FDHT PET and Bicalutamide in Metastatic Breast Cancer

NCT02697032 | Completed Phase 2 DMC

• 1 other identifier: NL2015.0704
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

FDHT; PET; Breast cancer; Bicalutamide

Outcome Measures

Primary Outcomes (1)

• quantify residual AR binding sites in metastatic breast cancer

  To quantify residual AR binding sites in metastatic breast cancer after 6 weeks of treatment with bicalutamide.

  6 weeks

Secondary Outcomes (3)

• determine whether changes in 18F-FDHT uptake

  6 weeks

• Influence amount of AR tumor expression

  6 weeks

• Difference in changes in AR availability

  6 weeks

Study Arms (1)

Patients

EXPERIMENTAL

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; Procedure: FDHT PET

Interventions

Bicalutamide DRUG

150mg

Also known as: casodex

Patients

FDHT PET PROCEDURE

PET scan

Also known as: 18F-FDHT PET

Patients

Eligibility Criteria

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

You may qualify if:

• 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)
• Tumor progression after at least one line of systemic treatment
• Measurable disease according to RECIST 1.1; or evaluable disease
• Age ≥ 18 years
• 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
• 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

You may not qualify if:

• Unable to comply with the protocol
• Evidence of central nervous metastases
• Presence of life-threatening visceral metastases
• Corrected QT interval (QTc) \>500millliseconds at screening
• 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.
• Recent history of trombo-embolic events within 6 months prior to screening
• Hepatic impairment (Child-Pugh Class B or C)
• Severe concurrent disease, infection, co morbid condition that, in the judgment of the investigator would make the patient inappropriate for enrollment
• The concomitant use of strong CYP3A4 inhibitors (see table 1)
• Previous anti-androgen treatment
• Concurrent use of ER-directed anti hormonal therapies
• Radiotherapy or major surgery within 4 weeks before baseline PET scanning

Sponsors & Collaborators

• University Medical Center Groningen: lead

Study Sites (1)

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Related Publications (1)

• Boers J, Venema CM, de Vries EFJ, Hospers GAP, Boersma HH, Rikhof B, Dorbritz C, Glaudemans AWJM, Schroder CP. Serial [18F]-FDHT-PET to predict bicalutamide efficacy in patients with androgen receptor positive metastatic breast cancer. Eur J Cancer. 2021 Feb;144:151-161. doi: 10.1016/j.ejca.2020.11.008. Epub 2020 Dec 18.

  PMID: 33341447 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

bicalutamide

Condition Hierarchy (Ancestors)

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

Study Officials

• Carolien P. Schröder, MD, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: March 3, 2016
• Study Start: February 1, 2016
• Primary Completion: November 25, 2019
• Study Completion: November 25, 2019
• Last Updated: November 27, 2019

Record last verified: 2019-11

Locations

NL (1)