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Completed

NCT Number: NCT01482156

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

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Key information

Conditions

Advanced Solid Tumors Adenocarcinoma Breast Diseases Breast Neoplasms Carcinoma Carcinoma, Renal Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Metastatic Breast Cancer Metastatic Renal Cell Carcinoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Skin Diseases Skin and Connective Tissue Diseases Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Wilrijk, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Other names: Afinitor

Primary outcomes

  1. 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

  2. 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

  3. 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.

Secondary outcomes

  1. Time versus blood concentration profiles

    Time frame: First treatment cycle ( 28 days)

    Analysis of pharmacokinetic parameters in blood samples

  2. 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.

  3. 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

  4. 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

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2012
Primary completion
2015
Study completion
2015
First posted
Nov 30, 2011
Registry last updated
Dec 21, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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