A Trial of Panobinostat and Trastuzumab for Adult Female Patients With HER2 Positive Metastatic Breast Cancer (MBC) Whose Disease Has Progressed on or After Trastuzumab

Phase 2TerminatedNCT00567879

Novartis Pharmaceuticals56 enrolled

Overview

The primary purpose of this study is to identify the maximum tolerated dose (MTD) of both intravenous and oral panobinostat plus trastuzumab. The study will evaluate safety and efficacy of the combination in adult female patients with HER2+ metastatic breast cancer

This phase Ib/IIa study was prematurely terminated due to lack of efficacy noted in 55 patients with HER2-positive MBC who had progressed on or following a trastuzumab-based therapy.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Cancer

Interventions

PanobinostatDRUG

Participants received escalating doses of panobinostat until the maximum tolerated dose (MTD) was reached. The starting dose of panobinostat i.v. was 10mg/m\^2 at days 1 and 8 during a 21-day treatment cycle. The oral panobinostat starting dose was 20 mg twice weekly.

TrastuzumabDRUG

Fixed doses of trastuzumab were given in parallel with panobinostat. Trastuzumab i.v. was given weekly according to the instruction in the package insert.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion criteria: * Age \> 18 year old * Confirmed HER2+ ve metastatic breast cancer * Prior treatment and progression on trastuzumab * Patients must have adequate laboratory values * Eastern Cooperative Oncology Group (ECOG) performance status of \<2 Key Exclusion criteria: * Patients with active central nervous system (CNS) disease or brain metastases except those who have been previously treated and have been stable for at least 3 months. * Impaired heart function or clinically significant heart disease * Impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of LBH589 * Ongoing diarrhea * Liver or renal disease with impaired hepatic or renal functions * Concomitant use of any anti-cancer therapy or certain drugs * Female patients who are pregnant or breast feeding * Patients not willing to use an effective method of birth control

Locations (20)

University of California at Los Angeles

Los Angeles, California, United States

University of Colorado Dept. of Univ. of Colorado

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicities (DLTs)

Safety data was reviewed to determine the DLTs. DLTs comprised adverse events (AEs) or abnormal laboratory values that occurred at any time and were assessed as clinically relevant and meeting any of the following criteria: considered to be related to the study treatment and unrelated to disease, disease progression, inter-current illness, or concomitant medications. Toxicities were assessed using the National Cancer Institute common terminology criteria for adverse events (NCI CTCAE), version 3.0. Disease related symptoms were not considered a DLT.

Time frame: day 21

Secondary Outcomes

Number of Participants With Best Overall Response

Tumors were assessed according to Response Evaluation Criteria in Solid tumors (RECIST). Complete response (CR): disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR): \> 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD): neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; Progressive disease (PD): \> 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm.

Time frame: day 21

Data from ClinicalTrials.gov

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