Clinical trial NCT01482156: Dose Finding Study of RAD001 (Everolimus, Afinitor®) in Combination With BEZ235 in Patients With Advanced Solid Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Metastatic Breast Cancer
Metastatic Renal Cell Carcinoma
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-11-30
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Probability of a Dose Limiting Toxicity (DLT) by the end of the first treatment cycle (DLT)
timeFrame: First treatment cycle (28 days)
measure: Incidence of DLT in patients by the end of the first treatment cycle in the co-administration of RAD001 and BEZ235
timeFrame: First treatment cycle (28 days)
measure: Number of participants with adverse events and serious adverse events.
timeFrame: 12 months
Secondary outcomes:
measure: Time versus blood concentration profiles
timeFrame: First treatment cycle ( 28 days)
measure: 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
timeFrame: 8 weeks
measure: 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
timeFrame: 8 weeks
measure: Duration of response (DoR) according to local assessments by RECIST 1.0 for RCC and MBC in dose expansion phase
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group Dept of Highlands Oncology Grp
state: Arkansas
city: Saint Louis
country: United States
facility: Washington University School of Medicine Washington University (16)
state: Missouri
city: Charleston
country: United States
facility: Medical University of South Carolina SC
state: South Carolina
city: Wilrijk
country: Belgium
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Montellier Cedex 5
country: France
facility: Novartis Investigative Site
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Auckland
country: New Zealand
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: High Heaton
country: United Kingdom
facility: Novartis Investigative Site
state: Newcastle Upon Tyne
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: