Combination Chemotherapy and Bevacizumab With or Without Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer

NCT00462501 | Completed Results

• 3 other identifiers: 07-021P30CA008748MSKCC-07021
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of rectal cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy and bevacizumab together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This clinical trial is studying how well giving combination chemotherapy and bevacizumab with or without radiation therapy works in treating patients with locally advanced rectal cancer

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Complete Pathologic Response

  This will be assessed on the basis of the surgical pathology report.

  3 years

Study Arms (1)

Chemotherapy and Bevacizumab With or Without Radiation

EXPERIMENTAL

FOLFOX/Bevacizumab will be given for 4 cycles over 8 weeks; FOLFOLX6 without Bevacizumab will be given for an additional 2 cycles over 4 weeks. Oxaliplatin will be given on Day 1 of each cycle over 2 hours at 85 mg/m2 IV. Leucovorin will be given Day 1 of each cycle over 2 hours at 400 mg/m2 IV. Fluorouracil will be given on Day 1 of each cycle at 400 mg/m2 IVP, then Fluorouracil will be given at 1200 mg/m2 IVCI over Day 1 and 2. Bevacizumab will be given at 5mg/kg over 10 minutes on day 1. Patients will undergo re-staging within 3 weeks of completing their 6th cycle of FOLFOX. If the reassessment reveals that there has been no disease progression as compared to the pre-treatment evaluation and the patient remains a candidate for an R0 resection. If the surgical oncologist's reassessment is that the patient is not a candidate for an R0 resection, the patient will proceed to standard pre-operative radiation with synchronous infusional 5-fluorouracil.

Biological: bevacizumab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Procedure: conventional surgery; Radiation: radiation therapy

Interventions

bevacizumab BIOLOGICAL

Chemotherapy and Bevacizumab With or Without Radiation

fluorouracil DRUG

Chemotherapy and Bevacizumab With or Without Radiation

leucovorin calcium DRUG

Chemotherapy and Bevacizumab With or Without Radiation

oxaliplatin DRUG

Chemotherapy and Bevacizumab With or Without Radiation

conventional surgery PROCEDURE

Chemotherapy and Bevacizumab With or Without Radiation

radiation therapy RADIATION

Chemotherapy and Bevacizumab With or Without Radiation

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically or pathologically confirmed adenocarcinoma of the rectum * Clinical stage T1, N1; T2, N1; T3, N0; or T3, N1 by endorectal ultrasonography (ERUS) * No bulky N2 disease by either ERUS or MRI * No primary fixed or unresectable (clinical stage T4) rectal cancer or recurrent colorectal cancer limited to the pelvis * Primary unresectable rectal cancer is defined as a primary rectal tumor which on the basis of either physical exam, ERUS or pelvic MRI is deemed to be adherent or fixed to adjacent pelvic structures * Must be a candidate for all of the following: * Neoadjuvant chemoradiotherapy * Systemic therapy with fluorouracil, leucovorin calcium, oxaliplatin (FOLFOX), and bevacizumab * Complete surgical resection via low anterior resection prior to administration of any therapy * No low-lying tumors deemed to require an abdominal perineal resection * No large or bulky tumors that require a diverting colostomy or placement of an endorectal stent prior to treatment initiation * No clinical evidence of metastatic disease PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count \> 150,000/mm\^3 * Hemoglobin \> 8.0 g/dL * Creatinine ≤ 1.5 times upper limit of normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 4 weeks after completion of study therapy * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No arterial thrombotic event within the past 6 months, including stable or unstable angina, myocardial infarction (MI), or cerebral vascular accident (CVA) * Deep venous thrombosis, pulmonary embolus, MI, CVA, atrial fibrillation, or any other conditions occurring more than 6 months ago allowed provided patient is on stable doses of anticoagulant therapy * No other medical or psychiatric condition or disease that would preclude study therapy PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior chemotherapy or surgery for rectal cancer * No prior pelvic radiotherapy * No other concurrent experimental therapy, including any of the following: * Chemotherapy * Radiotherapy * Hormonal therapy * Antibody therapy * Immunotherapy * Gene therapy * Vaccine therapy * Angiogenesis inhibitors * Matrix metalloprotease inhibitors * Thalidomide * Anti-vascular endothelial growth factor/Flk-1 monoclonal antibody * Any other experimental drugs

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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Fluorouracil; Leucovorin; Oxaliplatin; 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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Therapeutics

Results Point of Contact

• Title: Dr. Leonard Saltz
• Organization: Memorial Sloan Kettering Cancer Center

saltzl@mskcc.org

646-888-4286

Study Officials

• Leonard B. Saltz, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Karyn A. Goodman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Martin Weiser, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2007
• First Posted: April 19, 2007
• Study Start: March 1, 2007
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: January 20, 2016
• Results First Posted: January 20, 2016

Record last verified: 2015-12

Locations

US (1)