Dose Finding Study of RAD001 (Everolimus, Afinitor®) in Combination With BEZ235 in Patients With Advanced Solid Tumors

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01482156
• Other study ID #: CRAD001X2109
• Secondary ID: 2011-001425-24
• Status: Completed
• Phase: Phase 1
• Start date: January 2012
• Est. completion date: February 2015

Study information

• Verified date: November 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Breast Neoplasms
• Carcinoma, Renal Cell
• Metastatic Breast Cancer
• Metastatic Renal Cell Carcinoma

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Wilrijk
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Montellier Cedex 5
Italy	Novartis Investigative Site	Verona	VR
New Zealand	Novartis Investigative Site	Auckland
Spain	Novartis Investigative Site	Barcelona	Catalunya
United Kingdom	Novartis Investigative Site	High Heaton	Newcastle Upon Tyne
United States	Medical University of South Carolina SC	Charleston	South Carolina
United States	Highlands Oncology Group Dept of Highlands Oncology Grp	Fayetteville	Arkansas
United States	Washington University School of Medicine Washington University (16)	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  New Zealand,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	First treatment cycle (28 days)
Primary	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	First treatment cycle (28 days)
Primary	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.	12 months
Secondary	Time versus blood concentration profiles	Analysis of pharmacokinetic parameters in blood samples	First treatment cycle ( 28 days)
Secondary	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.	8 weeks
Secondary	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	8 weeks
Secondary	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	8 weeks

External Links

•   Results for CRAD001X2109 can be found on the Novartis Clinical Trial Results Website