Advanced Solid TumorsPhase 1NCT01482156
Dose Finding Study of RAD001 (Everolimus, Afinitor®) in Combination With BEZ235 in Patients With Advanced Solid Tumors
A Phase 1 study testing RAD001 + BEZ235 in people with Advanced Solid Tumors and Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 10 sites in 7 countries.
Trial summary
Study has two parts: 1. Dose-finding: to determine the maximum tolerated dose (MTD) and to evaluate the safety and tolerability of RAD001 (everolimus , Afinitor®) in combination with BEZ235 in patients with advanced solid tumors. 2. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Metastatic Breast Cancer, Metastatic Renal Cell Carcinoma
- What is being tested?
- RAD001 + BEZ235
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 10 sitesin 7 countries
- Study dates
- Jan 2012to Feb 2015
- Phase
- Phase 1
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients age 18 years or older
- In the dose finding phase, patients with histologically or cytologically confirmed advanced solid malignancies that are metastatic or unresectable
- In the dose expansion phase, the enrollment will be limited to patients with:
- Patients with metastatic renal cell carcinoma (mRCC) whose disease had progressed despite prior treatment with VEGFR-TKI (vascular endothelial growth factor receptor tyrosine kinase inhibitor) therapy (at least one but no more than two lines of VEGFR-TKI therapy) Patients with metastatic breast cancer (MBC) which is ER+/HER2-, whose disease had progressed despite prior treatment with at least one but no more than two lines of chemotherapy and at least one prior line of endocrine therapy in the metastatic setting
- WHO performance status of 0-2
- Lab parameters within specifically defined criteria
- Patients with measurable disease per RECIST 1.0
Who cannot join
- Patients who have previously received mTOR inhibitors or PI3K inhibitors
- Patients with CNS metastases unless previously treated with surgery, whole-brain radiation or stereotactic radiosurgery plus the disease having been stable for at least 2 months without steroid use for at least 1 month prior to the first dose of RAD001 and BEZ235. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs.
- Major surgery within 2 weeks prior to study enrollment
- Patient taking anti-cancer drug concomitantly
- Received radiation within 4 weeks prior to study enrollment (2 weeks if limited field radiation)
- Receive chemotherapy 4 weeks prior to study enrollment
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- Received live attenuated vaccines within 1 week prior to study enrollment
- History of HIV
- Any other severe and/or uncontrolled medical condition
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
10 sites in 7 countries.
10 sites in 7 countries
United States3 sites
Medical University of South Carolina SC
Charleston, South Carolina, 29425
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, 72703
Washington University School of Medicine Washington University (16)
St Louis, Missouri, 63110
France2 sites
Novartis Investigative Site
Bordeaux, 33075
Novartis Investigative Site
Montellier Cedex 5, 34298
United Kingdom1 site
Novartis Investigative Site
High Heaton, Newcastle Upon Tyne, NE7 7DN
About this study
Official title: An Open-label, Multi-center Phase I Dose-finding Study of RAD001 (Everolimus, Afinitor®) in Combination With BEZ235 in Patients With Advanced Solid Tumors
Study has two parts:
- Dose-finding: to determine the maximum tolerated dose (MTD) and to evaluate the safety and tolerability of RAD001 (everolimus , Afinitor®) in combination with BEZ235 in patients with advanced solid tumors.
- Dose-expansion: to assess safety and tolerability of RAD001 and BEZ235 at the MTD in patients with ER+/HER2- metastatic breast cancer and metastatic renal cell cancer
- Being tested
- RAD001 + BEZ235
- Keywords
- Advanced solid tumors, Metastatic renal cell carcinoma (mRCC), ER+/HER2-Metastatic breast cancer (MBC), Dose finding study, mTOR, Pl3K, BEZ235, RAD001, Everolimus, Afinitor®, ER+/HER2- metastatic breast cancer
- Medical subject headings
- Breast Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001 + BEZ235Drug
Also called Afinitor
RAD001 is formulated as tablets of 2.5 mg and 5 mg strength, blistered in units of 10 tablets (for oral use) each. Blisters should be opened only at the time of dministration as the drug is both hygroscopic and light-sensitive. RAD001 should be administered immediately after a meal with a large glass of water. BEZ235 is supplied as 50-mg, 200-mg, 300-mg and 400-mg sachets (for oral use). BEZ235 is packaged in aluminum foil bags. Bags are packaged in a box. Patients will receive RAD001 in combination with BEZ235.
| Study group | Role | What they receive |
|---|---|---|
| RAD001 + BEZ235 | Experimental | Patients will receive first dose of RAD001 at 2.5mg/5mg/10 mg weekly or 2.5mg/5mg daily in combination of BEZ235 at 50 mg/100 mg/200 mg/300 mg/400 mg twice a day. In the initial cohort of the dose finding phase, patients will receive a single 2.5 mg dose of RAD001 on Cycle 1 Day 1 and the combination therapy of RAD001 2.5 mg/week and BEZ235 200 mg bid starting on Cycle 1 Day 8. Dose escalation phase: patients will start RAD001 and BEZ235 on Cycle 1 Day 1 with both study drugs being administered at the center. Dose expansion phase: the first 15 patients enrolled at selected sites will take RAD001 as monotherapy from Day 1 to Day 7 (for PK sampling). The combination therapy of RAD001 and BEZ235 will start on Day 8. All remaining patients will receive the combination therapy of RAD001 and BEZ235 starting on Cycle 1 Day 1. Receives: Drug: RAD001 + BEZ235 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Probability of a Dose Limiting Toxicity (DLT) by the end of the first treatment cycle (DLT)
The maximum tolerated dose (MTD) and the dose limiting toxicities during the first cycle of treatment
Measured: First treatment cycle (28 days)
Incidence of DLT in patients by the end of the first treatment cycle in the co-administration of RAD001 and BEZ235
Frequency of DLTs during the first cycle of treatment
Measured: First treatment cycle (28 days)
Number of participants with adverse events and serious adverse events.
Measured by abnormal safety laboratory parameters, changes in electrocardiograms (ECGs), changes in vital signs and changes in physical examination parameters.
Measured: 12 months
Secondary outcomes (4)
Time versus blood concentration profiles
Analysis of pharmacokinetic parameters in blood samples
Measured: First treatment cycle ( 28 days)
Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR)) according to local assessments by RECIST 1.0 for renal cell carcinoma (RCC) and metastatic breast cancer (MBC) in dose expansion phase
CT or MRI imaging parameters to determine the overall response rate (complete response, partial response, stable disease, or progressive disease) according to the RECIST 1.0 criteria.
Measured: 8 weeks
Progresive Free Survival (PFS) according to local assessments by RECIST 1.0 for renal cell carcinoma (RCC) and metastatic breast cancer (MBC) in dose expansion phase
CT or magnetic resonance imaging (MRI) imaging parameters to determine the PFS according to the RECIST 1.0 criteria
Measured: 8 weeks
Duration of response (DoR) according to local assessments by RECIST 1.0 for RCC and MBC in dose expansion phase
CT or MRI imaging parameters to determine the duration of response according to the RECIST 1.0 criteria
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2011 (estimated)
- Study startJan 2012
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 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
- NCT01482156
- Sponsor's protocol ID
- CRAD001X2109
- Other IDs
- 2011-001425-24
- Status last verified
- Nov 2015
- First submitted
- 26 Sep 2011
- Last updated
- 21 Dec 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center Phase I Dose-finding Study of RAD001 (Everolimus, Afinitor®) in Combination With BEZ235 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01482156
- Acronym / sponsor ID
- CRAD001X2109
- Keywords
- Advanced solid tumors, Metastatic renal cell carcinoma (mRCC), ER+/HER2-Metastatic breast cancer (MBC), Dose finding study, mTOR, Pl3K, BEZ235, RAD001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 30 Nov 2011 (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.
Study has two parts:
- Dose-finding: to determine the maximum tolerated dose (MTD) and to evaluate the safety and tolerability of RAD001 (everolimus , Afinitor®) in combination with BEZ235 in patients with advanced solid tumors.
- Dose-expansion: to assess safety and tolerability of RAD001 and BEZ235 at the MTD in patients with ER+/HER2- metastatic breast cancer and metastatic renal cell cancer
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 + BEZ235 | Experimental | Drug: RAD001 + BEZ235Patients will receive first dose of RAD001 at 2.5mg/5mg/10 mg weekly or 2.5mg/5mg daily in combination of BEZ235 at 50 mg/100 mg/200 mg/300 mg/400 mg twice a day. In the initial cohort of the dose finding phase, patients will receive a single 2.5 mg dose of RAD001 on Cycle 1 Day 1 and the combination therapy of RAD001 2.5 mg/week and BEZ235 200 mg bid starting on Cycle 1 Day 8. Dose escalation phase: patients will start RAD001 and BEZ235 on Cycle 1 Day 1 with both study drugs being administered at the center. Dose expansion phase: the first 15 patients enrolled at selected sites will take RAD001 as monotherapy from Day 1 to Day 7 (for PK sampling). The combination therapy of RAD001 and BEZ235 will start on Day 8. All remaining patients will receive the combination therapy of RAD001 and BEZ235 starting on Cycle 1 Day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male and female patients age 18 years or older
- In the dose finding phase, patients with histologically or cytologically confirmed advanced solid malignancies that are metastatic or unresectable
- In the dose expansion phase, the enrollment will be limited to patients with:
- Patients with metastatic renal cell carcinoma (mRCC) whose disease had progressed despite prior treatment with VEGFR-TKI (vascular endothelial growth factor receptor tyrosine kinase inhibitor) therapy (at least one but no more than two lines of VEGFR-TKI therapy) Patients with metastatic breast cancer (MBC) which is ER+/HER2-, whose disease had progressed despite prior treatment with at least one but no more than two lines of chemotherapy and at least one prior line of endocrine therapy in the metastatic setting
- WHO performance status of 0-2
Key exclusion criteria (10 listed)
- Patients who have previously received mTOR inhibitors or PI3K inhibitors
- Patients with CNS metastases unless previously treated with surgery, whole-brain radiation or stereotactic radiosurgery plus the disease having been stable for at least 2 months without steroid use for at least 1 month prior to the first dose of RAD001 and BEZ235. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs.
- Major surgery within 2 weeks prior to study enrollment
- Patient taking anti-cancer drug concomitantly
- Received radiation within 4 weeks prior to study enrollment (2 weeks if limited field radiation)
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 |
|---|---|---|
| RAD001 + BEZ235Also: AfinitorRAD001 is formulated as tablets of 2.5 mg and 5 mg strength, blistered in units of 10 tablets (for oral use) each. Blisters should be opened only at the time of dministration as the drug is both hygroscopic and light-sensitive. RAD001 should be administered immediately after a meal with a large glass of water. BEZ235 is supplied as 50-mg, 200-mg, 300-mg and 400-mg sachets (for oral use). BEZ235 is packaged in aluminum foil bags. Bags are packaged in a box. Patients will receive RAD001 in combination with BEZ235. | Drug | RAD001 + BEZ235 |
Primary outcome
Probability of a Dose Limiting Toxicity (DLT) by the end of the first treatment cycle (DLT)
Time frame: First treatment cycle (28 days)
The maximum tolerated dose (MTD) and the dose limiting toxicities during the first cycle of treatment
Incidence of DLT in patients by the end of the first treatment cycle in the co-administration of RAD001 and BEZ235
Time frame: First treatment cycle (28 days)
Frequency of DLTs during the first cycle of treatment
Number of participants with adverse events and serious adverse events.
Time frame: 12 months
Measured by abnormal safety laboratory parameters, changes in electrocardiograms (ECGs), changes in vital signs and changes in physical examination parameters.
4 secondary outcomes
Time versus blood concentration profiles
Time frame: First treatment cycle ( 28 days)
Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR)) according to local assessments by RECIST 1.0 for renal cell carcinoma (RCC) and metastatic breast cancer (MBC) in dose expansion phase
Time frame: 8 weeks
Progresive Free Survival (PFS) according to local assessments by RECIST 1.0 for renal cell carcinoma (RCC) and metastatic breast cancer (MBC) in dose expansion phase
Time frame: 8 weeks
Duration of response (DoR) according to local assessments by RECIST 1.0 for RCC and MBC in dose expansion phase
Time frame: 8 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 21 Dec 2020.
- Results for CRAD001X2109 can be found on the Novartis Clinical Trial Results WebsiteLink 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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
10 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RAD001 + BEZ235 in people with Advanced Solid Tumors and Metastatic Breast Cancer, run by Novartis Pharmaceuticals at 10 sites in 7 countries.
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 7 inclusion and 10 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 21 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, France, Belgium, Italy, New Zealand and 2 more countries. 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 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.
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?
Probability of a Dose Limiting Toxicity (DLT) by the end of the first treatment cycle (DLT) (time frame: First treatment cycle (28 days)). The study lists 3 primary outcomes in all. 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 21 Dec 2020.