Breast CancerPhase 2RADARNCT00466102
Efficacy of RAD001 in Breast Cancer Patients With Bone Metastases
A Phase 2 study testing RAD001 in people with Breast Cancer, run by GBG Forschungs GmbH at 1 site in Germany.
Trial summary
The purpose of this study is to determine wether RAD001 can inhibit growth of tumour cells and/or stop the formation and activity of bone degrading osteoclasts. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- RAD001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2006to Dec 2012
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- Histologically confirmed invasive adenocarcinoma of the breast.
- Primary tumour or metastasis negative or positive (≥ 10% positive stained cells) for oestrogen and/or progesterone receptor detected by immunohistochemistry.
- Single or multiple bone metastasis (x-ray, CT or MRI) as only metastatic site.
- Postmenopausal hormone receptor positive patients should have received an aromatase inhibitor in any given previous breast cancer therapy. Concurrent endocrine treatment for metastatic bone disease is obligatory. Previous treatment with bisphosphonates is allowed.
- Up to one previous chemotherapy for metastatic disease is allowed.
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- Patients must have either measurable or non-measurable target lesions according to the WHO criteria.
- At least 1 target lesion must be completely outside the radiation portal or there must be pathologic proof of progressive disease.
- At least 2 weeks since major surgery with full recovery.
- Complete staging within 4 weeks prior to registration.
- Karnofsky performance status evaluation > 60%.
- Age >18 years.
- Absolute neutrophil count >1,500 cells/µl, platelet count >100,000 cells/µl.
- Bilirubin >1.5x the upper normal limit for the institution (UNL); elevation of transaminases, alkaline phosphatase < 2.5x UNL and serum albumin < 30g/l. Normal renal function (creatinine >1.5x upper normal limit)
- If of childbearing potential, negative pregnancy test. In addition the patient has to agree to use an effective method to avoid pregnancy for the duration of the study.
Who cannot join
- Known hypersensitivity reaction to the compounds or incorporated substances (e.g. everolimus or sirolimus [rapamycin] or lactose).
- Concurrent immunotherapy or hormone replacement therapy and use of hormonal contraceptives.
- Need for chemotherapy or irradiation of bone metastasis during study treatment
- HER2 positive primary tumour and/or lesion
- Evidence of metastasis in other organs
- Uncompensated diabetes mellitus; fasting value of blood sugar of >120 (mg/dl)
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- Corrected (adjusted for serum albumin) serum calcium concentration < 8.0 mg/dl (2.00 mmol/l) or > 12.0 mg/dl (3.00 mmol/l)
- Abnormal renal function as evidenced by a calculated creatinine clearance < 30 ml/minute
- Life expectancy of less than 3 months
- Serious intercurrent medical or psychiatric illness that may interfere with the planned treatment (including AIDS and serious active infection).
- History of other malignancy within the last 5 years which could affect the diagnosis or assessment of metastatic breast cancer
- Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (e.g. rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole, ritonavir, telithromycin, erythromycin, verapamil, dilitazem) within the last 5 days or the expected need for these treatments during study participation.
- Pregnant or nursing women.
- The patient is not accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre which could be the Principal or Co-Investigator's site.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: RADAR: A Randomized Discontinuation Phase II Study to Determine the Efficacy of RAD001 in Breast Cancer Patients With Bone Metastases
The purpose of this study is to determine wether RAD001 can inhibit growth of tumour cells and/or stop the formation and activity of bone degrading osteoclasts.
Read the detailed description
RAD001 is an orally bioavailable and well tolerated rapamycin ester analogue, which acts by selectively inhibiting mTOR (mammalian target of rapamycin). mTor is an intracellular protein kinase implicated in the control of cellular proliferation in neoplastic cells. Treatment with RAD001 has been shown to inhibit these signalling events and leads to growth retardation of tumour cells. In addition RAD001 in vitro stops the formation and activity of osteoclasts. Therefore a therapy of advanced breast cancer with progressive bone metastases seems to be reasonable with RAD001.
Comparison:
All patients receive RAD001 in an 8 week run in phase. Patients who show a response after 8 weeks will continue receiving RAD001. All patients with stable disease after the run in phase will be randomised to receive either RAD001 or placebo and will be followed up until progression of disease. Patients with progressive disease after the 8 week run in phase will be withdrawn from the trial.
- Conditions
- Breast Cancer
- Being tested
- RAD001, Placebo
- Keywords
- Breast Cancer, Bone metastases as only metastatic site, Breast cancer, HER2 negative, Bone metastasis as only metastatic site, Pretreated with endocrine therapy, Up to one previous chemotherapy, Previous treatment with bisphosphonates allowed
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
Tablet of 5 mg, 2 tablets (10 mg) are taken once daily during study therapy
PlaceboDrug
2 tablets are taken once daily during study therapy
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Patients with stable disease after 8 week run in randomized to RAD001 (blinded) Receives: Drug: RAD001 |
| 2 | Placebo comparator | Patients with stable disease after 8 week run in receive placebo (blinded) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the time to progression (TTP) in patients with no change in bone metastases after an 8 week run in treatment with RAD001 compared to placebo
Measured: 40 weeks
Secondary outcomes (6)
To determine the objective response rate after 8 weeks of RAD001
Measured: 8 weeks
To determine the TTP in patients with a response after 8 weeks of RAD001
Measured: 8 weeks
To determine the overall clinical benefit defined as CR, PR or stable disease > 24 weeks for patients continuing RAD001 after the 8 week run in phase
Measured: 40 weeks
To evaluate the safety and toxicity of RAD001
Measured: 40 weeks
To assess the frequency of bone related events
Measured: 40 weeks
To assess changes of pain intensity during treatment
Measured: 40 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2007 (estimated)
- Study startDec 2006
- Primary completionDec 2010
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Nicolai Maass, MD, Prof., Principal investigator, Universitätsfrauenklinik Aachen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00466102
- Sponsor's protocol ID
- GBG 41
- Acronym
- RADAR
- Status last verified
- Aug 2012
- First submitted
- 25 Apr 2007
- Last updated
- 30 Aug 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RADAR: A Randomized Discontinuation Phase II Study to Determine the Efficacy of RAD001 in Breast Cancer Patients With Bone Metastases
- ClinicalTrials.gov ID
- NCT00466102
- Acronym / sponsor ID
- RADAR / GBG 41
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, Bone metastases as only metastatic site, Breast cancer, HER2 negative, Bone metastasis as only metastatic site, Pretreated with endocrine therapy, Up to one previous chemotherapy, Previous treatment with bisphosphonates allowed
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Dec 2006
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2012 (estimated)
- First posted
- 27 Apr 2007 (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.
The purpose of this study is to determine wether RAD001 can inhibit growth of tumour cells and/or stop the formation and activity of bone degrading osteoclasts.
Detailed description
RAD001 is an orally bioavailable and well tolerated rapamycin ester analogue, which acts by selectively inhibiting mTOR (mammalian target of rapamycin). mTor is an intracellular protein kinase implicated in the control of cellular proliferation in neoplastic cells. Treatment with RAD001 has been shown to inhibit these signalling events and leads to growth retardation of tumour cells. In addition RAD001 in vitro stops the formation and activity of osteoclasts. Therefore a therapy of advanced breast cancer with progressive bone metastases seems to be reasonable with RAD001.
Comparison:
All patients receive RAD001 in an 8 week run in phase. Patients who show a response after 8 weeks will continue receiving RAD001. All patients with stable disease after the run in phase will be randomised to receive either RAD001 or placebo and will be followed up until progression of disease. Patients with progressive disease after the 8 week run in phase will be withdrawn from the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: RAD001Patients with stable disease after 8 week run in randomized to RAD001 (blinded) |
| 2 | Placebo comparator | Drug: PlaceboPatients with stable disease after 8 week run in receive placebo (blinded) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- Histologically confirmed invasive adenocarcinoma of the breast.
- Primary tumour or metastasis negative or positive (≥ 10% positive stained cells) for oestrogen and/or progesterone receptor detected by immunohistochemistry.
- Single or multiple bone metastasis (x-ray, CT or MRI) as only metastatic site.
- Postmenopausal hormone receptor positive patients should have received an aromatase inhibitor in any given previous breast cancer therapy. Concurrent endocrine treatment for metastatic bone disease is obligatory. Previous treatment with bisphosphonates is allowed.
Key exclusion criteria (15 listed)
- Known hypersensitivity reaction to the compounds or incorporated substances (e.g. everolimus or sirolimus [rapamycin] or lactose).
- Concurrent immunotherapy or hormone replacement therapy and use of hormonal contraceptives.
- Need for chemotherapy or irradiation of bone metastasis during study treatment
- HER2 positive primary tumour and/or lesion
- Evidence of metastasis in other organs
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 |
|---|---|---|
| RAD001Tablet of 5 mg, 2 tablets (10 mg) are taken once daily during study therapy | Drug | 1 |
| Placebo2 tablets are taken once daily during study therapy | Drug | 2 |
Primary outcome
To determine the time to progression (TTP) in patients with no change in bone metastases after an 8 week run in treatment with RAD001 compared to placebo
Time frame: 40 weeks
6 secondary outcomes
To determine the objective response rate after 8 weeks of RAD001
Time frame: 8 weeks
To determine the TTP in patients with a response after 8 weeks of RAD001
Time frame: 8 weeks
To determine the overall clinical benefit defined as CR, PR or stable disease > 24 weeks for patients continuing RAD001 after the 8 week run in phase
Time frame: 40 weeks
To evaluate the safety and toxicity of RAD001
Time frame: 40 weeks
To assess the frequency of bone related events
Time frame: 40 weeks
To assess changes of pain intensity during treatment
Time frame: 40 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2012.
- Related InfoLink provided by the sponsor.
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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.
Nicolai Maass, MD, Prof. principal investigator
Universitätsfrauenklinik Aachen
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 RAD001 in people with Breast Cancer, run by GBG Forschungs GmbH at 1 site 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 15 inclusion and 15 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 30 Aug 2012. 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 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. Some participants in this study may receive a placebo. 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?
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?
To determine the time to progression (TTP) in patients with no change in bone metastases after an 8 week run in treatment with RAD001 compared to placebo (time frame: 40 weeks). 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 30 Aug 2012.