Pilot Study of Zirconium-89 Bevacizumab Positron Emission Tomography for Imaging Angiogenesis in Patients With Inflammatory Breast Carcinoma Receiving Preoperative Chemotherapy

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by Dana-Farber Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Heather A. Jacene, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01894451
First received: June 25, 2013
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

This research study is a pilot study, which tests the ability of an investigational compound to be used in humans for further studies. "Investigational" means that 89Zr-bevacizumab for PET/CT imaging is being studied. It also means that the FDA (U.S. Food and Drug Administration) has not approved 89Zr-bevacizumab for PET/CT imaging for use in patients, including people with your type of cancer.

89Zr-bevacizumab is a newly developed radiotracer. Radiotracers are compounds or drugs that are attached to small amounts of a radioactive substance. The amount of the compound or drug in a radiotracer is also very small. Radiotracers are used to make images of processes that are happening in the body, but they do not affect how the body works. 89Zr-bevacizumab is made up of the drug bevacizumab and the radioactive substance zirconium-89 (89Zr). 89Zr-bevacizumab is used for an imaging procedure called positron emission tomography/computed tomography (PET/CT). This radiotracer has been used in other research studies. Information from those other research studies suggests that 89Zr-bevacizumab-PET/CT imaging may be able to measure new blood vessel formation to determine where the cancer is in your body and if your cancer is being killed by chemotherapy.


Condition Intervention Phase
Inflammatory Breast Carcinoma
Drug: 89Zr-bevacizumab
Procedure: FDG-PET/CT
Procedure: MRI scan
Procedure: Tumor biopsies
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Pilot Study of Zirconium-89 Bevacizumab Positron Emission Tomography for Imaging Angiogenesis in Patients With Inflammatory Breast Carcinoma Receiving Preoperative Chemotherapy

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Quality Control Standards for Radiopharmamceuticals and Number of Successfully Acquired 89Zr-bevacizumab-PET/CT scans [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    In order to determine if 89Zr-bevacizumab-PET/CT scanning is feasible, we will determine results of radiolabeling of chelated bevacizumab including the radiolabeling yield, specific activity, and radiochemical purity and the number of successfully acquired 89Zr-bevacizumab-PET/CT scans.


Secondary Outcome Measures:
  • Number of related adverse events after the intravenous administration of 89Zr-bevacizumab. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the safety of 89Zr-bevacizumab-PET/CT imaging in patients with IBC, the number of adverse events related to the radiotracer (89Zr-bevacizumab) will be determined.

  • Biodistribution of 89Zr-bevacizumab and individual organ and effective dose of 89Zr-bevacizumab [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
  • Amount of 89Zr-bevacizumab uptake in IBC tumor and measures of tumor angiogenesis in research biopsy specimens. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    The amount of 89Zr-bevacizumab uptake in IBC tumor will be primarily given by standardized uptake values from PET/CT imaging. Measures of tumor angiogenesis are intratumoral microvessel density (MVD), vessel diameter, and vascular pericyte coverage

  • Changes in tumor uptake of 89Zr-bevacizumab and FDG during and after preoperative chemotherapy and response in primary IBC tumor MRI. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    This outcome aims to determine if 89Zr-bevacizumab provides similar results in regards to monitoring therapy response compared to standard modalities, FDG-PET/CT and MRI breast

  • To correlate the changes in tumor uptake on 89Zr-bevacizumab-PET/CT with standard imaging response using MRI and FDG-PET/CT [ Time Frame: 2 Years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Visualization of primary IBC tumor and visualization and number of distant metastases [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    This is an exploratory outcome measure to see if 89Zr-bevacizumab detects primary and metastatic IBC tumor in a similar fashion

  • Percent change in 89Zr-bevacizumab tumor uptake in primary IBC tumor between the baseline and post preoperative chemotherapy PET/CT scans and residual cancer burden at mastectomy/tissue sampling if residual disease [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    This outcome measure is exploratory to investigate whether changes in tumor uptake of 89Zr-bevacizumab can predict response in mastectomy specimens.


Estimated Enrollment: 10
Study Start Date: October 2014
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 89Zr-bevacizumab-PET/CT Scan
  • 89Zr-bevacizumab-PET/CT will be performed at baseline, after 2 cycles of preoperative chemotherapy, and at the completion of preoperative chemotherapy.
  • The 89Zr-bevacizumab-PET/CT imaging procedure is detailed in Appendix A and is briefly described below.

Participants will be injected with 1 mCi of 89Zr-bevacizumab intravenously and PET/CT images will be obtained at 3-4 days after 89Zr-bevacizumab administration to allow time for antibody accumulation in the tumor. Imaging will be performed on a Centers for Quantitative Imaging Excellence (CQIE) qualified PET/CT scanner at the Dana-Farber Cancer Institute. After the baseline scan, subsequent scans will be obtained on the same PET/CT scanner for an individual participant.

Drug: 89Zr-bevacizumab
89Zr-bevacizumab is a newly developed radiotracer. Radiotracers are compounds or drugs that are attached to small amounts of a radioactive substance. The amount of the compound or drug in a radiotracer is also very small. Radiotracers are used to make images of processes that are happening in the body, but they do not affect how the body works. 89Zr-bevacizumab is made up of the drug bevacizumab and the radioactive substance zirconium-89 (89Zr). 89Zr-bevacizumab is used for an imaging procedure called positron emission tomography/computed tomography (PET/CT). 89Zr-bevacizumab-PET/CT will be performed in this study at baseline, after 2 cycles of preoperative chemotherapy and at the completion of chemotherapy.
Procedure: FDG-PET/CT
FDG-PET/CT scan: Pictures of your organs will be taken using a PET (Positron Emission Tomography) scanner. At the same time, a CT (computed tomography) scan will be performed. FDG, a radioactive substance similar to glucose (or sugar), will be injected into your vein using a needle prior to performing the PET/CT scan. After the injection, you will be asked to sit quietly for one hour to let the FDG absorb into the body. After this hour, you will be asked to lie flat on your back for up to 50 minutes while the PET and CT images are being taken. This FDG-PET/CT scan is part of regular cancer care. If you have had this test within 14 days of study enrollment, you may or may not have to have this test repeated.
Procedure: MRI scan
• MRI Scan: MRI (Magnetic Resonance Imaging) scans of the breast will be taken. You will receive an injection of a dye before the MRI. You will be asked to lie flat on your back in the scanner for up to 30 minutes for pictures to be taken. This MRI scan is part of regular cancer care. If you have had this test within 14 days of study enrollment , you may or may not have to have this test repeated.
Procedure: Tumor biopsies
Tumor biopsies: Prior to starting your treatment, a radiologist will use breast MRI or ultrasound imaging to localize an area of your tumor in the breast for a research biopsy. The biopsy procedure is done in an outpatient setting using a done using a needle to obtain tissue. A local anesthetic will be given to minimize any pain; however, after the procedure you can expect some discomfort and possible bruising. This biopsy is part of research.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants must meet the following criteria on screening examination to be eligible to participate in the study:

  • Participants must have histologically or cytologically confirmed invasive breast adenocarcinoma.
  • Participants must have clinical characteristics consistent with IBC, characterized by a rapid onset of clinical findings exemplified as diffuse edema and erythema of the breast, often without a palpable mass.
  • Age ≥ 21 years. Because no dosing or adverse event data are currently available on the use of 89Zr-bevacizumab in participants <21 years of age, children are excluded from this study but will be eligible for future pediatric trials.
  • Any stage is eligible.
  • Participants must be eligible for preoperative chemotherapy for IBC as determined by the treating physician.
  • The effects of 89Zr-bevacizumab on the developing human fetus are unknown. For this reason and because radiopharmaceuticals may be teratogenic, women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability and willingness to comply with the study procedures.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Participants must be willing to have research biopsies at baseline and after 2 cycles of preoperative chemotherapy, and possibly at the completion of preoperative chemotherapy.
  • ECOG performance status ≤ 2.

Exclusion Criteria:

  • Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
  • Pregnant women are excluded from this study because 89Zr-bevacizumab and 18F-FDG are radiopharmaceuticals with the potential for teratogenic effects. Because of the radiation exposure to a nursing infant from 89Zr-bevacizumab and 18F-FDG, women who are breastfeeding are also excluded from this study. In addition, bevacizumab may cause fetal harm based on animal studies (2).
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Major surgery or significant bleeding episodes within 28 days before study initiation. Major surgery does not include: breast or other biopsies obtained for diagnosis, placement of radio-opaque clip to localize a tumor or tumors for subsequent surgical resection, placement of central venous access, pretreatment lymph node sampling. Significant bleeding episodes are defined for the purpose of this study as hemoptysis or upper/lower gastrointestinal bleeding.

Although bevacizumab will be administered in tracer quantities in this study and is not expected to have pharmacologic effects, participants with major surgery or significant bleeding episodes within 28 days before study initiation may be at a higher risk of bleeding.

Contraindications for MRI with contrast or PET/CT including:

  • Cardiac pacemaker, implanted cardiac defibrillator, pacing wires, internal electrodes
  • Aneurysm clips
  • Cochlear, otologic, or other ear implant
  • Tissue expander
  • Swan-Ganz or Thermo Dilution
  • Moderate renal insufficiency (estimated GFR less than 60 mL/min/1.73 m2) to end stage renal disease (estimated GFR less than 15 mL/min/1.73 m2 or a serum creatinine more than 3 mg/dL), who are not on dialysis, and patients with renal failure on chronic dialysis
  • Severe claustrophobia
  • History of multiple or severe allergic reactions attributed to immunoglobulins or MRI contrast agents.
  • Any past or current condition that in the opinion of the study investigators would confound the results of the study or pose additional risk to the patient by their participation in the study.
  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: NCT01894451

Contacts
Contact: Heather A Jacene, MD 617-632-3767 hjacene@partners.org

Locations
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Heather A Jacene, MD    617-632-3767    hjacene@partners.org   
Principal Investigator: Heather A Jacene, MD         
Brigham and Womens Hospital Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Heather A Jacene, MD    617-632-3767    hjacene@partners.org   
Principal Investigator: Heather A Jacene, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Heather A Jacene, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Heather A. Jacene, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01894451     History of Changes
Other Study ID Numbers: 13-147
Study First Received: June 25, 2013
Last Updated: February 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Inflammatory Breast Carcinoma
89Zr-bevacizumab

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Inflammatory Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
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 July 24, 2014