Panobinostat and Epirubicin in Treating Patients With Metastatic Malignant Solid Tumors

Plain-language summary

This study evaluates the drugs Panobinostat and Epirubicin in patients with metastatic solid tumors for which no curative therapy exists. It included patients with measurable or evaluable disease. It was a Phase 1 study and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Completed

Sponsor

University of California, San Francisco

Intervention

epirubicin hydrochloride, panobinostat, gene expression analysis, protein expression analysis, western blotting, immunologic technique, laboratory biomarker analysis, pharmacological study

Start date

9/13/2009

Estimated completion

10/10/2016

Countries

United States

Related genes

Locations

• San Francisco, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

DISEASE CHARACTERISTICS:

* Cytologically or histologically confirmed solid tumor malignancy for which no curative therapy exists

  * Metastatic disease
* Measurable or evaluable disease (i.e., elevated CA-125 or elevated PSA for patients with ovarian cancer or prostate cancer, respectively)
* Disease amenable to biopsy AND patient willing to undergo biopsies (for patients enrolled in the dose expansion cohort only)
* No uncontrolled CNS metastasis

  * Stable CNS metastasis allowed provided patient has undergone complete surgical resection, gamma knife radiotherapy (for isolated lesions) or whole-brain radiotherapy AND the metastasis has been stable for ≥ 6 weeks

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* WBC \> 3,000/mm³
* ANC \> 1,500/mm³
* Hemoglobin \> 9.0 g/dL (RBC transfusion allowed)
* Platelet count \> 100,000/mm³
* AST/ALT ≤ 1.5 times upper limit of normal (ULN)
* Serum bilirubin ≤ 1.3 times ULN
* Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min by 24-hour urine collection
* Total serum calcium (corrected for serum albumin) or ionized calcium ≥ lower limit of normal
* Serum potassium ≥ 4.0 mEq/L (supplementation allowed)
* Serum magnesium normal (supplementation allowed)
* Serum sodium ≥ 130 mEq/L
* Serum albumin ≥ 3 g/dL
* Elevated alkaline phosphatase or gamma-glutamyl-transferase due to bone metastasis or liver metastasis allowed
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective double-method (including barrier) contraception during and for 3 months after completion of study treatment
* QTc \< 460 ms
* No evidence of significant active infection (e.g., pneumonia, cellulitis, or wound abscess)
* No impaired cardiac function, including any of the following:

  * Complete left bundle branch block or use of a permanent cardiac pacemaker
  * Congenital long QT syndrome
  * History or presence of ventricular tachyarrhythmias
  * Clinically significant resting bradycardia (\< 50 beats per minute)
  * QTcF \> 470 msec on screening ECG
  * Right bundle branch block plus left anterior hemiblock (bifascicular block)
  * Atrial fibrillation (ventricular heart rate \> 100 beats per minute)
  * Angina pectoris or acute myocardial infarction within the past 6 months
  * New York Heart Association class III-IV congestive heart failure
  * LVEF \< 50% on baseline MUGA or ECHO
* No history of seizures

PRIOR CONCURRENT THERAPY:

* No prior cumulative anthracycline dose \> 300 mg/m² of doxorubicin hydrochloride or \> 480 mg/m² of epirubicin hydrochloride
* More than 5 days since prior valproic acid
* More than 3 weeks since prior and no other concurrent chemotherapy, hormonal therapy, radiotherapy, or experimental anticancer therapy for the primary disease
* No other concurrent HDAC inhibitors
* No concurrent medications that may induce torsades de pointes or cause QTc prolongation
* No other concurrent investigational or anticancer therapy
* No concurrent CYP3A4 inhibitors (including grapefruit or grapefruit juice) and/or CYP3A4 inducers
* No concurrent anti-arrhythmic therapy