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

Breast Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02718144
• Other study ID #: PR3106
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 1, 2017
• Est. completion date: December 31, 2019

Study information

• Verified date: November 2019
• Source: Pantarhei Oncology B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Germany	Katholisches Klinikum Mainz	Mainz
Germany	Universitatsmedizin Mainz	Mainz

Sponsors (1)

Lead Sponsor	Collaborator
Pantarhei Oncology B.V.

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients with Adverse Events (AEs)		12 weeks
Primary	The number of patients with a dose limiting toxicity (DLT)		4 weeks
Secondary	Questionnaire on estrogen deficiency symptoms	Quality of Life will be assessed by means of a questionnaire on estrogen deficiency symptoms.	12 weeks
Secondary	Pharmacokinetics: estetrol trough levels		2 weeks, 4 weeks, 8 weeks
Secondary	Preliminary anti-tumour response according to RECIST 1.1		12 weeks