Preoperative Chemoradiotherapy Utilizing Intensity Modulated Radiation Therapy in Combination With Bevacizumab-FOLFOX

NCT01395667 | Completed Phase 1

• 1 other identifier: 201103126MB
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

In this phase I trial neoadjuvant CCRT combining IMRT with three escalated dose levels (45 Gy, 50 Gy, and 55 Gy in 25 fractions) and BV-fluorouracil/ leucovorin/oxaliplatin (FOLFOX) regimens is planned for 15 locally advanced rectal cancer patients. The primary goal is to define the maximally tolerated dose of radiotherapy and the treatment related acute toxicity, and to demonstrate that preoperative highly conformal IMRT and concurrent BV-chemotherapy will lead to acceptable acute gastrointestinal morbidity. The secondary goal is to demonstrate that this treatment modality will elicit a comparable or improved rate of T stage downstaging and complete response pathologically.

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Maximally tolerated dose

  To define the maximally tolerated dose of radiotherapy and the treatment related acute toxicity and to demonstrate that preoperative highly conformal radiotherapy and concurrent bevacizumab-chemotherapy will lead to acceptable acute gastrointestinal morbidity

  5 years

Secondary Outcomes (1)

• Improved rate

  5 years

Study Arms (1)

Bevacizumab + CCRT followed by surgery

EXPERIMENTAL

Bevacizumab 5 mg/kg every 2 weeks + radiotherapy 45\~55 Gy/25 fractions, followed by total mesorectal excision

Other: CCRT

Interventions

CCRT OTHER

Combined IMRT with three escalated dose levels (45 Gy, 50 Gy, and 55 Gy in 25 fractions) and Bevacizumab-fluorouracil/ leucovorin/oxaliplatin (FOLFOX) regimens

Also known as: IMRT, Bevacizumab, Fluorouracil, Leucovorin, Oxaliplatin

Bevacizumab + CCRT followed by surgery

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy proven adenocarcinoma of the rectum located up to 15 cm from the anal verge on flexible endoscopy
• Patient evaluated by surgeon and found to be a potential surgical candidate. Since the objectives are response to chemoradiation and acute toxicity, lesions which are initially unresectable are eligible-provided the surgeon feels that, if there is sufficient response, surgery could become feasible
• Clinical evidence of T3 or T4, N0-N2 and M0 disease. This can be by imaging studies (transrectal ultrasound or MRI) or by physical findings (tethering on palpation for T3 lesions or invasion of a neighboring organ for T4 lesions)
• Karnofsky Performance Status \>70
• Laboratory criteria: Absolute neutrophil count \> 1.5 K; Platelets \> 100 K; Total Bilirubin \< 2.0; aspartate aminotransferase (AST) and Alkaline Phosphatase \< 2 x upper limit of normal; Creatinine \< 1.5; Hemoglobin \> 8.0; international normalized ratio (INR): \< 1.5
• Hepatitis B (HBsAg+) or hepatitis C virus (anti-HCV Ab+) carrier status (anti-viral agents allowed if clinically needed)
• Informed consent signed

You may not qualify if:

• Pregnant women, patient's age \< 20 years or \> 70 years, or patients unable to give informed consent
• Patients with a past history of pelvic radiotherapy
• Patients with any other malignancy within the past 5 years except: skin cancer or in-situ cervical cancer
• Patients with known allergy/intolerance to 5-FU, Leucovorin, Oxaliplatin, Bevacizumab
• Patients with prior chemotherapy for colorectal cancer
• Patients with grade \> 2 peripheral neuropathy
• Patients with any condition which, in the opinion of the treating medical oncologist, renders the patient unfit for 5FU, Leucovorin, Oxaliplatin chemotherapy and bevacizumab
• Patients with evidence of bleeding diathesis or coagulopathy, INR\>1.5
• Patients who require the use of warfarin sodium \> 1 mg
• Patients with active GI ulcers, GI bleeding, or active inflammatory bowel disease
• Patients with clinically significant cardiac disease (e.g., uncontrolled hypertension \[blood pressure of \>160/90 mmHg on medication\], history of myocardial infarction or unstable angina within 12 months of registration), New York Heart Association (NYHA) Class II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) are not eligible
• Patients with a history of aneurysms, cerebrovascular accident (CVA) and arteriovenous malformations
• Patients with arterial thromboembolic events, including transient ischemic attack (TIA), or clinically significant peripheral artery disease within 6 months of registration
• Patients with serious, non-healing wound, ulcer, or current healing fracture
• Patients with a history of any type of fistula (vesicovaginal, gastrointestinal, etc) or gastrointestinal perforation

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Bevacizumab; Fluorouracil; Leucovorin; Oxaliplatin

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; 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

Study Officials

• Jason CH Cheng, M.D. Ph.D.

  National Taiwan University Hospital

  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: July 14, 2011
• First Posted: July 15, 2011
• Study Start: June 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: November 10, 2016

Record last verified: 2016-11

Locations

TW (1)