DCE-MRI PET Bevacizumab Study in Rectal Cancer

This study is currently recruiting participants.
Verified February 2013 by Abramson Cancer Center of the University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01426074
First received: August 29, 2011
Last updated: February 25, 2013
Last verified: February 2013
  Purpose

This study will determine the following: the response rate (including pathological CR rate), TTP, and complications of treatment in patients with rectal cancer treated with FOLFOX bevacizumab, the alteration of tumor blood flow (assessed by DCE-MRI as percentage change in Ktrans) after 1 cycle of bevacizumab therapy compared to baseline value in patients treated with FOLFOX alone and those treated with bevacizumab at 5 mg/kg., the degree of hypoxis (measured by tumor uptake of the 2-nitroimidazole EF5) induced by bevacizumab treatment and its relationship to changes in tumor blood flow, and the degree of apoptosis (measured by tumor uptake of di-annexin V) induced by bevacizumab treatment and its relationship to changes in tumor blood flow.


Condition Intervention Phase
Rectal Cancer Patients
Drug: Bevacizumab 5 mg/kg
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase II/Pharmacodynamic Study of Preoperative or Definitive FOLFOX Plus Bevacizumab, With the Additional Pharmacodynamic Goal of Assessing Tumor Blood Flow as Measured by Dynamic Contrast-enhanced MRI, and the Induction of Hypoxia and Apoptosis as Measured by PET in Patients With Rectal Cancer

Resource links provided by NLM:


Further study details as provided by Abramson Cancer Center of the University of Pennsylvania:

Primary Outcome Measures:
  • Pathologic Complete Response (pCR) [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: August 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Bevacizumab 5 mg/kg
    Intravenously every two weeks
Detailed Description:

The primary objectives of this study will determine the following: the response rate (including pathological CR rate), TTP, and complications of treatment in patients with rectal cancer treated with FOLFOX bevacizumab, the alteration of tumor blood flow (assessed by DCE-MRI as percentage change in Ktrans) after 1 cycle of bevacizumab therapy compared to baseline value in patients treated with FOLFOX alone and those treated with bevacizumab at 5 mg/kg., the degree of hypoxis (measured by tumor uptake of the 2-nitroimidazole EF5) induced by bevacizumab treatment and its relationship to changes in tumor blood flow, and the degree of apoptosis (measured by tumor uptake of di-annexin V) induced by bevacizumab treatment and its relationship to changes in tumor blood flow. The secondary objectives of this study is to determine in an exploratory fashion the relationship between tumor blood flow, hypoxia induction, and apoptosis induction , and time to progression in patients continuing on to receive Bevacizumab 5 mg/kg, to analyze archival tumor from the patients treated in this trial for mutations in the MKK7 and SEK1 genes, and by semi-quantitative IHC for these and other relevant proteins, to determine the relationship between vascular proliferation as measured by DCE-MRI and markers of endothelial cell proliferation, and to obtain pilot data on whether assays that measure vascular endothelial cell mitogenic stimulation and mitogenic activity may predict response to therapy, time to progression and overall survival in patients receiving bevacizumab 5 mg/kg.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically documented advanced or metastatic adenocarcinoma of the rectum, T3 or T4, N any, M0 or M1. Patients must have available and identified tissue for immunohistochemical analysis and agree to submit it for the correlative endpoints. When available, formalin-fixed,paraffin-embedded tissue from previous biopsy or surgical resection will suffice.
  • Patients must measurable disease as defined by the RECIST criteria as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20mm with conventional techniques on either CT, MRI, or EUS. marker (CEA) elevation alone is in sufficient for entry.
  • Patients may have had prior adjuvant treatment of rectal cancer. The prior treatment regimen must not have included bevacizumab but may have included oxaliplatin and the last dose of chemotherapy must have been > 6 months prior to study entry. Patients with prior radiotherapy are acceptable. It must be at least 2 weeks since administration of radiation therapy and all signs of toxicity must have abated.
  • Patients with prior malignancies other than colorectal cancer are allowed, provided they have been treated with curative, intent, and have no evidence of recurrence of that malignancy.
  • Patients must be age 18 years or older.
  • Patients must have an ECOG performance status of 0-1.
  • The following required required Initial Laboratory Values should be obtained within 4 weeks of the start of treatment:

Granulocytes ≥ 1,500/ml Platelet Count ≥ 100,000/ml Creatinine ≤ 1.5 x upper limit of normal Bilirubin ≤ 1.5 x upper limit of normal AST ≤ 5 x upper limit of normal Urine: Urine protein: creatinine ration ≤ 1.0 at screening

  • Patients must not be pregnant or lactating as chemotherapy is though to present substantial risk to the fetus/infant
  • Patients must have a life expectancy of greater than three months.
  • Patients must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients may not be receiving any other investigational agents.
  • Patients with the following contraindication to MRI are excluded: Hypersensitivity to gadolinium Contraindicated metallic device, including pacemaker, non-MRI compatible aneurysm clip, other non-MRI compatible mechanical and/or electrical device, or metallic fragments.
  • Patients with severe claustrophobia
  • Patients with a history of allergic reactions attributed to Flagyl (metronidazole) which has a chemical structure similar to EF5 are excluded.
  • Patients with T1 or T2 N0M0 disease are not eligible.
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days to Day 0, anticipation of need for major surgical procedure during the course of the study. Minor surgical procedures such as port placement, fine needle aspirations or core biopsies within 3 days prior to Day 0.
  • Patients with serious nonhealing wounds, ulcers, or bone fractures.
  • Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0.
  • Patients with a history of myocardial infarction, unstable angina, or cerebrovascular accident < 6 months prior to registration.
  • Patients with clinically significant peripheral vascular disease.
  • Patients with New York Heart Association Class II or greater congestive heart failure (Class II is defined as symptoms of fatigue, dyspnea or other symptoms with ordinary physical activity) See Appendix E.
  • Patients using oral or parenteral anticoagulation are not excluded provided they are on a stable dose of anticoagulant.
  • patients with pre-existing hypertension should be on a stable antihypertensive regimen and have a blood pressure ≤ 150/100 mmHg at the time of enrollment.
  • Patients must not have known brain metastases because the study drug has not been adequately tested in this setting.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01426074

Contacts
Contact: Peter O'Dwyer, MD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Peter O'Dwyer, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Investigators
Principal Investigator: Peter O'Dwyer, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01426074     History of Changes
Other Study ID Numbers: UPCC 05209
Study First Received: August 29, 2011
Last Updated: February 25, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014