FDHT PET and Bicalutamide in Metastatic Breast Cancer

November 26, 2019 updated by: C.P. Schroder, University Medical Center Groningen

FDHT-PET to Visualize the Effect on the Androgen Receptor Level by Bicalutamide

Rationale: The purpose is to evaluate whether non-invasive in vivo imaging of androgen receptor (AR) presence in metastatic breast cancer patients by means of 18F-fluoro-dihydrotestosterone positron emission tomography (FDHT-PET) can be used to predict (early) treatment response to, and optimal dosing of, the anti androgen bicalutamide. The ultimate goal is to contribute to optimal selection of breast cancer patients for anti androgen treatment. Objective: Feasibility to detect a diffrence in uptake on 18F-FDHT scan after 6 weeks of treatment with bicalutamide in metastatic breast cancer patients. Secondary Objectives: to describe whether changes in 18F-FDHT tracer uptake after six weeks associates with response to bicalutamide, to describe whether changes in AR availability are different for breast cancer subgroups during treatment with bicalutamide and to describe whether 18F-FDHT tracer uptake is influenced by the amount of AR tumor expression. Study design: This is a single arm, one stage feasibility study, which will be executed in the University Medical Center Groningen, The Netherlands. The primary endpoint of the study is to evaluate the difference in 18F-FDHT uptake in tumor lesions after 6 weeks of bicalutamide treatment in patients with AR-positive metastatic breast cancer. Patients will be treated with bicalutamide until progression or unacceptable toxicity is encountered. Study population: The investigators will include 20 postmenopausal metastatic breast cancer patients with an AR positive, HER2 negative tumor. Patients should be restaged clinically with bone scintigraphy and CT scan within a 6 week timeframe of the PET examinations. Intervention: All patients will receive a baseline FDHT-PET scan and start with bicalutamide treatment 150mg daily. During follow-up patients will receive one FDHT-PET scan after 6 weeks. Treatment with bicalutamide will continue until progression or unacceptable toxicity is encountered. Main study endpoint: The percent difference in 18F-FDHT uptake in tumor lesions after 6 weeks of monotherapy bicalutamide. A minimum decrease of 20% in 18F-FDHT uptake after 6 weeks compared to baseline uptake with an α of 0.05 and a power of 80%, is considered clinical significant.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. A history of histological proven AR-positive (i.e. >10% staining), HER2-negative metastatic breast cancer (preferably assessment on fresh metastasis biopsy, alternatively archival metastasis biopsy)
  2. Tumor progression after at least one line of systemic treatment
  3. Measurable disease according to RECIST 1.1; or evaluable disease
  4. Age ≥ 18 years

  5. Postmenopausal status defined as one of the following:

    • Age ≥60 years
    • Previous bilateral oophorectomy
    • Age <60 years and amenorrhea for >12 months in the absence of interfering hormonal therapies (such as LH-RH agonists and ER-antagonists
    • Age <60 years using ER antagonists should have amenorrhea for >12 months and FSH >24U/L and LH>14U/L

  6. Adequate hematological, renal and liver function as follows:

    • Absolute neutrophil count > 1.5 x 109/L
    • Platelet count >100 x 109/L
    • White blood cell count >3 x 109/L
    • AST and ALT <3.0 x upper limit of normal (ULN)
    • Alkaline phosphatase <2.5 x ULN
    • Creatinine clearance >50mL/min
    • Lipase/amylase <1/5 x ULN
    • Protrombin time, partial tromboplastin time and INR <1.5 x ULN
  7. Written informed consent

Exclusion Criteria:

  1. Unable to comply with the protocol
  2. Evidence of central nervous metastases
  3. Presence of life-threatening visceral metastases
  4. Corrected QT interval (QTc) >500millliseconds at screening
  5. Recent history of cardiac disease, including myocardial infarction, unstable angina pectoris or uncontrolled arrhythmia within 6 months prior to screening; or evidence of severe congestive heart failure with New York Heart Association severity classification > class I.
  6. Recent history of trombo-embolic events within 6 months prior to screening
  7. Hepatic impairment (Child-Pugh Class B or C)
  8. Severe concurrent disease, infection, co morbid condition that, in the judgment of the investigator would make the patient inappropriate for enrollment
  9. The concomitant use of strong CYP3A4 inhibitors (see table 1)
  10. Previous anti-androgen treatment
  11. Concurrent use of ER-directed anti hormonal therapies
  12. Radiotherapy or major surgery within 4 weeks before baseline PET scanning

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients
At day 0 before start with bicalutamide, a FDHT-PET/CT will be performed, and one after 6 weeks (i.e. 2 weeks after steady-state). The second FDHT-PET will be performed to determine if this scan can be used as a biomarker for early response. Patients will be treated with bicalutamide until progression or unacceptable toxicity is encountered.
Drug: Bicalutamide
150mg
Other Names:
  • casodex
Procedure: FDHT PET
PET scan
Other Names:
  • 18F-FDHT PET

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
quantify residual AR binding sites in metastatic breast cancer
Time Frame: 6 weeks
To quantify residual AR binding sites in metastatic breast cancer after 6 weeks of treatment with bicalutamide.
6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
determine whether changes in 18F-FDHT uptake
Time Frame: 6 weeks
To determine whether changes in 18F-FDHT uptake after 6 weeks associates with response to bicalutamide.
6 weeks
Influence amount of AR tumor expression
Time Frame: 6 weeks
To determine whether 18F-FDHT tracer uptake is influenced by the amount of AR tumor expression.
6 weeks
Difference in changes in AR availability
Time Frame: 6 weeks
To determine whether changes in AR availability are different for breast cancer subgroups during treatment with bicalutamide
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Investigators

  • Principal Investigator: Carolien P. Schröder, MD, PhD, University Medical Center Groningen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2016

Primary Completion (Actual)

November 25, 2019

Study Completion (Actual)

November 25, 2019

Study Registration Dates

First Submitted

August 25, 2015

First Submitted That Met QC Criteria

February 25, 2016

First Posted (Estimate)

March 3, 2016

Study Record Updates

Last Update Posted (Actual)

November 27, 2019

Last Update Submitted That Met QC Criteria

November 26, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL2015.0704

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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