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

NCT01894451 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 13-147
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Inflammatory Breast Carcinoma

Keywords

Inflammatory Breast Carcinoma; 89Zr-bevacizumab

Outcome Measures

Primary Outcomes (1)

• Quality Control Standards for Radiopharmamceuticals and Number of Successfully Acquired 89Zr-bevacizumab-PET/CT scans

  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.

  2 years

Secondary Outcomes (5)

• Number of related adverse events after the intravenous administration of 89Zr-bevacizumab.

  2 years

• Biodistribution of 89Zr-bevacizumab and individual organ and effective dose of 89Zr-bevacizumab

  2 Years

• Amount of 89Zr-bevacizumab uptake in IBC tumor and measures of tumor angiogenesis in research biopsy specimens.

  2 Years

• Changes in tumor uptake of 89Zr-bevacizumab and FDG during and after preoperative chemotherapy and response in primary IBC tumor MRI.

  2 Years

• To correlate the changes in tumor uptake on 89Zr-bevacizumab-PET/CT with standard imaging response using MRI and FDG-PET/CT

  2 Years

Other Outcomes (2)

• Visualization of primary IBC tumor and visualization and number of distant metastases

  2 years

• 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

  2 years

Study Arms (1)

89Zr-bevacizumab-PET/CT Scan

EXPERIMENTAL

* 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; Procedure: FDG-PET/CT; Procedure: MRI scan; Procedure: Tumor biopsies

Interventions

89Zr-bevacizumab DRUG

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.

89Zr-bevacizumab-PET/CT Scan

FDG-PET/CT PROCEDURE

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.

89Zr-bevacizumab-PET/CT Scan

MRI scan PROCEDURE

• 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.

89Zr-bevacizumab-PET/CT Scan

Tumor biopsies PROCEDURE

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.

89Zr-bevacizumab-PET/CT Scan

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Participants must have histologically or cytologically confirmed HER2 negative 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Brigham and Womens Hospital

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Inflammatory Breast Neoplasms

Interventions

89Zr-bevacizumab; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Heather A Jacene, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 25, 2013
• First Posted: July 10, 2013
• Study Start: June 1, 2015
• Primary Completion: March 17, 2017
• Study Completion: March 17, 2017
• Last Updated: December 12, 2019

Record last verified: 2019-12

Locations

US (2)