Status:

COMPLETED

Phase I Trial of Valproic Acid and Epirubicin in Solid Tumor Malignancies

Lead Sponsor:

H. Lee Moffitt Cancer Center and Research Institute

Collaborating Sponsors:

National Cancer Institute (NCI)

Pfizer

Conditions:

Neoplasms, Advanced

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

This is a Phase I dose escalation trial with escalating doses of Valproic acid and one dose escalation step of epirubicin. VPA will be escalated starting at a dose that is recommended for use as an an...

Detailed Description

This is a Phase I dose escalation trial with escalating doses of Valproic acid and one dose escalation step of epirubicin. VPA will be escalated starting at a dose that is recommended for use as an an...

Eligibility Criteria

Inclusion

  • Patients must have cytologically/histologically documented solid tumor malignancies
  • Age \> 18 years old
  • Patients must have ECOG performance status 0-2
  • Patients must be able to give informed consent and able to follow guidelines given in the study
  • The patient has no major impairment of hematological function, as defined by the following laboratory parameters: WBC \>3.0x109/L; ANC \> 1.5 x 109/L; Hgb \>9.0g/dL; PLT \>100x109/L (untransfused). Red blood cell transfusions and repeat evaluations for study entry are allowed
  • All patients of reproductive potential must use an effective method of contraception during the study and six months following termination of treatment. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to female patients who are older than 50 years and have not had a menstrual cycle in more than one year.
  • Patients must have measurable or evaluable disease by staging studies performed within 4 weeks of enrollment (evaluable disease refers to ovarian cancer with an elevated CA-125 or prostate cancer with elevated PSA only)
  • Once MTD for VPA and epirubicin is reached, the trial will be limited to patients with breast cancer
  • At the MTD for VPA and FEC MTD for the trial will be expanded to 15 patients with advanced (inflammatory, Stage \>IIIB or regional stage IV) or metastatic breast cancer.
  • Patients must have biopsiable disease and be willing to undergo pre and post-VPA biopsies in cycle 1; Patients must have measurable disease, Patients from the last cohort may be included if they were biopsied

Exclusion

  • Patients may not have had cumulative anthracycline exposure greater than doxorubicin 300 mg/m2 or epirubicin 600 mg/m2.
  • Patients must not have evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study entry.
  • Patients must have adequate renal and normal hepatic function (creatinine \< 1.5 x upper limit of normal (ULN), bilirubin and SGOT (AST), SGPT (ALT) within 1.5 x the upper institutional normal limits) obtained within 4 weeks prior to registration.
  • Pregnant and breast feeding women are excluded from the study because effects on the fetus are unknown and there may be a risk of increased fetal wastage.
  • Women of childbearing age must have a negative pregnancy test and be willing to use a highly effective method of contraception. Men who are sexually active must also be willing to use an accepted and effective method of contraception.
  • Patients taking anti-arrhythmic medication or with a history of cardiac failure or with ejection fraction £ 50 % are excluded. Patients with a history of long QT syndrome are excluded from study. Patients with a history of ventricular tachycardia or fibrillation are also excluded. Patients must have normal sinus rhythm and normal PR and QT intervals on EKG.
  • Patients with uncontrolled CNS metastasis or a history of seizures are excluded. Patients with stable CNS metastasis (either surgically resected, treated with gamma knife or stable for 3 months following WBRT are eligible)
  • Patients with stable brain metastases will need an MRI within 4 weeks prior to start of therapy

Key Trial Info

Start Date :

March 1 2004

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

April 1 2008

Estimated Enrollment :

82 Patients enrolled

Trial Details

Trial ID

NCT00246103

Start Date

March 1 2004

End Date

April 1 2008

Last Update

February 23 2017

Active Locations (1)

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1

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States, 33612