Bortezomib, Fluorouracil, Leucovorin, and Oxaliplatin in Treating Patients With Advanced or Metastatic Colorectal Cancer

NCT00098982 | Completed Phase 1

• 3 other identifiers: EORTC-16029MILLENNIUM-EORTC-160292004-001763-21
• Study Type: interventional
• Target: 16
• Locations: 3 countries
• Sites: 3

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also help the chemotherapy drugs work better by making tumor cells more sensitive to the drugs. Giving bortezomib with fluorouracil, leucovorin, and oxaliplatin may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given with fluorouracil, leucovorin, and oxaliplatin in treating patients with advanced or metastatic colorectal cancer.

Conditions

Colorectal Cancer

Keywords

stage III colon cancer; stage IV colon cancer; stage III rectal cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose and recommended dose of bortezomib as measured by CTC v3.0

Secondary Outcomes (3)

• Safety as measured by CTC v3.0

• Response as measured by RECIST every 8 weeks

• Time to progression as measured by Kaplan Meier and RECIST every 8 weeks

Interventions

bortezomib DRUG

fluorouracil DRUG

leucovorin calcium DRUG

oxaliplatin DRUG

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed advanced or metastatic colorectal cancer * Amenable to first-line treatment with oxaliplatin, fluorouracil, and leucovorin calcium for advanced or metastatic disease * No symptomatic or radiologic evidence of brain metastases PATIENT CHARACTERISTICS: Age * Over 18 Performance status * ECOG 0-1 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 2,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN if liver metastases are present) * AST and ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present) Renal * Creatinine ≤ 1.7 mg/dL Cardiovascular * No ischemic heart disease within the past 6 months * No clinically significant ECG changes Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No baseline neuropathy \> grade 1 * No other prior or concurrent malignancy except cone-biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer * No unstable systemic disease * No active uncontrolled infection * No psychological, familial, sociological, or geographical condition that would preclude study participation * No hypersensitivity to bortezomib, boron, or mannitol PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior oxaliplatin * No prior chemotherapy for advanced or metastatic disease * At least 6 months since prior adjuvant chemotherapy Endocrine therapy * Not specified Radiotherapy * More than 4 weeks since prior radiotherapy Surgery * More than 14 days since prior major surgery

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (3)

Istituto Nazionale per lo Studio e la Cura dei Tumori

Naples, 80131, Italy

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Related Publications (2)

• Caponigro F, Lacombe D, Twelves C, Bauer J, Govaerts AS, Marreaud S, Milano A, Anthoney A. An EORTC phase I study of Bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer. Eur J Cancer. 2009 Jan;45(1):48-55. doi: 10.1016/j.ejca.2008.08.011. Epub 2008 Sep 20.

  PMID: 18809314 RESULT

• Lacombe DA, Caponigro F, Anthoney A, et al.: A phase I study of bortezomib in combination with 5FU/LV plus oxaliplatin in patients (pts) with advanced colorectal cancer (CRC): EORTC 16029. [Abstract] J Clin Oncol 25 (Suppl 18): A-4090, 2007.

  RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bortezomib; Fluorouracil; Leucovorin; Oxaliplatin

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes

Study Officials

• Francesco Caponigro, MD

  Istituto Nazionale per lo Studio e la Cura dei Tumori

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2004
• First Posted: December 9, 2004
• Study Start: September 1, 2004
• Primary Completion: January 1, 2007
• Last Updated: June 12, 2013

Record last verified: 2013-06

Locations

CH (1); GB (1); IT (1)