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

December 17, 2020 updated by: Novartis Pharmaceuticals

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:

  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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Wilrijk, Belgium, 2610
        • Novartis Investigative Site
  • France
      • Bordeaux Cedex, France, 33075
        • Novartis Investigative Site
      • Montellier Cedex 5, France, 34298
        • Novartis Investigative Site
  • Italy
    • VR
      • Verona, VR, Italy, 37126
        • Novartis Investigative Site
  • New Zealand
      • Auckland, New Zealand
        • Novartis Investigative Site
  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
  • United Kingdom
    • Newcastle Upon Tyne
      • High Heaton, Newcastle Upon Tyne, United Kingdom, NE7 7DN
        • Novartis Investigative Site
  • United States
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group Dept of Highlands Oncology Grp
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine Washington University (16)
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina SC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
Other Names:
  • Afinitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
Time Frame: First treatment cycle (28 days)
Frequency of DLTs during the first cycle of treatment
First treatment cycle (28 days)
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time versus blood concentration profiles
Time Frame: First treatment cycle ( 28 days)
Analysis of pharmacokinetic parameters in blood samples
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
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
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
CT or magnetic resonance imaging (MRI) imaging parameters to determine the PFS according to the RECIST 1.0 criteria
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
CT or MRI imaging parameters to determine the duration of response according to the RECIST 1.0 criteria
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (ACTUAL)

February 1, 2015

Study Completion (ACTUAL)

February 1, 2015

Study Registration Dates

First Submitted

September 26, 2011

First Submitted That Met QC Criteria

November 29, 2011

First Posted (ESTIMATE)

November 30, 2011

Study Record Updates

Last Update Posted (ACTUAL)

December 21, 2020

Last Update Submitted That Met QC Criteria

December 17, 2020

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRAD001X2109
  • 2011-001425-24 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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