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

NCT01285466 | Completed Phase 1

• 2 other identifiers: CBEZ235A21182010-022331-11
• Study Type: interventional
• Target: 110
• Locations: 5 countries
• Sites: 10

Brief Summary

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.

Conditions

Metastatic or Locally Advanced Solid Tumors

Keywords

Cancer; BEZ235; BKM120; paclitaxel; trastuzumab

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose limiting toxicities during the first cycle of treatment.

  First treatment cycle (4 weeks)

Secondary Outcomes (4)

• Incidence of safety events during the whole treatment period (until progression of disease).

  From start of treatment until disease progression

• pharmacokinetics of BEZ235, BKM120 and paclitaxel given in combination, on Day 1, 8 and 22.

  First treatment cycle (4 weeks)

• Treatment efficacy (response to treatment according to RECIST criteria)

  From start of treatment until disease progression

• Impact of treatment on biomarkers of Pi3 Kinase pathway (analyses of skin biopsies, circulating markers)

  From start of treatment until disease progression

Study Arms (4)

BEZ235 + paclitaxel

EXPERIMENTAL

Drug: BEZ235 + paclitaxel

BKM120 + paclitaxel

EXPERIMENTAL

Drug: BKM120 + paclitaxel

BEZ235 + paclitaxel + trastuzumab

EXPERIMENTAL

Drug: BEZ235 + paclitaxel + trastuzumab

BKM120 + paclitaxel + trastuzumab

EXPERIMENTAL

Drug: BKM120 + paclitaxel + trastuzumab

Interventions

BEZ235 + paclitaxel DRUG

BEZ235 + paclitaxel

BKM120 + paclitaxel DRUG

BKM120 + paclitaxel

BEZ235 + paclitaxel + trastuzumab DRUG

BEZ235 + paclitaxel + trastuzumab

BKM120 + paclitaxel + trastuzumab DRUG

BKM120 + paclitaxel + trastuzumab

Eligibility Criteria

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

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Wilrijk, 2610, Belgium

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Chur, 7000, Switzerland

Location

Novartis Investigative Site

Sankt Gallen, 9007, Switzerland

Location

Related Links

• Results for CBEZ235A2118 can be found on the Novartis Clinical Trials website

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

dactolisib; Paclitaxel; NVP-BKM120; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2011
• First Posted: January 28, 2011
• Study Start: January 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: December 9, 2020

Record last verified: 2017-02

Locations

BE (3); NL (1); ES (2); CH (2); DE (2)