A Trial of Oral BEZ235 and BKM120 in Combination With Paclitaxel With or Without Trastuzumab

Novartis

Status and phase: Completed; Phase 1

Conditions: Metastatic or Locally Advanced Solid Tumors

Treatments: Drug: BEZ235 + paclitaxel + trastuzumab; Drug: BKM120 + paclitaxel; Drug: BEZ235 + paclitaxel; Drug: BKM120 + paclitaxel + trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01285466

CBEZ235A2118

2010-022331-11 (EudraCT Number)

Details and patient eligibility

About

The purpose of the trial is to determine the maximum tolerated dose (MTD) of BEZ235 and BKM120 in combination with weekly paclitaxel and weekly paclitaxel/trastuzumab.

Enrollment: 110 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients with metastatic or locally advanced solid tumors, for whom weekly paclitaxel treatment is indicated (BEZ235-paclitaxel /BKM120-paclitaxel treatment)
• HER2+ metastatic or locally advanced breast cancer patients eligible for weekly paclitaxel and trastuzumab (BEZ235-paclitaxel-trastuzumab /BKM120-paclitaxel-trastuzumab treatment)
• Adult patients (≥ 18 years) (males, females)
• World Health Organization (WHO) performance status ≤ 2
• Adequate bone marrow function:
• Adequate hepatic and renal function:

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 (including radiation and/or surgery) completion, clinically stable with respect to the tumor at the time of study entry, and not receiving enzyme-inducing antiepileptic drugs or corticosteroid therapy or taper, as treatment of the brain metastases
• Patients who have received prior systemic anticancer therapy within the following time frames
• Cyclical chemotherapy: ≤ 3 weeks before study treatment (6 weeks for patients treated with nitrosoureas)
• Biological therapy: ≤ 4 weeks before study treatment, except treatment with trastuzumab (both parts of the trial)
• Investigational drug: ≤ 4 weeks before study treatment
• Patients who have undergone major surgery ≤ 4 weeks before study treatment
• Patients receiving chronic treatment with corticosteroids or other immunosuppressive agents
• Patients with uncontrolled, unmanageable, treatment-refractory diabetes mellitus
• Active or history of major depressive episode, bipolar disorder, obsessive-compulsive disorder, schizophrenia, history of suicide attempt or ideation, or homicide, as judged by the investigator and/or based on recent psychiatric assessment

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 4 patient groups

BEZ235 + paclitaxel

Experimental group

Treatment:

Drug: BEZ235 + paclitaxel

BKM120 + paclitaxel

Experimental group

Treatment:

Drug: BKM120 + paclitaxel

BEZ235 + paclitaxel + trastuzumab

Experimental group

Treatment:

Drug: BEZ235 + paclitaxel + trastuzumab

BKM120 + paclitaxel + trastuzumab

Experimental group

Treatment:

Drug: BKM120 + paclitaxel + trastuzumab