Study of PI3 Kinase/mTOR Inhibitor BEZ235 Twice Daily for Advanced Solid Tumors

NCT01343498 | Completed Phase 1

• 1 other identifier: SCRI REFMAL 233
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

This is a dose escalation trial to evaluate twice daily dosing of the sachet formulation of BEZ235. This trial will find the maximum tolerated dose (MTD) of the sachet formulation given twice daily, as well as evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of the twice daily dosing. Patients will initially be given once daily dosing to determine the PK and PD of the single daily dose. On Day 9, they will begin twice daily dosing, with half of the single daily dose divided twice daily, and PK and PD of the twice daily dose will be determined.

Conditions

Malignant Solid Tumour

Keywords

Solid Tumor Malignancy; Advanced Solid Tumors; BEZ235; mTOR Inhibitor

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of BEZ235 given twice daily

  To determine the maximum tolerated dose (MTD) of BEZ235 given twice daily in patients with advanced solid tumors

  18 months

Secondary Outcomes (3)

• To describe the toxicities of this regimen

  18 months

• Clinical Efficacy

  18 months

• PK profile of BEZ235

  18 months

Study Arms (1)

BEZ235

EXPERIMENTAL

Drug: BEZ235

Interventions

BEZ235 DRUG

BEZ235 will be given on a dose-escalation design, beginning at 200 mg BID (SDS sachet) in 3 patients and progressing to 400 mg, 600 mg, and 800 mg respectively based on tolerability.

BEZ235

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of solid tumor malignancy that is metastatic or unresectable and not responsive to standard therapies or for which there is no effective therapy.
• Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1.
• Patient has recovered (to grade ≤ 1) from all clinically significant toxicities related to prior antineoplastic therapies with the exception of alopecia and bone marrow and organ functions (described separately).
• Adequate organ system function, defined as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL
• INR ≤ 2
• Fasting plasma glucose ≤ 140 mg/dL
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x the upper limit of normal (ULN) if no liver involvement or ≤ 5 x the upper limit of normal with liver involvement.
• Creatinine ≤ 1.5 x ULN, OR calculated creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft-Gault method, OR 24-hour measured urine creatinine clearance ≥ 50 mL/min.
• Ability to swallow and retain oral medication.
• Life expectancy of ≥ 3 months.
• Male patients willing to use adequate contraceptive measures.

You may not qualify if:

• Patients currently receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy \[with the exception of LHRH agonists for prostate cancer\], surgery and/or tumor embolization).
• Use of an investigational drug within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of BEZ235. For investigational drugs for which 5 half-lives is less than 21 days, a minimum of 10 days between termination of the investigational drug and administration of BEZ235 is required. In addition, any drug-related toxicity should have recovered to grade 1 or less.
• Any major surgery, radiotherapy, or immunotherapy within the last 28 days (limited palliative radiation is allowed ≥ 2 weeks). Chemotherapy regimens with delayed toxicity within the last 4 weeks (or within the last 6 weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last 2 weeks.
• Patient has received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study drug or has not recovered from side effects of such therapy.
• Leptomeningeal metastases or spinal cord compression due to disease.
• Patients with previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if there is no evidence of central nervous system (CNS) disease progression, and at least 2 weeks have elapsed since treatment. Patients are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs) during the study and should not be receiving chronic corticosteroid therapy for CNS metastases.
• Patients with acute or chronic pancreatitis.
• Patients with diabetes mellitus requiring insulin treatment or a history of gestational diabetes mellitus.
• Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of BEZ235 (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea ≥ grade 2, and malabsorption syndrome).
• Patient has active cardiac disease including any of the following:
• Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
• QTcF \> 480 msec on screening ECG
• Unstable angina pectoris
• Ventricular arrhythmias except for benign premature ventricular contractions
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator

Study Sites (2)

Oklahoma University

Oklahoma City, Oklahoma, 71304, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Interventions

dactolisib

Study Officials

• Johanna C Bendell, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: April 22, 2011
• First Posted: April 28, 2011
• Study Start: April 1, 2011
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: May 1, 2015

Record last verified: 2015-04

Locations

US (2)