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

NCT01482156 | Completed Phase 1

• 2 other identifiers: CRAD001X21092011-001425-24
• Study Type: interventional
• Target: 46
• Locations: 7 countries
• Sites: 10

Brief Summary

Study has two parts:

1. 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. 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

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

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• 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 Outcomes (4)

• Time versus blood concentration profiles

  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

  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

  8 weeks

• Duration of response (DoR) according to local assessments by RECIST 1.0 for RCC and MBC in dose expansion phase

  8 weeks

Study Arms (1)

RAD001 + BEZ235

EXPERIMENTAL

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

Interventions

RAD001 + BEZ235 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.

Also known as: Afinitor

RAD001 + BEZ235

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, 72703, United States

Location

Washington University School of Medicine Washington University (16)

St Louis, Missouri, 63110, United States

Location

Medical University of South Carolina SC

Charleston, South Carolina, 29425, United States

Location

Novartis Investigative Site

Wilrijk, 2610, Belgium

Location

Novartis Investigative Site

Bordeaux, 33075, France

Location

Novartis Investigative Site

Montellier Cedex 5, 34298, France

Location

Novartis Investigative Site

Verona, VR, 37126, Italy

Location

Novartis Investigative Site

Auckland, New Zealand

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

High Heaton, Newcastle Upon Tyne, NE7 7DN, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Renal Cell

Interventions

Everolimus; dactolisib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2011
• First Posted: November 30, 2011
• Study Start: January 1, 2012
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: December 21, 2020

Record last verified: 2015-11

Locations

US (3); IT (1); BE (1); NZ (1); FR (2); ES (1); GB (1)