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

NCT00246103 | Completed Phase 1

• 2 other identifiers: MCC-13693USFIRB#101881
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

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 anti-convulsant or to treat migraine headaches. Epirubicin will be given by infusion on day 3 after the last dose of divalproex. The study will determine the highest dose that these two drugs can be given together and as part of a multidrug regimen with 5-fluorouracil and cyclophosphamide.

Conditions

Neoplasms, Advanced

Keywords

Valproic Acid; Epirubicin; Solid Tumor; Malignancies

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  MTD of Valproic acid in combination with Epirubicin. The maximum tolerated dose (MTD) will be defined as the highest dose level at which less than 2 out of 6 patients (\<33%) experience DLT in Cycle 1. A dose limiting toxicity (DLT) will be defined as any one of the specific adverse events (AEs) outlined in the protocol, occurring during Cycle 1 when considered related to therapy that is part of this study.

  Up to 2 months

Other Outcomes (4)

• Pharmacokinetic Profile

  6 months

• VPA effects on Histone Acetylation

  6 months

• MTD for VPA and Epirubicin in Combination with 5-fluorouracil and Cyclophosphamide

  6 months

Study Arms (1)

Dose Escalation and Possible Expansion

EXPERIMENTAL

Escalating doses of Valproic acid and one dose escalation step of epirubicin. Participants with breast cancer treated at the maximum tolerated dose, will also be treated with 5-fluorouracil and Cyclophosphamide.

Drug: Valproic acid; Drug: Epirubicin; Drug: 5-fluorouracil; Drug: Cyclophosphamide.

Interventions

Valproic acid DRUG

Beginning Dose, Level 1: 15 mg/kg/day.

Also known as: Valproic, Depakote, VPA

Dose Escalation and Possible Expansion

Epirubicin DRUG

Beginning Dose, Level 1: 75 mg/m\^2.

Also known as: Ellence

Dose Escalation and Possible Expansion

5-fluorouracil DRUG

For breast cancer participants treated at MTD of Valproic acid and Epirubicin: 5-fluorouracil 500 mg/m\^2.

Also known as: 5-FU

Dose Escalation and Possible Expansion

Cyclophosphamide. DRUG

For breast cancer participants treated at MTD of Valproic acid and Epirubicin: cyclophosphamide 500 mg/m\^2.

Also known as: CYTOXAN®

Dose Escalation and Possible Expansion

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• National Cancer Institute (NCI): collaborator
• Pfizer: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Valproic Acid; Epirubicin; Fluorouracil; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Pamela Munster, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

• Adil Daud, MD

  H. Lee Moffitt Cancer Center and Research Institute

  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: October 28, 2005
• First Posted: October 31, 2005
• Study Start: March 1, 2004
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: February 23, 2017

Record last verified: 2009-01

Locations

US (1)