355-69. doi: 10.1016/S1470-2045(15)00042-X. Epub 2015 Sep 8.

  PMID: 26361971 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Folic Acid; Capecitabine; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; 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

Study Officials

• Susanna Hegewisch-Becker, Prof. Dr.

  Onkologische Schwerpunktpraxis Eppendorf 20249 Hamburg Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2009
• First Posted: September 9, 2009
• Study Start: August 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: August 1, 2015
• Last Updated: September 1, 2015

Record last verified: 2015-08

Locations

DE (1)