Bortezomib, Fluorouracil, and External-Beam Radiation Therapy in Treating Patients With Stage II, Stage III, or Stage IV Rectal Cancer

NCT00280176 | Completed Phase 1 DMC

• 2 other identifiers: LCCC 0209CDR0000549844
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bortezomib and fluorouracil together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with fluorouracil and external-beam radiation therapy in treating patients with stage II, stage III, or stage IV rectal cancer.

Conditions

Colorectal Cancer

Keywords

recurrent rectal cancer; stage II rectal cancer; stage III rectal cancer; stage IV rectal cancer; adenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose

  6 weeks

• Dose-limiting toxicity

  8 weeks

Secondary Outcomes (5)

• Dose-effect relationship of bortezomib on NF-kappa B activation induced by chemoradiotherapy

  6 weeks

• Downstream events induced by NF-kappa B activation

  8 weeks

• Downstream events related to activation of p53 in response to treatment with chemoradiotherapy and bortezomib

  8 weeks

• Rate of complete pathologic remission

  2 years

• Gene expression pattern of tumors as assessed by cDNA microarray analysis pre- and post-treatment

  8 weeks

Interventions

bortezomib DRUG

0.7mg/m2 - 1.5mg.m2 given during Weeks 1, 2, 4 and 5 on a Monday/Thursday or Tuesday/Friday schedule, up to six weeks

Also known as: Velcade

fluorouracil DRUG

225mg/m2 given weekly, up to 6 weeks

Also known as: 5FU

radiation therapy RADIATION

180 cGy, every 5 days, up to six weeks

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Biopsy confirmed diagnosis of adenocarcinoma of the rectum meeting 1 of the following clinical staging criteria: * T3-T4, N0, M0 (stage II disease) * T4 disease defined as tumor fixed on examination or involving adjacent pelvic structures, such as the sidewall, bladder, uterus, prostate, or small bowel by ultrasound or CT scan * Any T, N1-2, M0 (stage III disease) * Any T, any N, M1 (stage IV disease) * Recurrent disease (any prior stage) * Candidate for local palliative therapy or curative resection of metastatic disease * Previously treated CNS disease allowed provided it is stable for \> 3 months PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy \> 3 months * Adequate nutrition * WBC ≥ 4,000/mm³ * ANC \> 2,000/mm³ * Platelet count ≥ 100,000/mm³ * Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min * Bilirubin ≤ 1.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No serious medical or psychiatric illness that would limit study compliance or limit survival to \< 2 years * No history of refractory congestive heart failure or cardiomyopathy * No active coronary artery disease, myocardial infarction within the past 3 months, or cerebrovascular accident within the past 3 months * No peripheral neuropathy ≥ grade 2 * No hypersensitivity to bortezomib, boron, or mannitol PRIOR CONCURRENT THERAPY: * More than 1 week since prior major surgery * More than 28 days since prior investigational agents * Prior chemotherapy allowed * No prior pelvic radiotherapy (for treatment of any pelvic malignancy) * No concurrent herbal medication (excluding vitamin and mineral supplements) * No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

Bortezomib; Fluorouracil; Radiotherapy

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; Therapeutics

Study Officials

• Bert H. O'Neil, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2006
• First Posted: January 20, 2006
• Study Start: April 1, 2003
• Primary Completion: November 1, 2008
• Study Completion: September 1, 2010
• Last Updated: February 14, 2012

Record last verified: 2012-02

Locations

US (2)