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

NCT02718144 | Completed Phase 1 DMC

• 1 other identifier: PR3106
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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

Keywords

dose-escalation; safety; dose-limiting toxicity

Outcome Measures

Primary Outcomes (1)

• The number of patients with a dose limiting toxicity (DLT)

  4 weeks

Secondary Outcomes (3)

• Questionnaire on estrogen deficiency symptoms

  12 weeks

• Pharmacokinetics: estetrol trough levels

  2 weeks, 4 weeks, 8 weeks

• Preliminary anti-tumour response according to RECIST 1.1

  12 weeks

Other Outcomes (1)

• Number of patients with Adverse Events (AEs)

  12 weeks

Study Arms (1)

estetrol

EXPERIMENTAL

3 + 3 design with inter-patient dose escalation

Drug: Estetrol

Interventions

Estetrol DRUG

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

estetrol

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pantarhei Oncology B.V.: lead

Study Sites (2)

Katholisches Klinikum Mainz

Mainz, Germany

Location

Universitatsmedizin Mainz

Mainz, Germany

Location

Related 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: 10.1093/carcin/bgu144. Epub 2014 Jul 5.

  PMID: 24997853 RESULT

• 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.

  PMID: 25961355 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Estetrol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estriol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2016
• First Posted: March 24, 2016
• Study Start: June 1, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: June 18, 2021

Record last verified: 2019-11

Locations

DE (2)