Panobinostat and Epirubicin in Treating Patients With Metastatic Malignant Solid Tumors

NCT00878904 | Completed Phase 1 DMC

• 3 other identifiers: CDR0000639080UCSF-09991NOVARTIS-CLBH589C
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as epirubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panobinostat together with epirubicin may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with epirubicin in treating patients with metastatic malignant solid tumors.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (3)

• Response as assessed by RECIST criteria

  30 post end of study drug estimated to be ~24 weeks

• Progression as assessed by RECIST criteria

  30 post end of study drug estimated to be ~24 weeks

• Adverse events and other symptoms as assessed by NCI CTCAE v3.0

  30 post end of study drug estimated to be ~24 weeks

Study Arms (1)

treatment with Panobinostat and Epirubicin

EXPERIMENTAL

Drug: epirubicin hydrochloride; Drug: panobinostat; Genetic: gene expression analysis; Genetic: protein expression analysis; Genetic: western blotting; Other: immunologic technique; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

epirubicin hydrochloride DRUG

treatment with Panobinostat and Epirubicin

panobinostat DRUG

treatment with Panobinostat and Epirubicin

gene expression analysis GENETIC

treatment with Panobinostat and Epirubicin

protein expression analysis GENETIC

treatment with Panobinostat and Epirubicin

western blotting GENETIC

treatment with Panobinostat and Epirubicin

immunologic technique OTHER

treatment with Panobinostat and Epirubicin

laboratory biomarker analysis OTHER

treatment with Panobinostat and Epirubicin

pharmacological study OTHER

treatment with Panobinostat and Epirubicin

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143-1711, United States

Location

Related Publications (1)

• Thomas S, Aggarwal R, Jahan T, Ryan C, Troung T, Cripps AM, Raha P, Thurn KT, Chen S, Grabowsky JA, Park J, Hwang J, Daud A, Munster PN. A phase I trial of panobinostat and epirubicin in solid tumors with a dose expansion in patients with sarcoma. Ann Oncol. 2016 May;27(5):947-52. doi: 10.1093/annonc/mdw044. Epub 2016 Feb 21.

  PMID: 26903311 DERIVED

MeSH Terms

Interventions

Epirubicin; Panobinostat; Gene Expression Profiling; Blotting, Western; Immunologic Techniques

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Genetic Techniques; Investigative Techniques; Electrophoresis; Chemistry Techniques, Analytical; Electrochemical Techniques; Immunoblotting; Immunoassay; Molecular Probe Techniques

Study Officials

• Pamela N. Munster, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2009
• First Posted: April 9, 2009
• Study Start: September 13, 2009
• Primary Completion: May 1, 2013
• Study Completion: October 10, 2016
• Last Updated: March 24, 2017

Record last verified: 2017-03

Locations

US (1)