SU5416 and Carboplatin to Treat Ovarian Cancer

March 3, 2008 updated by: National Cancer Institute (NCI)

A Phase I Study of SU5416, an Antiangiogenesis Agent, in Combination With Carboplatin in Patients With Platinum-Refractory Ovarian Cancer

SU5416, a novel antiangiogenesis agent, has been shown to be a potent and selective inhibitor of the tyrosine kinase activity of FlK-1 (a downstream effector of VEGF) in vitro and to inhibit the growth of endothelial cells. Since VEGF mRNA levels and vessel counts in tumor tissues have been shown to be inversely related to prognosis in ovarian cancer, SU5416 may prove to be a useful agent in this disease. Platinum agents currently provide the most effective treatment for ovarian cancer. However, ovarian cancer often becomes refractory to platinum therapy, leaving the patient with a poor prognosis. This is a phase I study designed to: a) determine a dose level of carboplatin to use in combination with an established dose of SU5416 for treatment of patients with platinum-refractory ovarian cancer, b) assess the side effect profile of SU5416 and carboplatin combination therapy, c) characterize any alterations in SU5416 pharmacokinetic and pharmacodynamic parameters when given in combination with carboplatin, d) characterize carboplatin pharmacokinetic and pharmacodynamic parameters when given in combination with SU5416, e) do exploratory studies to assess the effect of SU5416 on platinum-DNA adduct levels, f) do exploratory studies to assess any alterations in ERCC1 mRNA levels when carboplatin is administered with SU5416, and g) obtain preliminary evidence of the ability of SU5416 to reverse platinum resistance in patients with platinum-refractory ovarian carcinoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

SU5416, a novel antiangiogenesis agent, has been shown to be a potent and selective inhibitor of the tyrosine kinase activity of FlK-1 (a downstream effector of VEGF) in vitro and to inhibit the growth of endothelial cells. Since VEGF mRNA levels and vessel counts in tumor tissues have been shown to be inversely related to prognosis in ovarian cancer, SU5416 may prove to be a useful agent in this disease. Platinum agents currently provide the most effective treatment for ovarian cancer. However, ovarian cancer often becomes refractory to platinum therapy, leaving the patient with a poor prognosis. This is a phase I study designed to: a) determine a dose level of carboplatin to use in combination with an established dose of SU5416 for treatment of patients with platinum-refractory ovarian cancer, b) assess the side effect profile of SU5416 and carboplatin combination therapy, c) characterize any alterations in SU5416 pharmacokinetic and pharmacodynamic parameters when given in combination with carboplatin, d) characterize carboplatin pharmacokinetic and pharmacodynamic parameters when given in combination with SU5416, e) do exploratory studies to assess the effect of SU5416 on platinum-DNA adduct levels, f) do exploratory studies to assess any alterations in ERCC1 mRNA levels when carboplatin is administered with SU5416, and g) obtain preliminary evidence of the ability of SU5416 to reverse platinum resistance in patients with platinum-refractory ovarian carcinoma.

Study Type

Interventional

Enrollment

33

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Cancer Institute (NCI)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Must have histopathologically documented epithelial ovarian carcinoma confirmed in the Laboratory of Pathology, at the National Cancer Institute prior to starting this study. Also eligible will be patients with the histologic diagnosis of: Recurrent primary fallopian tube cancers; Recurrent primary peritoneal cancers (non-mesothelioma).

Must have either measurable disease by physical exam or radiographic imaging, or patients must have evaluable disease. Evaluable disease will include patients with third-space fluid accumulations that are proven to be positive for adenocarcinoma; and patients with an elevated CA125 above 100 IU per mL.

Must have platinum-refractory disease (persistent or recurrent disease within 6 months of last cisplatin or carboplatin therapy).

Must have a life expectancy of more than 2 months.

Must have an ECOG performance status of 0, 1, or 2.

No patients with medical or surgical complications requiring immediate intervention, but may enroll after resolution of the acute problem (e.g. impending bowel obstruction, active infection, etc.).

PT and PTT must be less than 1.5 times the upper limit of normal.

Must have recovered from any toxicity related to prior therapy to NCI/CTEP Grade 0, or 1, with the exception of peripheral neuropathy, in which case grade 2 toxicity is permissible.

Granulocyte count must be greater than or equal to 1,500/mm(3).

Hemoglobin must be greater than or equal to 9.0 g/dL (pre-treatment transfusion is allowed, provided the hemoglobin is maintained for more than seven days and/or active source of bleeding is identified and treated).

Platelet count must be greater than or equal to 100,000/mm(3).

Acute care panel (electrolytes, BUN) and urinalysis should be considered normal for each patient in the judgement of the clinic attending (blood glucose is excluded from this evaluation). No gross abnormalities should be present. "Normal" will be defined as the normal range for that test in the facility where the test was taken.

Hepatic function: normal bilirubin (total); ALT less than 2 times the upper limit of normal; AST less than 2 times the upper limit of normal.

Must be capable of understanding and signing an informed consent form.

Must be willing to travel from their home to the NIH for follow-up visits.

Must be greater than or equal to 18 years of age.

Must be able and willing to follow instructions and conform to protocol.

Prior chemotherapy must have been stopped at least 4 weeks prior to enrollment. Mitomycin C and nitrosoureas should have been stopped at least 6 weeks prior to enrollment.

Must have failed no more than three prior chemotherapy regimens. Retreatment of patients who were initially sensitive to platinum with either the same regimen or platinum as a single agent would only constitute one prior regimen.

No history of external beam radiation.

Patients capable of childbearing must use effective birth control while on the study.

No non-skin malignancy or melanoma within the past 5 years.

No active infection, including positive serology for HIV. Patients on suppressive antibiotic therapy will be evaluated on a case-by-case basis.

No history of brain metastases.

No uncompensated coronary artery disease on electrocardiogram or physical examination, or a history of myocardial infarction or severe/unstable angina in the past 6 months. No diabetes mellitus with severe peripheral vascular disease and no deep venous or arterial thrombosis (including pulmonary embolism) within 3 months of entry. No New York class II-IV congestive heart failure, chronic obstructive lung disease requiring oxygen therapy or medication, or uncontrolled seizure activity. Uncomplicated asthma will be allowed. No active therapy for angina.

Must not have undergone a bone marrow transplant regimen.

No pregnant or breastfeeding individuals.

Must not have non-cancer life-threatening illnesses, including untreated infection (must be at least 1 week off antibiotic therapy before beginning cycle 1 of SU5416).

No non-epithelial histologies.

No peripheral neuropathy, NCI CTEP grade 3 or 4.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2000

Study Completion

April 1, 2001

Study Registration Dates

First Submitted

August 9, 2000

First Submitted That Met QC Criteria

December 9, 2002

First Posted (Estimate)

December 10, 2002

Study Record Updates

Last Update Posted (Estimate)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

June 1, 2000

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 000197
  • 00-C-0197

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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