Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Panobinostat

Histone Deacetylase Inhibitors

Antineoplastic Agents, Immunological

Enzyme Inhibitors

Panobinostat intravenously (i.v.) or orally was given in combination with trastuzumab.

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.

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

Novartis Pharmaceuticals

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.

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

A Phase Ib/IIa Trial of Panobinostat in Combination With Trastuzumab in Adult Female Patients With HER2 Positive Metastatic Breast Cancer Whose Disease Has Progressed During or Following Therapy With Trastuzumab

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.

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.

10 mg/m\^2 i.v. was given on day 1 and day 8 of a 21 day cycle.

Escalation: i.v. Arm - 10mg/m^2

15 mg/m\^2 i.v. was given on day 1 and day 8 of a 21 day cycle.

Escalation: i.v. Arm - 15mg/m^2

20 mg/m\^2 i.v. was given on day 1 and day 8 of a 21 day cycle.

Escalation/Expansion: i.v. Arm -20mg/m^2

20 mg was given twice weekly for two consecutive weeks as part of a 21-day treatment cycle.

Oral Arm - Schedule A 20mg

15 mg was given three times weekly for two consecutive weeks as part of a 21-day treatment cycle.

Oral Arm - Schedule B 15 mg

20 mg was given three times weekly for two consecutive weeks as part of a 21-day treatment cycle.

Oral Arm - Schedule B 20mg

Oral Arm - Schedule B 15mg

Total

Age, Continuous

Female

Sex/Gender, Customized

Study Director

Expansion: i.v. Arm -20mg/m^2

The Maximum Tolerated Dose (MTD) determining set was used for this analysis. The MTD determining set consisted of all participants who either received sufficient study drug and had sufficient safety evaluations or discontinued due to unacceptable toxicity.

Number of Participants With Dose Limiting Toxicities (DLTs)

Complete response

Partial response

Stable disease

Progressive disease

Unknown

The full analysis set was analyzed. The full analysis set included all randomized participants.

Spots Global Cancer Trial Database for 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

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