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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01482156
First received: September 26, 2011
Last updated: November 18, 2014
Last verified: November 2014
  Purpose

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

Condition Intervention Phase
Advanced Solid Tumors
Metastatic Breast Cancer
Metastatic Renal Cell Carcinoma
Drug: RAD001 + BEZ235
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Probability of a Dose Limiting Toxicity (DLT) by the end of the first treatment cycle (DLT) [ Time Frame: First treatment cycle (28 days) ] [ Designated as safety issue: Yes ]
    The maximum tolerated dose (MTD) and the dose limiting toxicities during the first cycle of treatment

  • 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) ] [ Designated as safety issue: Yes ]
    Frequency of DLTs during the first cycle of treatment

  • Number of participants with adverse events and serious adverse events. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Measured by abnormal safety laboratory parameters, changes in electrocardiograms (ECGs), changes in vital signs and changes in physical examination parameters.


Secondary Outcome Measures:
  • Time versus blood concentration profiles [ Time Frame: First treatment cycle ( 28 days) ] [ Designated as safety issue: No ]
    Analysis of pharmacokinetic parameters in blood samples

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    CT or magnetic resonance imaging (MRI) imaging parameters to determine the PFS according to the RECIST 1.0 criteria

  • Duration of response (DoR) according to local assessments by RECIST 1.0 for RCC and MBC in dose expansion phase [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    CT or MRI imaging parameters to determine the duration of response according to the RECIST 1.0 criteria


Enrollment: 46
Study Start Date: January 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Afinitor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01482156

Locations
United States, Arkansas
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, United States, 72703
United States, Missouri
Washington University School of Medicine Washington University (16)
St. Louis, Missouri, United States, 63110
United States, South Carolina
Medical University of South Carolina SC
Charleston, South Carolina, United States, 29425
Belgium
Novartis Investigative Site
Wilrijk, Belgium, 2610
France
Novartis Investigative Site
Bordeaux Cedex, France, 33075
Novartis Investigative Site
Montellier cedex 5, France, 34298
Italy
Novartis Investigative Site
Verona, VR, Italy, 37126
New Zealand
Novartis Investigative Site
Auckland, New Zealand
Spain
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
United Kingdom
Novartis Investigative Site
High Heaton, Newcastle Upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01482156     History of Changes
Other Study ID Numbers: CRAD001X2109, 2011-001425-24
Study First Received: September 26, 2011
Last Updated: November 18, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Ministry of Social Affairs, Public Health and the Environment
France: Ministry of Health
New Zealand: Medsafe
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: Ministry of Health

Keywords provided by Novartis:
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

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma, Renal Cell
Neoplasms
Adenocarcinoma
Breast Diseases
Kidney Diseases
Kidney Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Skin Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014