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

NCT ID: NCT02718144

Last Updated: 2021-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-01
• Study Completion Date: 2019-12-31

Brief Summary

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).

Conditions

Breast Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

estetrol

3 + 3 design with inter-patient dose escalation

Group Type: EXPERIMENTAL

Estetrol

Intervention Type: DRUG

Estetrol formulated in tablets, in escalating doses, will be investigated in patients with estrogen receptor positive (ER+) locally advanced or metastatic breast cancer.

Interventions

Estetrol

Estetrol formulated in tablets, in escalating doses, will be investigated in patients with estrogen receptor positive (ER+) locally advanced or metastatic breast cancer.

Intervention Type: DRUG

Eligibility Criteria

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.

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Pantarhei Oncology B.V.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Katholisches Klinikum Mainz

Mainz, , Germany

Universitatsmedizin Mainz

Mainz, , Germany

Countries

Germany

References

Singer CF, Bennink HJ, Natter C, Steurer S, Rudas M, Moinfar F, Appels N, Visser M, Kubista E. Antiestrogenic effects of the fetal estrogen estetrol in women with estrogen-receptor positive early breast cancer. Carcinogenesis. 2014 Nov;35(11):2447-51. doi: 10.1093/carcin/bgu144. Epub 2014 Jul 5.

Reference Type: RESULT

PMID: 24997853 (View on PubMed)

Visser M, Kloosterboer HJ, Bennink HJ. Estetrol prevents and suppresses mammary tumors induced by DMBA in a rat model. Horm Mol Biol Clin Investig. 2012 Apr 1;9(1):95-103. doi: 10.1515/hmbci-2012-0015.

Reference Type: RESULT

PMID: 25961355 (View on PubMed)

Other Identifiers

PR3106

Identifier Type: -

Identifier Source: org_study_id