Neoadjuvant Chemoradiation With RHUMAB VEGF (Avastin) for Rectal Cancer

NCT00113230 | Completed Phase 2 Results

• 1 other identifier: 2003-0832
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Preoperative chemoradiation leads to increased pelvic control and overall survival, but both distant and local disease control remain problematic in locally advanced rectal cancer patients. Enhancing the effect of chemotherapy and radiotherapy can increase tumor response as well as distant disease control. Patients who have complete response to therapy have increased sphincter preservation, and can possibly have more limited surgery (full thickness local excision). When combined with standard chemotherapy, bevacizumab \[RHUMAB VEGF, Avastin\] has been shown to improve response and median survival in patients with metastatic colorectal cancer in a recent randomized trial, has led to increased activity in preclinical studies with radiotherapy, and has been found to be very well tolerated with chemoradiation in a phase I trial conducted at the M.D. Anderson Cancer Center (MDACC) in patients with locally advanced pancreatic cancer. The hypothesis is that the addition of bevacizumab to standard chemoradiation will safely lead to increased tumor response in patients with locally advanced rectal cancer.

Conditions

Rectal Cancer

Keywords

Rectal Cancer; Bevacizumab; RHUMAB VEGF; Avastin; Capecitabine; Neoadjuvant Concurrent Capecitabine; Xeloda; Radiation; Radiotherapy; Radiation Therapy; XRT

Outcome Measures

Primary Outcomes (1)

• Pathologic Local Tumor Response

  At follow-up evaluation after completion of neoadjuvant and surgical therapy, resected primary tumor classified based on routine pathology staining in the following manner: Pathologic Complete Response (no evidence of residual cancer); Microscopic Residual (no grossly detected disease, but evidence of microscopic residual disease); and Gross Residual Disease.

  Baseline to approximately 5 Months (Following 28 days of treatment, chemotherapy and surgical resection of tumor)

Study Arms (1)

Avastin

EXPERIMENTAL

Capecitabine, Avastin (RHUMAB VEGF/Bevacizumab) And Radiotherapy

Drug: Avastin (Bevacizumab, RHUMAB VEGF); Drug: Capecitabine; Radiation: Radiation Therapy

Interventions

Avastin (Bevacizumab, RHUMAB VEGF) DRUG

Starting Dose 5 mg/kg intravenously on day one of radiotherapy, given every 2 weeks +/- 2 days for a total of 3 doses.

Also known as: RHUMAB VEGF, Avastin, Bevacizumab

Avastin

Capecitabine DRUG

900 mg/m\^2 by mouth twice a day during days of radiation for all five weeks of therapy.

Also known as: Xeloda

Avastin

Radiation Therapy RADIATION

45 Gy in 25 fractions to the pelvis followed by 5.4 Gy as a boost dose to the primary tumor with margin, for a total dose of 50.4 Gy over 28 treatment days.

Also known as: XRT, Radiotherapy

Avastin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ECOG status of 0 or 1.
• Patients must be greater than or equal to 18 years of age.
• All patients must have histologically confirmed adenocarcinoma of the rectum with pathologic material reviewed by the Department of Pathology at MDACC. The clinical stage must be T3, T4, or recurrent based on CT, MRI or EUS criteria.
• All patients must have no distant metastatic disease on abdominopelvic CT scan performed with IV contrast. If the CT was performed outside of MDACC, the slice thickness is 7.5 mm. Criteria for pathologic enlargement of lymph nodes is \> 15 mm on short axis dimension. If CT findings of lung, liver, or peritoneal metastases are equivocal, patients are eligible to participate.
• The rectal tumor must be either palpable on digital rectal exam or the inferior edge of the tumor must be within 12 cm of the anal verge based on rigid proctoscopy.
• Patients must have WBC \> 4000 cells/mm3, ANC of \>1500/L, platelets \> 100,000/mm3, total serum bilirubin \< 2.0 mg%, BUN \< 30 mg%, creatinine \< 1.5 mg% and/or creatinine clearance \>30ml/min (estimated as calculated with Cockcroft-Gault equation). Note: In patients with moderate renal impairment (estimated creatinine clearance 30-50 mL/min) at baseline, a dose reduction to 75% of the capecitabine starting dose is recommended.
• Hemoglobin of \>9 gm/dL (may be transfused or receive Procrit to maintain or exceed this level)
• Patients must have signed informed consent indicating that they are aware of the investigational nature of the study, and are aware that participation is voluntary.

You may not qualify if:

• Known compromised renal or hepatic function.
• Participation in any other experimental drug study.
• AST or ALT \>5 times upper limit of normal for subjects with documented liver metastases; \>2.5 times the upper limit of normal for subjects without evidence of liver metastases.
• Pregnant or lactating woman. Woman of childbearing potential with either a positive or no pregnancy test at baseline. Woman / men of childbearing potential not using a reliable contraceptive method. (Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential). Patients must agree to continue contraception for 30 days from the date of the last study drug administration.
• Any prior chemotherapy.
• Any prior radiation therapy.
• Serious, uncontrolled, concurrent infection(s) requiring IV antibiotics.
• Treatment for other carcinomas within the last five years, except cure non-melanoma skin cancer and treated in-situ cervical cancer.
• Clinically significant cardiac disease (e.g., uncontrolled hypertension \[blood pressure of \>160/110 mmHg on medication\], any history of myocardial infarction, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix H), unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or grade II or greater peripheral vascular disease(see Appendix H).
• Inability to to swallow oral medication.
• Evidence of bleeding diathesis or coagulopathy, INR greater than or equal to 1.5.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; fine needle aspirations or core biopsies within 7 days prior to Day 0.
• Proteinuria at baseline or clinically significant impairment of renal function Subjects unexpectedly discovered to have 1+ proteinuria at baseline should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate \<500 mg of protein/24 hr to allow participation in the study (see appendix F).
• Currently has serious, nonhealing wound, ulcer, or bone fracture.
• Had aneurysms, strokes, transient ischemic attacks, and arteriovenous malformations within the past year.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

UT M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• The University of Texas M.D.Anderson Cancer Center

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Bevacizumab; Capecitabine; Radiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal 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; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Results Point of Contact

• Title: Christopher H. Crane, MD / Associate Professor
• Organization: UT MD Anderson Cancer Center

713-792-2933

Study Officials

• Christopher H. Crane, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2005
• First Posted: June 7, 2005
• Study Start: February 1, 2005
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: August 7, 2012
• Results First Posted: November 13, 2009

Record last verified: 2012-07

Locations

US (1)