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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Taiwan University Hospital
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01395667
First received: July 14, 2011
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Rectal Cancer
Other: CCRT
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Trial of Preoperative Chemoradiotherapy Utilizing Intensity Modulated Radiation Therapy(IMRT)in Combination With Bevacizumab-FOLFOX for Patients With Locally Advanced Rectal Cancer

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Maximally tolerated dose [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Improved rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To demonstrate that preoperative highly conformal radiotherapy and concurrent bevacizumab-5-fluorouracil/leucovorin/oxaliplatin chemotherapy will elicit a comparable or improved rate of T stage downstaging and complete response pathologically (pCR).


Estimated Enrollment: 15
Study Start Date: June 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab + CCRT followed by surgery
Bevacizumab 5 mg/kg every 2 weeks + radiotherapy 45~55 Gy/25 fractions, followed by total mesorectal excision
Other: CCRT
Combined IMRT with three escalated dose levels (45 Gy, 50 Gy, and 55 Gy in 25 fractions) and Bevacizumab-fluorouracil/ leucovorin/oxaliplatin (FOLFOX) regimens
Other Names:
  • IMRT
  • Bevacizumab
  • Fluorouracil
  • Leucovorin
  • Oxaliplatin

Detailed Description:

Rectal cancer has been one of the leading cancers in Taiwan and other countries in the world. Preoperative neoadjuvant concurrent chemoradiotherapy (CCRT) is the well accepted and widely used modality for locally advanced rectal cancer, to improve the local control, reduce the treatment related toxicity, and to increase the anal preservation rate. Intensity modulated radiation therapy (IMRT), the most common advanced technique in recent 10 years, has been proven effective in dose escalation, treatment target conformity, and normal tissue sparing. The ongoing trials on rectal cancer increasingly adopt IMRT as the treatment technique. Bevacizumab (BV), the developed drug targeting on vascular endothelial growth factor, has been proven for its effective use in metastatic colorectal cancer. Besides, BV has showed its good radiosensitizing effects in the evolving neoadjuvant CCRT trials using traditional big-field pelvis radiotherapy on rectal cancer, the ongoing brain tumor trials, and the basic researches. Neoadjuvant CCRT using the combination of IMRT and BV may have the dual advantages of reduced treatment toxicity by technique and increased pathological response by radiosensitization for the possible improved outcomes. In this phase I trial neoadjuvant CCRT with combined 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 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.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Patients with intra-abdominal abscess within 6 months of study entry
  • Patients who have had an organ transplant
  • Patients with the placement of endorectal stent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01395667

Contacts
Contact: Jason CH Cheng, M.D. Ph.D jasoncheng@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Jason CH Cheng, M.D. Ph.D. National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01395667     History of Changes
Other Study ID Numbers: 201103126MB
Study First Received: July 14, 2011
Last Updated: April 15, 2014
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Bevacizumab
Fluorouracil
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 16, 2014