A phase Ib multi-center, open-label, 4-arm dose-escalation study of oral BEZ235 and BKM120 in combination with weekly paclitaxel in patients with advanced solid tumors and weekly paclitaxel/trastuzumab in patients with HER2+ metastatic breast cancer.

A phase Ib multi-center, open-label, 4-arm dose-escalation study of oral BEZ235 and BKM120 in combination with weekly paclitaxel in patients with advanced solid tumors and weekly paclitaxel/trastuzumab in patients with HER2+ metastatic breast cancer. - BEZ235 or BKM120 with paclitaxel or paclitaxel/trastuzumab (phase IB)

Status

Recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON34229

Enrollment

Registered

2010-12-29

Start date

2011-07-07

Completion date

Unknown

Last updated

2024-05-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

advanced solid tumors HER2-positive Breast Cancer

Interventions

• BEZ235: starting dose 400 mg/day • BKM120: starting dose 40 mg/day • Paclitaxel: 70 mg/m2 • Trastuzumab: 2 mg/kg (if applicable starting dose of 4mg/kg) Arm 1: Paclitaxel + BEZ235 Arm 2: Paclitaxe

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: Dual-agent part: • Patients with metastatic or locally advanced solid tumors eligible for weekly paclitaxel;Triple-agent part: • HER2+ metastatic or locally advanced breast cancer patients eligible for weekly paclitaxel and trastuzumab;For both parts: • WHO performance status = 1.5 ×109/L • Hemoglobin >= 10g/dL = 6.2 mmol/L • Platelets >= 100 ×109/L • Serum albumin >= 3.0 g/dL • AST/SGOT and ALT/SGPT = 50 mL/min • Partial thromboplastin time (PTT) = 50% (MUGA scan or echocardiogram) • QTc interval

Exclusion criteria

Exclusion criteria: • Patients with primary central nervous system (CNS) tumor or CNS tumor involvement. However, patients with a metastatic CNS lesion may participate in this trial, if the patient is > 4 weeks from therapy completion, clinically stable and not receiving enzyme-inducing antiepileptic drugs or corticosteroid therapy • Patients who have received prior systemic anticancer therapy within the following time frames - Chemotherapy

Design outcomes

Primary

Measure	Time frame
Incidence of dose-limiting toxicities (DLTs) in patients with concomitant administration of BEZ235 or BKM120 and paclitaxel (± trastuzumab).	—

Secondary

Measure	Time frame
• Safety and tolerability: type, frequency, and severity of adverse events (AEs), adverse drug reactions, and laboratory abnormalities per CTCAEv4.0 (Common Toxicity Criteria for Adverse Events, version 4.0) • Pharmacokinetics: • Time versus plasma concentration profiles of paclitaxel as single agent and in combination treatment • Time versus plasma concentration profiles of BEZ235 and BKM120 in combination treatment • Trastuzumab trough levels • Basic PK parameters for paclitaxel, BEZ235, and BKM120 including, but not limited to, AUCtlast, AUCinf, AUC0-24, Cmax, tmax, terminal t1/2, and other PK parameters if deemed appropriate • Overall response per RECIST Exploratory endpoints : • Antitumor activity: standard circulating tumor markers • Phospho-S6 ribosomal protein (p-S6) in skin • Increase in tumor apoptotic markers (circulating markers) • PI3K pathway analysis (PIK3CA mutation, PTEN alteration in tumors) • New biomarkers will be integrated if developed during this trial and considered appropriate for judgment of efficacy and safety • Basic PK parameters for the paclitaxel metabolites including, but not limited to, AUC0-tlast, AUC0-inf, AUC0-24, Cmax, tmax, terminal t1/2, and other PK parameters if deemed appropriate	—

Measure

Time frame

• Safety and tolerability: type, frequency, and severity of adverse events (AEs), adverse drug reactions, and laboratory abnormalities per CTCAEv4.0 (Common Toxicity Criteria for Adverse Events, version 4.0) • Pharmacokinetics: • Time versus plasma concentration profiles of paclitaxel as single agent and in combination treatment • Time versus plasma concentration profiles of BEZ235 and BKM120 in combination treatment • Trastuzumab trough levels • Basic PK parameters for paclitaxel, BEZ235, and BKM120 including, but not limited to, AUCtlast, AUCinf, AUC0-24, Cmax, tmax, terminal t1/2, and other PK parameters if deemed appropriate • Overall response per RECIST Exploratory endpoints : • Antitumor activity: standard circulating tumor markers • Phospho-S6 ribosomal protein (p-S6) in skin • Increase in tumor apoptotic markers (circulating markers) • PI3K pathway analysis (PIK3CA mutation, PTEN alteration in tumors) • New biomarkers will be integrated if developed during this trial and considered appropriate for judgment of efficacy and safety • Basic PK parameters for the paclitaxel metabolites including, but not limited to, AUC0-tlast, AUC0-inf, AUC0-24, Cmax, tmax, terminal t1/2, and other PK parameters if deemed appropriate

—

Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)