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Neoplasms, AdvancedPhase 1NCT00246103

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

A Phase 1 study testing Valproic acid, Epirubicin and 5-fluorouracil in people with Neoplasms, Advanced, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms, Advanced
What is being tested?
Valproic acid, Epirubicin and 5-fluorouracil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
82 participants
Where
1 siteUnited States
Study dates
Mar 2004to Apr 2008
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

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.

Read the 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 anti-convulsant or to treat migraine headaches. Recommended concentrations for seizure control is 15-60 mg/kg. Pharmacokinetic studies from healthy volunteers and patients suggested a linear increase in plasma concentrations. A daily dosing of 16 mg/kg divalproex (delayed-release VPA) resulted in a peak VPA plasma concentration of 127 μg/ml (~0.9 mM) 27. The recommended Phase II dose of VPA was 60 mg/kg/d when given by a one-hour intravenous infusion twice daily for 5 days every three weeks.

Synergistic activity between VPA and epirubicin has been observed at 0.5 mM of VPA in our preclinical laboratory studies. Patients will receive an intravenous loading dose of VPA followed by divalproex in two daily doses for 5 doses. The loading dose of VPA will avoid a delay in peak plasma concentrations and excessive nausea. Epirubicin will be given by infusion on day 3 after the last dose of divalproex.

Once the MTD for this two drug regimen has been determined, the maximum tolerated dose will be determined as part of the FEC regimen (5-fluorouracil, epirubicin and cyclophosphamide).

Being tested
Valproic acid, Epirubicin, 5-fluorouracil, Cyclophosphamide.
Keywords
Valproic Acid, Epirubicin, Solid Tumor, Malignancies
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Valproic acidDrug

    Also called Valproic, Depakote, VPA

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

  • EpirubicinDrug

    Also called Ellence

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

  • 5-fluorouracilDrug

    Also called 5-FU

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

  • Cyclophosphamide.Drug

    Also called CYTOXAN®

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

Study groups in NCT00246103
Study groupRoleWhat they receive
Dose Escalation and Possible ExpansionExperimentalEscalating 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.
Receives: Drug: Valproic acid; Drug: Epirubicin; Drug: 5-fluorouracil; Drug: Cyclophosphamide.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2005 (estimated)
  2. Study startMar 2004
  3. Primary completionApr 2008
  4. Study completionApr 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
82 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00246103
Sponsor's protocol ID
MCC-13693
Other IDs
USFIRB#101881
Status last verified
Jan 2009
First submitted
28 Oct 2005
Last updated
23 Feb 2017
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Valproic acid, Epirubicin and 5-fluorouracil in people with Neoplasms, Advanced, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: Up to 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00246103.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2017.

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