Breast Neoplasms
Conditions
Keywords
dose-escalation, safety, dose-limiting toxicity
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).
Interventions
DRUGEstetrol
Estetrol formulated in tablets, in escalating doses, will be investigated in patients with estrogen receptor positive (ER+) locally advanced or metastatic breast cancer.
Sponsors
Pantarhei Oncology B.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The number of patients with a dose limiting toxicity (DLT) | 4 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Questionnaire on estrogen deficiency symptoms | 12 weeks | Quality of Life will be assessed by means of a questionnaire on estrogen deficiency symptoms. |
| Pharmacokinetics: estetrol trough levels | 2 weeks, 4 weeks, 8 weeks | — |
| Preliminary anti-tumour response according to RECIST 1.1 | 12 weeks | — |
Other
| Measure | Time frame |
|---|---|
| Number of patients with Adverse Events (AEs) | 12 weeks |
Countries
Germany
Outcome results
None listed