Assessment of Safety and Efficacy of Estetrol in Postmenopausal Women With Advanced Estrogen Receptor Positive (ER+) Breast Cancer

June 16, 2021 updated by: Pantarhei Oncology B.V.

A Phase I/II Clinical Trial Assessing Safety and Efficacy of Estetrol (E4) in Postmenopausal Women With Advanced Estrogen Receptor Positive (ER+) Breast Cancer

This is a multi-center, open-label, phase I/IIa trial, dose-escalation study with a 3 + 3 cohort design to determine the recommended dose of estetrol for the treatment of patients with advanced breast cancer. After completing phase I part of the study (i.e. 4 weeks of treatment), patients will receive further treatment for 8 weeks at their individual phase I dose level (phase IIa part of the study).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2
  • Phase 1

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

  • Germany
      • Mainz, Germany
        • Katholisches Klinikum Mainz
      • Mainz, Germany
        • Universitatsmedizin Mainz

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

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Postmenopausal women with ER-positive and HER2-negative locally advanced and/or metastatic breast cancer, who progressed on standard therapies or for whom standard therapies are intolerant;
  • Patients should have experienced a natural or surgical menopause at least 5 years ago;
  • Failure of anti-estrogen treatment with tamoxifen and aromatase inhibitor(s) due to the development of resistance or unacceptable side effects with this treatment;
  • No undiagnosed vaginal bleeding;
  • No treatment with fulvestrant within 6 months of start of treatment;
  • Life expectancy at least 6 months;
  • Tumour assessment (CT scan) before the start of the E4 treatment;
  • Body mass index (BMI) between (≥) 18 and (≤) 35 kg/m2;
  • Able to swallow an oral medication;
  • Acceptable values of hematological parameters, liver and kidney function and calcium levels;
  • Acceptable values of hemostasis parameters (as of second cohort);
  • Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-2 (as of second cohort);
  • Reasonable physical and mental health as judged by the investigator and determined by physical examination, clinical laboratory assessments and vital signs;
  • Willing to give informed consent in writing.

Exclusion Criteria:

  • Uncontrolled nausea, vomiting, or diarrhea;
  • History of venous or arterial thromboembolic disease or a known defect in the blood coagulation system;
  • History of severe cardiac events or life threatening cardiac dysrhythmia (as of second cohort);
  • Patients who have unstable angina or clinical congestive heart failure (as of second cohort);
  • Uncontrolled hypertension, i.e. systolic blood pressure 160 mmHg and/or diastolic blood pressure 100 mmHg in the last 6 months with or without medication;
  • Diabetes mellitus with poor glycaemic control in the last 6 months (HbA1c above 7.5%);
  • Any other serious disease including systemic lupus erythematosus and untreated cholelithiasis;
  • Smoking >10 cigarettes/day;
  • Use of any other cancer therapy including radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, chemotherapy, or use of other investigational agents at the start of treatment.

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: OTHER
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: estetrol
3 + 3 design with inter-patient dose escalation
Drug: Estetrol
Estetrol formulated in tablets, in escalating doses, will be investigated in patients with estrogen receptor positive (ER+) locally advanced or metastatic breast cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The number of patients with a dose limiting toxicity (DLT)
Time Frame: 4 weeks
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Questionnaire on estrogen deficiency symptoms
Time Frame: 12 weeks
Quality of Life will be assessed by means of a questionnaire on estrogen deficiency symptoms.
12 weeks
Pharmacokinetics: estetrol trough levels
Time Frame: 2 weeks, 4 weeks, 8 weeks
2 weeks, 4 weeks, 8 weeks
Preliminary anti-tumour response according to RECIST 1.1
Time Frame: 12 weeks
12 weeks

Other Outcome Measures

Outcome Measure
Time Frame
Number of patients with Adverse Events (AEs)
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

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

Sponsor

Pantarhei Oncology B.V.

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)

June 1, 2017

Primary Completion (ACTUAL)

December 31, 2019

Study Completion (ACTUAL)

December 31, 2019

Study Registration Dates

First Submitted

March 2, 2016

First Submitted That Met QC Criteria

March 18, 2016

First Posted (ESTIMATE)

March 24, 2016

Study Record Updates

Last Update Posted (ACTUAL)

June 18, 2021

Last Update Submitted That Met QC Criteria

June 16, 2021

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PR3106

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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