The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01482156




Registration number
NCT01482156
Ethics application status
Date submitted
26/09/2011
Date registered
29/11/2011
Date last updated
18/11/2015

Titles & IDs
Public title
Dose Finding Study of RAD001 (Everolimus, Afinitor®) in Combination With BEZ235 in Patients With Advanced Solid Tumors
Scientific 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
Secondary ID [1] 0 0
2011-001425-24
Secondary ID [2] 0 0
CRAD001X2109
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Metastatic Breast Cancer 0 0
Metastatic Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RAD001 + BEZ235

Experimental: RAD001 + BEZ235 - 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.


Treatment: Drugs: RAD001 + BEZ235
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
First treatment cycle (28 days)
Primary outcome [2] 0 0
?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
Timepoint [2] 0 0
First treatment cycle (28 days)
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
12 months
Secondary outcome [1] 0 0
Time versus blood concentration profiles - Analysis of pharmacokinetic parameters in blood samples
Timepoint [1] 0 0
First treatment cycle ( 28 days)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
8 weeks
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
8 weeks
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
8 weeks

Eligibility
Key inclusion criteria
- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
South Carolina
Country [4] 0 0
Belgium
State/province [4] 0 0
Wilrijk
Country [5] 0 0
France
State/province [5] 0 0
Bordeaux Cedex
Country [6] 0 0
France
State/province [6] 0 0
Montellier cedex 5
Country [7] 0 0
Italy
State/province [7] 0 0
VR
Country [8] 0 0
New Zealand
State/province [8] 0 0
Auckland
Country [9] 0 0
Spain
State/province [9] 0 0
Catalunya
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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. 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
Trial website
https://clinicaltrials.gov/show/NCT01482156
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Other publications