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Treatment With ATRA-IV and Depakote in Patients With Advanced Solid Tumor Malignancies

Phase 1
Terminated
Conditions
Solid Tumor Malignancies
Registration Number
NCT00195156
Lead Sponsor
Weill Medical College of Cornell University
Brief Summary

The purpose of this study is to find out the highest tolerated dose of Depakote in combination with liposome encapsulated all-trans retinoic acid (ATRA-IV) in patients with advanced solid tumor malignancies.

Detailed Description

To determine the maximum tolerated dose of Depakote in combination with liposome encapsulated all-trans retinoic acid (ATRA-IV) in patients with advanced solid tumor malignancies.

This will be a 2-step dose escalation study. Once the patient starts therapy at a designated dose level, it will not be escalated for that patient. Three patients at each dose level must complete 4 weeks of therapy before escalating to the next higher level. If none of the patients experience dose limiting toxicity (DLT), then 3 new patients will be treated with the next higher dose level.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Patients with histologic confirmation of a solid tumor malignancy with clinical evidence of metastatic disease.
  • Patients must have failed at least one standard therapy, if available, for their malignancy. Patients may be entered on the trial without prior therapy if there is no standard effective therapy available.
  • No active brain metastases or epidural tumor.
Exclusion Criteria
  • Concomitant administration of steroids.
  • Irradiation or chemotherapy within 14 days of start of protocol.
  • Evidence of another active cancer, except for non-melanoma, carcinoma of the skin and in-situ carcinoma of the cervix curatively treated, Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for greater than 5 years.
  • Women who are pregnant or lactating. Women or men of reproductive age who are unwilling to use two forms of effective contraception.
  • Patients with clinically significant cardiac, renal or hepatic disease; severe debilitating pulmonary disease; or history of diabetes mellitus prone to ketoacidosis.
  • Patients with a history of pancreatitis.
  • Patients with known hypersensitivity to retinoids or retinoic acid derivatives.
  • Patients with coagulation disorders, such as thrombophlebitis or pulmonary embolism.
  • Patients with pre-existing psychiatric condition, especially depression or a history of severe uncontrolled psychiatric disorder.
  • Patients with pre-existing thyroid abnormalities whose thyroid function cannot be maintained in the normal range.
  • Patients with chronic moderate to severe nausea.
  • Patients with history of epilepsy or a seizure disorder taking anti-convulsant medication.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
To determine the maximum tolerated dose of Depakote in combination with liposome encapsulated all-trans retinoic acid (ATRA-IV) in patients with advanced solid tumor malignancies.
To define the dose limiting and other toxicities of the combination therapy
To determine the dosing that should be used in future safety and efficacy (Phase II) trials
Secondary Outcome Measures
NameTimeMethod
To study retinoic acid receptor expression and histone acetylation status to ascertain biologic effect on peripheral blood mononuclear cells and tissue obtained from selected patients who undergo tumor biopsies.
To assess for tumor responses to combination therapy.

Trial Locations

Locations (1)

Weill Medical College of Cornell University

🇺🇸

New York, New York, United States

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