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

NCT ID: NCT01482156

Last Updated: 2020-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2015-02-28

Brief Summary

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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

Detailed Description

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Conditions

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Advanced Solid Tumors Metastatic Breast Cancer Metastatic Renal Cell Carcinoma

Keywords

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

RAD001 + BEZ235

Intervention Type DRUG

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.

Interventions

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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 Type DRUG

Other Intervention Names

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Afinitor

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, United States

Site Status

Washington University School of Medicine Washington University (16)

St Louis, Missouri, United States

Site Status

Medical University of South Carolina SC

Charleston, South Carolina, United States

Site Status

Novartis Investigative Site

Wilrijk, , Belgium

Site Status

Novartis Investigative Site

Bordeaux, , France

Site Status

Novartis Investigative Site

Montellier Cedex 5, , France

Site Status

Novartis Investigative Site

Verona, VR, Italy

Site Status

Novartis Investigative Site

Auckland, , New Zealand

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

High Heaton, Newcastle Upon Tyne, United Kingdom

Site Status

Countries

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South Korea United States Belgium France Italy New Zealand Spain United Kingdom

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=14406

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

Other Identifiers

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2011-001425-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001X2109

Identifier Type: -

Identifier Source: org_study_id