Vorinostat and Doxorubicin in Treating Patients With Metastatic or Locally Advanced Solid Tumors

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase I trial is studying the side effects and best dose of vorinostat when given together with doxorubicin in treating patients with metastatic or locally advanced solid tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may help doxorubicin work better by making tumor cells more sensitive to the drug.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Doxorubicin; Liposomal doxorubicin; Vorinostat

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed solid tumor malignancies for which no curative therapy exists

• Measurable or evaluable disease with tumor that is accessible to biopsy as determined by CT scan or ultrasound

• Skin, lymph nodes, or chest wall lesions are allowed provided measurements are confirmed by 2 independent health care professionals

• No uncontrolled CNS metastases

• Patients with stable CNS metastases (either surgically resected, treated with gamma knife, or stable for 3 months after whole-brain radiotherapy and documented by MRI within the past 4 weeks) are eligible

• Willing to undergo pre- and post-vorinostat tumor biopsies

• Life expectancy ≥ 3 months

• ECOG performance status 0-2

• WBC > 3,000/mm^3

• Absolute neutrophil count > 1,500/mm^3

• Hemoglobin > 9.0 g/dL

• Platelet count > 100,000/mm^3 (transfusion independent)

• Creatinine ≤ 2.0 mg/mL

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST and ALT ≤ 1.5 times ULN

• LVEF > 50%

• Fertile patients must use effective contraception during and for 6 months after completion of study treatment

• Negative pregnancy test

• Not pregnant or nursing

• No significant active infection (e.g., pneumonia, cellulitis, or wound abscess)

• No history of cardiac failure

• No history of long QT syndrome (QTc > 470 msec)

• No history of ventricular tachycardia or fibrillation

• No history of seizures

• No history of allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat or other agents used in the study

• More than 3 weeks since prior chemotherapy or radiotherapy (2 weeks for weekly regimens)

• More than 2 weeks since prior valproic acid or any other histone deacetylase inhibitors

• No prior anthracycline exposure

• No other concurrent chemotherapy

• No concurrent hormonal therapy except for maintenance therapy with luteinizing-hormone releasing-hormone agonists

• No concurrent antiarrhythmics

• No concurrent steroids to control brain metastasis

• No concurrent colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) during the first course of study treatment

• No other concurrent investigational agents for primary disease