Postmenopausal WomenPhase 2NCT01231659
Safety and Efficacy of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer
A Phase 2 study testing Everolimus and Letrozole in people with Postmenopausal Women and Locally Advanced Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 7 sites in Israel.
Trial summary
This was a multi-center, Israeli phase II open label study evaluating treatment with RAD001 (10 mg daily) combined with letrozole (2.5 mg daily) in postmenopausal women after recurrence or progression on Tamoxifen, Anastrozole or Examestane. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Postmenopausal Women, Locally Advanced Metastatic Breast Cancer, Metastatic Breast Cancer
- What is being tested?
- Everolimus and Letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 7 sitesIsrael
- Study dates
- 9 Aug 2011to 30 Apr 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer after documented recurrence or progression on Tamoxifen, Anastrozole or Examestane.
- Refractory disease to hormonal therapy is defined as:
- Recurrence while on, or within 12 month of end of, adjuvant treatment with Tamoxifen , Anastrozole, or Exemestane.
- Recurrence while on, or within 24 month of end of, adjuvant treatment with Letrozole.
- Progression while on Tamoxifen, Anastrozole or Exemestane treatment for locally advanced or metastatic breast cancer.
Who cannot join
- Prior use of chemotherapy and letrozole for Advanced Breast Cancer and mTOR inhibitors as the last anticancer treatment prior to study entry.
- Patients must have radiological evidence of recurrence or progression on last therapy prior to study entry.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Israel7 sites
Novartis Investigative Site
Jerusalem, 91120
Novartis Investigative Site
Kfar Saba, 4428164
Novartis Investigative Site
Petah Tikva, 49100
Novartis Investigative Site
Ramat Gan, 52621
Novartis Investigative Site
Rehovot, 76100
Novartis Investigative Site
Tel Aviv, 62439
Novartis Investigative Site
Tel Aviv, 6423906
About this study
Official title: Phase II Open Label Study of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic, Estrogen Receptor Positive Breast Cancer, After Failure of Tamoxifen and/or Anastrozole and/or Letrozole and/or Fulvestrant and/or Exemestane
This was a multi-center, Israeli phase II open label study evaluating treatment with RAD001 (10 mg daily) combined with letrozole (2.5 mg daily) in postmenopausal women after recurrence or progression on Tamoxifen, Anastrozole or Examestane.
There were no treatments specifically approved after recurrence or progression on AIs. Available options, based on common clinical practice and several treatment guidelines (e.g. NCCN treatment guidelines 2008), included fulvestrant.
Combining RAD001 with letrazole was a rational approach to the treatment of advanced Brest Cancer, offering the potential for inhibition of tumor cell growth\ proliferation and anti angiogenesis while at the same time potentially preventing the development of letrazole resistance.
Read the detailed description
Screening Period:
Postmenopausal women with estrogen receptor positive, locally advanced or metastatic breast cancer whose disease was refractory to hormonal therapy and had a documented recurrence or progression on last therapy for their breast cancer with either tamoxifen, anastrozole, letrozole, fulvestrant or exemestan were screened for eligibility within 28 days prior to treatment Day 1.
Treatment Period:
Patients started receiving everolimus (10 mg daily oral dose) combined with letrozole (2.5 mg daily oral dose) tablets from treatment Day 1. Study treatment continued until disease progression, intolerable toxicity or consent withdrawal. Dose adjustment (reduction, interruption or possible dose re-escalation to starting dose) could be done based on the safety findings. Tumor assessments were performed every 12 weeks until disease progression. In order to confirm response at least four weeks after first observation, additional scans to determine a complete response (CR) or partial response (PR) or stable disease (SD) were performed. Patients were followed for safety until 28 days after study treatment discontinuation.
Post Treatment Follow up for Survival:
Patients were followed for survival every 3 months for up to 3 years. Survival information could be obtained via phone and information was documented in the source documents.
- Being tested
- Everolimus, Letrozole
- Keywords
- RAD001 (Everolimus), Letrozole, Breast cancer, Metastatic Breast cancer, Estrogen receptor positive, Failure of Tamoxifen, Anastrozole or Examestane
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called RAD001
Everolimus 10 mg (2 tablets of 5 mg) once daily
LetrozoleDrug
Letrozole 2.5 mg once daily
| Study group | Role | What they receive |
|---|---|---|
| Everolimus + Letrozole | Experimental | All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol. Receives: Drug: Everolimus; Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Overall Response Rate (ORR)
Overall Response Rate (ORR) was defined as the proportion of patients whose best overall response was either complete response (CR) or partial response (PR) according to RECIST 1.0 for target lesions and assessed by CT: Complete Response (CR), disappearance of all target lesions for a period of at least one month; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (ORR) = CR + PR. Only descriptive statistics.
Measured: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 15 months
Secondary outcomes (4)
Median Time to Progression-Free Survival (PFS)
Progression Free Survival (PFS) was defined as the time from the date of study entry to the date of first documented tumor progression or death from any cause, whichever occurred first. If a patient did not have an event, PFS was censored at the last date of tumor assessment. For patients with measurable disease at baseline, progression was determined according to the RECIST 1.0 criteria. Only descriptive analysis done.
Measured: Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 66 months
Median Time to Overall Survival (OS)
Overall Survival (OS) was defined as the time from the date of study entry to date of death due to any cause. If a death had not observed by the date of analysis, then OS was censored at the date of last contact. Distribution of OS was estimated using the Kaplan Meier method. The median OS along with 95% CI was presented.
Measured: From Date of randomization up to approximately 66 months
Disease Control Rate (DCR)
Disease Control Rate (DCR) was defined as the proportion of patients whose best overall response was either: Complete Response (CR), Partial Response (PR) or Stable Disease (SD). Disease Control Rate was calculated only for patients with measurable disease at baseline and was summarized using descriptive statistics.
Measured: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 66 months
Long-term Safety and Tolerability
The assessment of safety was based mainly on the frequency of AEs and on the number of laboratory values that fell outside of pre-determined ranges. Other safety data (e.g. ECG, vital signs) were considered as appropriate. Only descriptive analysis done.
Measured: From Date of first dose up to approximately 66 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2010 (estimated)
- Study start9 Aug 2011
- Primary completion20 Nov 2012
- Study completion30 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Postmenopausal WomenStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01231659
- Sponsor's protocol ID
- CRAD001JIL05
- Status last verified
- Mar 2021
- First submitted
- 28 Oct 2010
- Last updated
- 26 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Open Label Study of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic, Estrogen Receptor Positive Breast Cancer, After Failure of Tamoxifen and/or Anastrozole and/or Letrozole and/or Fulvestrant and/or Exemestane
- ClinicalTrials.gov ID
- NCT01231659
- Acronym / sponsor ID
- CRAD001JIL05
- Keywords
- RAD001 (Everolimus), Letrozole, Breast cancer, Metastatic Breast cancer, Estrogen receptor positive, Failure of Tamoxifen, Anastrozole or Examestane
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 9 Aug 2011 (actual)
- Primary completion
- 20 Nov 2012 (actual)
- Study completion
- 30 Apr 2017 (actual)
- First posted
- 1 Nov 2010 (estimated)
- Results
- Posted 26 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a multi-center, Israeli phase II open label study evaluating treatment with RAD001 (10 mg daily) combined with letrozole (2.5 mg daily) in postmenopausal women after recurrence or progression on Tamoxifen, Anastrozole or Examestane.
There were no treatments specifically approved after recurrence or progression on AIs. Available options, based on common clinical practice and several treatment guidelines (e.g. NCCN treatment guidelines 2008), included fulvestrant.
Combining RAD001 with letrazole was a rational approach to the treatment of advanced Brest Cancer, offering the potential for inhibition of tumor cell growth\ proliferation and anti angiogenesis while at the same time potentially preventing the development of letrazole resistance.
Detailed description
Screening Period:
Postmenopausal women with estrogen receptor positive, locally advanced or metastatic breast cancer whose disease was refractory to hormonal therapy and had a documented recurrence or progression on last therapy for their breast cancer with either tamoxifen, anastrozole, letrozole, fulvestrant or exemestan were screened for eligibility within 28 days prior to treatment Day 1.
Treatment Period:
Patients started receiving everolimus (10 mg daily oral dose) combined with letrozole (2.5 mg daily oral dose) tablets from treatment Day 1. Study treatment continued until disease progression, intolerable toxicity or consent withdrawal. Dose adjustment (reduction, interruption or possible dose re-escalation to starting dose) could be done based on the safety findings. Tumor assessments were performed every 12 weeks until disease progression. In order to confirm response at least four weeks after first observation, additional scans to determine a complete response (CR) or partial response (PR) or stable disease (SD) were performed. Patients were followed for safety until 28 days after study treatment discontinuation.
Post Treatment Follow up for Survival:
Patients were followed for survival every 3 months for up to 3 years. Survival information could be obtained via phone and information was documented in the source documents.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus + Letrozole | Experimental | Drug: Everolimus, Drug: LetrozoleAll patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer after documented recurrence or progression on Tamoxifen, Anastrozole or Examestane.
Key exclusion criteria (2 listed)
- Prior use of chemotherapy and letrozole for Advanced Breast Cancer and mTOR inhibitors as the last anticancer treatment prior to study entry.
- Patients must have radiological evidence of recurrence or progression on last therapy prior to study entry.
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 |
|---|---|---|
| EverolimusAlso: RAD001Everolimus 10 mg (2 tablets of 5 mg) once daily | Drug | Everolimus + Letrozole |
| LetrozoleLetrozole 2.5 mg once daily | Drug | Everolimus + Letrozole |
Primary outcome
Percentage of Participants With Overall Response Rate (ORR)
Time frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 15 months
Overall Response Rate (ORR) was defined as the proportion of patients whose best overall response was either complete response (CR) or partial response (PR) according to RECIST 1.0 for target lesions and assessed by CT: Complete Response (CR), disappearance of all target lesions for a period of at least one month; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (ORR) = CR + PR. Only descriptive statistics.
4 secondary outcomes
Median Time to Progression-Free Survival (PFS)
Time frame: Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 66 months
Median Time to Overall Survival (OS)
Time frame: From Date of randomization up to approximately 66 months
Disease Control Rate (DCR)
Time frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 66 months
Long-term Safety and Tolerability
Time frame: From Date of first dose up to approximately 66 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus and Letrozole in people with Postmenopausal Women and Locally Advanced Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 7 sites in Israel.
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 5 inclusion and 2 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 26 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Israel. 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?
Yes. Results are posted in the registry (first posted 26 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Participants With Overall Response Rate (ORR) (time frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 15 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Mar 2021.