Breast NeoplasmsPhase 1/2NCT02718144
Assessment of Safety and Efficacy of Estetrol in Postmenopausal Women With Advanced Estrogen Receptor Positive (ER+) Breast Cancer
A Phase 1/2 study testing Estetrol in people with Breast Neoplasms, run by Pantarhei Oncology B.V. at 2 sites in Germany.
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. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Estetrol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesGermany
- Study dates
- 1 Jun 2017to 31 Dec 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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%);
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- 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.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Katholisches Klinikum Mainz
Mainz
Universitatsmedizin Mainz
Mainz
About this study
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
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
- Being tested
- Estetrol
- Keywords
- dose-escalation, safety, dose-limiting toxicity
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstetrolDrug
Estetrol formulated in tablets, in escalating doses, will be investigated in patients with estrogen receptor positive (ER+) locally advanced or metastatic breast cancer.
| Study group | Role | What they receive |
|---|---|---|
| estetrol | Experimental | 3 + 3 design with inter-patient dose escalation Receives: Drug: Estetrol |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of patients with a dose limiting toxicity (DLT)
Measured: 4 weeks
Secondary outcomes (3)
Questionnaire on estrogen deficiency symptoms
Quality of Life will be assessed by means of a questionnaire on estrogen deficiency symptoms.
Measured: 12 weeks
Pharmacokinetics: estetrol trough levels
Measured: 2 weeks, 4 weeks, 8 weeks
Preliminary anti-tumour response according to RECIST 1.1
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2016 (estimated)
- Study start1 Jun 2017
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pantarhei Oncology B.V.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02718144
- Sponsor's protocol ID
- PR3106
- Status last verified
- Nov 2019
- First submitted
- 2 Mar 2016
- Last updated
- 18 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 24997853Visser 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.
PubMed 25961355
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02718144
- Acronym / sponsor ID
- PR3106
- Conditions
- Breast Neoplasms
- Keywords
- dose-escalation, safety, dose-limiting toxicity
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Pantarhei Oncology B.V.University, hospital or other
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 24 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| estetrol | Experimental | Drug: Estetrol3 + 3 design with inter-patient dose escalation |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- 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;
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EstetrolEstetrol formulated in tablets, in escalating doses, will be investigated in patients with estrogen receptor positive (ER+) locally advanced or metastatic breast cancer. | Drug | estetrol |
Primary outcome
The number of patients with a dose limiting toxicity (DLT)
Time frame: 4 weeks
3 secondary outcomes
Questionnaire on estrogen deficiency symptoms
Time frame: 12 weeks
Pharmacokinetics: estetrol trough levels
Time frame: 2 weeks, 4 weeks, 8 weeks
Preliminary anti-tumour response according to RECIST 1.1
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2021.
- Results publication: PubMed 24997853Singer 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.
- Results publication: PubMed 25961355Visser 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Estetrol in people with Breast Neoplasms, run by Pantarhei Oncology B.V. at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of patients with a dose limiting toxicity (DLT) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02718144, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2021.