Breast CancerPhase 2NCT03192293
Metformin and Simvastatin in Addition to Fulvestrant
A Phase 2 study testing Metformin/Simvastatin/Fulvestrant in people with Breast Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
This is a prospective single arm open-label Phase 2 study utilising the combination of Fulvestrant, Metformin and Simvastatin in post-menopausal ER-positive metastatic breast cancer, with the primary endpoint being Clinical Benefit Rate (defined as complete response, partial response or stable disease, equal to or… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Metformin/Simvastatin/Fulvestrant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteSingapore
- Study dates
- 20 Jan 2017to 20 Jan 2019
- Phase
- Phase 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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Prior treatment with any CDK inhibitor, Fulvestrant, Everolimus, or agent that inhibits the PI3K-mTOR pathway
- Patients with symptomatic visceral disease, or known uncontrolled or symptomatic CNS metastases
- Patients who have not yet recovered from the toxicities of the previous anti-cancer therapy.
- Concurrent administration of other anti-tumor therapies, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy are prohibited. Concomitant bone-modifying agents and gonadotropin-releasing hormone therapy are allowed.
- Major surgery or radiotherapy within 2 weeks of randomization
- Prior stem cell or bone marrow transplantation
Show all 13Show fewer
- Use of potent CYP3A4 inhibitors or inducers (Table 1); a washout period of 14 days is required for patients discontinuing these medications prior to study enrollment.
- Currently on medications for diabetes (e.g. Metformin, sulphonylureas, insulin) or hypercholesterolaemia (statins or fibrates)
- Renal impairment: Estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2
- Hepatic impairment: Aspartate transaminase (AST), Alanine Transaminase(ALT) ≥ 2.5 x upper limit of normal range (ULN), OR Total bilirubin ≥ 1.5 x ULN (subjects with Gilbert's syndrome can have bilirubin of up to 1.5 x ULN)
- Pregnancy.
- Breast feeding.
- Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital Singapore
Singapore, 119228
About this study
Official title: Single Arm Phase 2 Study of Metformin and Simvastatin in Addition to Fulvestrant in Metastatic Estrogen Receptor Positive Breast Cancer
This is a prospective single arm open-label Phase 2 study utilising the combination of Fulvestrant, Metformin and Simvastatin in post-menopausal ER-positive metastatic breast cancer, with the primary endpoint being Clinical Benefit Rate (defined as complete response, partial response or stable disease, equal to or more than 24 weeks). The hypothesis is that the addition of Metformin and Simvastatin to Fulvestrant will improve the Clinical Benefit Rate from 40% (historical data from control arm of PALOMA-3 study) to 60%. A total of 28 patients will be enrolled over a period of 24 months. Eligible patients will receive 500 mg Fulvestrant by intramuscular injection on days 1 and 15 of cycle one and then on day one of each subsequent cycle (28 days). Patients will be given 850mg oral Metformin twice-a-day (based on xenograft models which showed that Metformin had anti-tumor effects at a minimum dose of 1500mg per day), and 20mg oral Simvastatin every night (drawing reference from the investigators' group's window-of-opportunity study), daily throughout the cycle. As part of the in-build safety and tolerability design, all patients will have a lead-in period of 7 days where they receive 850mg oral Metformin twice-a-day and 20mg oral Simvastatin every night. Special adverse events of interest include lactic acidosis, diarrhea, bloatedness, transaminitis and rhabdomyolysis. If no dose-limiting toxic effects (DLT) occur, Fulvestrant will be commenced, and considered the start of cycle 1. If DLT occurs in any of the patients, the combination of Metformin and Simvastatin will be modified for the affected patient as per protocol, with further monitoring for another 7 days. This combination will be deemed safe for that patient if no DLT occurs, following which cycle 1 can officially commence.
At the time of study entry, blood samples will be drawn to establish baseline physiological parameters including fasting insulin, glucose, lipids and Homeostasis Model Assessment 2 (HOMA2). In patients who have accessible tumor sites and are willing to provide tissue for translational research, pre- and post-treatment (at end of 8 weeks) biopsies will be taken for correlative biomarker studies. Patients will be evaluated on an 8-weekly basis for toxicities and efficacy assessments during the first 6 months of treatment, followed by 12-weekly thereafter until disease progression, unacceptable toxicities, or patient withdrawal.
Read the detailed description
Endocrine therapy and acquired endocrine resistance in advanced breast cancer:
First-line treatment of metastatic estrogen receptor (ER) positive breast cancer with endocrine therapy such as Tamoxifen or aromatase inhibitors (AI) is efficacious, but development of secondary resistance is inevitable with median progression free survival of 9 months.1 Acquired resistance can be contributed by molecular cross-talk between estrogen receptors and other key survival and proliferative pathways. In particular, the PI3K/Akt/MAP kinase signaling pathway is upregulated with prolonged estrogen deprivation and is an important feature of progressive disease biology.2
The BOLERO-2 study showed an improvement in response rates and progression free survival with the addition of Everolimus, an mTOR-inhibitor to Exemestane in metastatic ER-positive breast cancer after failure on a non-steroidal AI.3 Synergy was also seen in a Phase 2 clinical trial with the combination of Fulvestrant and Everolimus in the second line setting.4 However, the clinical experience with Everolimus has been poor, with frequent adverse effects rendering the combination with endocrine therapy highly toxic. More recently, the PALOMA-1/3 studies have showed that targeting the CDK4/CDK6/E2F axis with Palbociclib is a feasible strategy with marked improvements in clinical endpoints when combined with Letrozole in the first line, and Fulvestrant after AI-failure.5,6 While the therapy was reasonably well-tolerated, Palbociclib remains prohibitively expensive, and is not widely used in countries where healthcare systems do not cover the cost of this novel combination.
Potential of Metformin and Simvastatin as anti-cancer agents:
It has been widely recognized that Metformin and Simvastatin, both commonly used medications in diabetes mellitus and dyslipidemia, have anti-cancer properties. Years of experience in the real world have shown that at standard doses, these 2 drugs can be used in combination with little toxicities. Metformin, a biguanide, results in activation of AMPK which consequently inhibits mTOR through phosphorylation of TSC2, as well as anti-proliferative effects through reduction in insulin receptor mediated mitogenesis and inhibition of cyclin dependent kinases.7,8 Pre-clinical studies in mouse xenograft models showed that at an equivalent dose of at least 1500mg per day, Metformin reduced the effective dosage of standard chemotherapeutic agents, and had preferential effects on tumor cells.9 Studies of Metformin in MCF7, an ER-positive breast cancer cell line, also showed that it resulted in significant reduction in protein synthesis as well as inhibition of the mTOR pathway.10 Simvastatin, a lipophilic HMGCoA reductase inhibitor, has been shown to interrupt oncogenic signaling by prenylation-dependent proteins including the RAS oncogene family, and attenuate PI3K signaling. In a recent window-of-opportunity study by the inverstigators' group, the investigators showed that at the usual prescribed dose of Simvastatin (20mg), a short course of therapy resulted in evident apoptosis and de-activation of the PI3K/Akt/mTOR and MAPK/ERK pathways in both clinical specimens as well as breast cancer cell lines.12
The investigators believe that there is untapped potential in the usage of Metformin and Simvastatin in targeting the PI3K/Akt/mTOR pathway which is upregulated in metastatic ER-positive breast cancer after progression on first-line endocrine therapy, and that this inexpensive and non-toxic combination will show synergy with Fulvestrant in the second-line (and beyond) setting.
- Conditions
- Breast Cancer
- Being tested
- Metformin/Simvastatin/Fulvestrant
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin/Simvastatin/FulvestrantDrug
7 days Lead-in period: Metformin: 850mg (one tablet) twice a day Simvastatin: 20mg (one tablet) once every night
Once the doctor has deemed that patients have tolerated Simvastatin and Metformin well, patients will receive Fulvestrant at standard doses:
Cycle 1: 500mg (in the form of two injections, 1 in each buttock) at Day 1 and Day 15. Each cycle comprises of 28 consecutive days starting from Day 1.
Cycle 2 and beyond: 500mg at Day 1 of each 28-day cycle.
Tumour biopsy at 8 weeks. Every 8 weeks for the first 6 months, every 12 weeks thereafter:
Performance status evaluation Medical history and physical examination Clinical tumor measurement Review of treatment-related side-effects Blood taking for research purpose and routine blood tests Routine scans
| Study group | Role | What they receive |
|---|---|---|
| Metformin/Simvastatin/Fulvestrant | Experimental | 7 days Lead-in period:
1. Metformin: 850mg (one tablet) twice a day
2. Simvastatin: 20mg (one tablet) once every night
Once the doctor has deemed that patients have tolerated Simvastatin and Metformin well, patients will receive Fulvestrant at standard doses:
1. Cycle 1: 500mg (in the form of two injections, 1 in each buttock) at Day 1 and Day 15. Each cycle comprises of 28 consecutive days starting from Day 1.
2. Cycle 2 and beyond: 500mg at Day 1 of each 28-day cycle. Receives: Drug: Metformin/Simvastatin/Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical benefit rate (CBR)
the percentage achieving CR, PR and SD in patients with measurable disease or the absence of disease progression in patients with non-measurable disease, lasting at least 24 weeks.
Measured: The Clinical Benefit Rate will be assessed at 24 weeks of treatment with study drug. The time frame will be through study completion, in an average of 2 years.
Secondary outcomes (3)
Objective response rates (ORR)
a best overall response of CR or PR.
Measured: The Objective Response Rate will be assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion, in an average of 2 years.
Progression-free survival (PFS)
the time from the date of study enrollment until the first date of documented disease progression or death due to any cause, whichever occurs first.
Measured: The progression-free survival will be assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion, in an average of 2 years.
Presence of toxicities
as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0.
Measured: The presence of toxicies will be monitored through study completion, in an average of 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2017
- Study start20 Jan 2017
- Primary completion20 Jan 2019 (estimated)
- Study completion20 Jan 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samuel Ow, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03192293
- Sponsor's protocol ID
- BR03/10/16
- Other IDs
- 2016/01178, 2016
- Status last verified
- Jan 2017
- First submitted
- 6 Feb 2017
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Park IH, Ro J, Lee KS, Kim EA, Kwon Y, Nam BH, Jung SY, Lee S, Kim SW, Kang HS. Phase II parallel group study showing comparable efficacy between premenopausal metastatic breast cancer patients treated with letrozole plus goserelin and postmenopausal patients treated with letrozole alone as first-line hormone therapy. J Clin Oncol. 2010 Jun 1;28(16):2705-11. doi: 10.1200/JCO.2009.26.5884. Epub 2010 Apr 26.
PubMed 20421538Miller TW, Balko JM, Arteaga CL. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J Clin Oncol. 2011 Nov 20;29(33):4452-61. doi: 10.1200/JCO.2010.34.4879. Epub 2011 Oct 17.
PubMed 22010023Massarweh S, Romond E, Black EP, Van Meter E, Shelton B, Kadamyan-Melkumian V, Stevens M, Elledge R. A phase II study of combined fulvestrant and everolimus in patients with metastatic estrogen receptor (ER)-positive breast cancer after aromatase inhibitor (AI) failure. Breast Cancer Res Treat. 2014 Jan;143(2):325-32. doi: 10.1007/s10549-013-2810-9. Epub 2013 Dec 11.
PubMed 24327334
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Arm Phase 2 Study of Metformin and Simvastatin in Addition to Fulvestrant in Metastatic Estrogen Receptor Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT03192293
- Acronym / sponsor ID
- BR03/10/16
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 20 Jan 2017 (actual)
- Primary completion
- 20 Jan 2019 (estimated)
- Study completion
- 20 Jan 2019 (estimated)
- First posted
- 20 Jun 2017 (actual)
- 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 prospective single arm open-label Phase 2 study utilising the combination of Fulvestrant, Metformin and Simvastatin in post-menopausal ER-positive metastatic breast cancer, with the primary endpoint being Clinical Benefit Rate (defined as complete response, partial response or stable disease, equal to or more than 24 weeks). The hypothesis is that the addition of Metformin and Simvastatin to Fulvestrant will improve the Clinical Benefit Rate from 40% (historical data from control arm of PALOMA-3 study) to 60%. A total of 28 patients will be enrolled over a period of 24 months. Eligible patients will receive 500 mg Fulvestrant by intramuscular injection on days 1 and 15 of cycle one and then on day one of each subsequent cycle (28 days). Patients will be given 850mg oral Metformin twice-a-day (based on xenograft models which showed that Metformin had anti-tumor effects at a minimum dose of 1500mg per day), and 20mg oral Simvastatin every night (drawing reference from the investigators' group's window-of-opportunity study), daily throughout the cycle. As part of the in-build safety and tolerability design, all patients will have a lead-in period of 7 days where they receive 850mg oral Metformin twice-a-day and 20mg oral Simvastatin every night. Special adverse events of interest include lactic acidosis, diarrhea, bloatedness, transaminitis and rhabdomyolysis. If no dose-limiting toxic effects (DLT) occur, Fulvestrant will be commenced, and considered the start of cycle 1. If DLT occurs in any of the patients, the combination of Metformin and Simvastatin will be modified for the affected patient as per protocol, with further monitoring for another 7 days. This combination will be deemed safe for that patient if no DLT occurs, following which cycle 1 can officially commence.
At the time of study entry, blood samples will be drawn to establish baseline physiological parameters including fasting insulin, glucose, lipids and Homeostasis Model Assessment 2 (HOMA2). In patients who have accessible tumor sites and are willing to provide tissue for translational research, pre- and post-treatment (at end of 8 weeks) biopsies will be taken for correlative biomarker studies. Patients will be evaluated on an 8-weekly basis for toxicities and efficacy assessments during the first 6 months of treatment, followed by 12-weekly thereafter until disease progression, unacceptable toxicities, or patient withdrawal.
Detailed description
Endocrine therapy and acquired endocrine resistance in advanced breast cancer:
First-line treatment of metastatic estrogen receptor (ER) positive breast cancer with endocrine therapy such as Tamoxifen or aromatase inhibitors (AI) is efficacious, but development of secondary resistance is inevitable with median progression free survival of 9 months.1 Acquired resistance can be contributed by molecular cross-talk between estrogen receptors and other key survival and proliferative pathways. In particular, the PI3K/Akt/MAP kinase signaling pathway is upregulated with prolonged estrogen deprivation and is an important feature of progressive disease biology.2
The BOLERO-2 study showed an improvement in response rates and progression free survival with the addition of Everolimus, an mTOR-inhibitor to Exemestane in metastatic ER-positive breast cancer after failure on a non-steroidal AI.3 Synergy was also seen in a Phase 2 clinical trial with the combination of Fulvestrant and Everolimus in the second line setting.4 However, the clinical experience with Everolimus has been poor, with frequent adverse effects rendering the combination with endocrine therapy highly toxic. More recently, the PALOMA-1/3 studies have showed that targeting the CDK4/CDK6/E2F axis with Palbociclib is a feasible strategy with marked improvements in clinical endpoints when combined with Letrozole in the first line, and Fulvestrant after AI-failure.5,6 While the therapy was reasonably well-tolerated, Palbociclib remains prohibitively expensive, and is not widely used in countries where healthcare systems do not cover the cost of this novel combination.
Potential of Metformin and Simvastatin as anti-cancer agents:
It has been widely recognized that Metformin and Simvastatin, both commonly used medications in diabetes mellitus and dyslipidemia, have anti-cancer properties. Years of experience in the real world have shown that at standard doses, these 2 drugs can be used in combination with little toxicities. Metformin, a biguanide, results in activation of AMPK which consequently inhibits mTOR through phosphorylation of TSC2, as well as anti-proliferative effects through reduction in insulin receptor mediated mitogenesis and inhibition of cyclin dependent kinases.7,8 Pre-clinical studies in mouse xenograft models showed that at an equivalent dose of at least 1500mg per day, Metformin reduced the effective dosage of standard chemotherapeutic agents, and had preferential effects on tumor cells.9 Studies of Metformin in MCF7, an ER-positive breast cancer cell line, also showed that it resulted in significant reduction in protein synthesis as well as inhibition of the mTOR pathway.10 Simvastatin, a lipophilic HMGCoA reductase inhibitor, has been shown to interrupt oncogenic signaling by prenylation-dependent proteins including the RAS oncogene family, and attenuate PI3K signaling. In a recent window-of-opportunity study by the inverstigators' group, the investigators showed that at the usual prescribed dose of Simvastatin (20mg), a short course of therapy resulted in evident apoptosis and de-activation of the PI3K/Akt/mTOR and MAPK/ERK pathways in both clinical specimens as well as breast cancer cell lines.12
The investigators believe that there is untapped potential in the usage of Metformin and Simvastatin in targeting the PI3K/Akt/mTOR pathway which is upregulated in metastatic ER-positive breast cancer after progression on first-line endocrine therapy, and that this inexpensive and non-toxic combination will show synergy with Fulvestrant in the second-line (and beyond) setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin/Simvastatin/Fulvestrant | Experimental | Drug: Metformin/Simvastatin/Fulvestrant7 days Lead-in period: 1. Metformin: 850mg (one tablet) twice a day 2. Simvastatin: 20mg (one tablet) once every night Once the doctor has deemed that patients have tolerated Simvastatin and Metformin well, patients will receive Fulvestrant at standard doses: 1. Cycle 1: 500mg (in the form of two injections, 1 in each buttock) at Day 1 and Day 15. Each cycle comprises of 28 consecutive days starting from Day 1. 2. Cycle 2 and beyond: 500mg at Day 1 of each 28-day cycle. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (13 listed)
- Prior treatment with any CDK inhibitor, Fulvestrant, Everolimus, or agent that inhibits the PI3K-mTOR pathway
- Patients with symptomatic visceral disease, or known uncontrolled or symptomatic CNS metastases
- Patients who have not yet recovered from the toxicities of the previous anti-cancer therapy.
- Concurrent administration of other anti-tumor therapies, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy are prohibited. Concomitant bone-modifying agents and gonadotropin-releasing hormone therapy are allowed.
- Major surgery or radiotherapy within 2 weeks of randomization
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 |
|---|---|---|
| Metformin/Simvastatin/Fulvestrant7 days Lead-in period: Metformin: 850mg (one tablet) twice a day Simvastatin: 20mg (one tablet) once every night Once the doctor has deemed that patients have tolerated Simvastatin and Metformin well, patients will receive Fulvestrant at standard doses: Cycle 1: 500mg (in the form of two injections, 1 in each buttock) at Day 1 and Day 15. Each cycle comprises of 28 consecutive days starting from Day 1. Cycle 2 and beyond: 500mg at Day 1 of each 28-day cycle. Tumour biopsy at 8 weeks. Every 8 weeks for the first 6 months, every 12 weeks thereafter: Performance status evaluation Medical history and physical examination Clinical tumor measurement Review of treatment-related side-effects Blood taking for research purpose and routine blood tests Routine scans | Drug | Metformin/Simvastatin/Fulvestrant |
Primary outcome
Clinical benefit rate (CBR)
Time frame: The Clinical Benefit Rate will be assessed at 24 weeks of treatment with study drug. The time frame will be through study completion, in an average of 2 years.
the percentage achieving CR, PR and SD in patients with measurable disease or the absence of disease progression in patients with non-measurable disease, lasting at least 24 weeks.
3 secondary outcomes
Objective response rates (ORR)
Time frame: The Objective Response Rate will be assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion, in an average of 2 years.
Progression-free survival (PFS)
Time frame: The progression-free survival will be assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed through study completion, in an average of 2 years.
Presence of toxicities
Time frame: The presence of toxicies will be monitored through study completion, in an average of 2 years.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Results publication: PubMed 20421538Park IH, Ro J, Lee KS, Kim EA, Kwon Y, Nam BH, Jung SY, Lee S, Kim SW, Kang HS. Phase II parallel group study showing comparable efficacy between premenopausal metastatic breast cancer patients treated with letrozole plus goserelin and postmenopausal patients treated with letrozole alone as first-line hormone therapy. J Clin Oncol. 2010 Jun 1;28(16):2705-11. doi: 10.1200/JCO.2009.26.5884. Epub 2010 Apr 26.
- Results publication: PubMed 22010023Miller TW, Balko JM, Arteaga CL. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J Clin Oncol. 2011 Nov 20;29(33):4452-61. doi: 10.1200/JCO.2010.34.4879. Epub 2011 Oct 17.
- Results publication: PubMed 24327334Massarweh S, Romond E, Black EP, Van Meter E, Shelton B, Kadamyan-Melkumian V, Stevens M, Elledge R. A phase II study of combined fulvestrant and everolimus in patients with metastatic estrogen receptor (ER)-positive breast cancer after aromatase inhibitor (AI) failure. Breast Cancer Res Treat. 2014 Jan;143(2):325-32. doi: 10.1007/s10549-013-2810-9. Epub 2013 Dec 11.
- Individual participant dataSharing planned: No
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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.
Samuel Ow principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin/Simvastatin/Fulvestrant in people with Breast Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
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 0 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. 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 phase mean?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Samuel Ow ((65) 6772- 5934, samuel_ow@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical benefit rate (CBR) (time frame: The Clinical Benefit Rate will be assessed at 24 weeks of treatment with study drug. The time frame will be through study completion, in an average of 2 years.). 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 NCT03192293, which also lists 3 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 20 Jun 2017.