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SU5416 and Carboplatin to Treat Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT00006155
Recruitment Status : Completed
First Posted : December 10, 2002
Last Update Posted : March 4, 2008
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Fallopian Tube Neoplasm Ovarian Cancer Peritoneal Neoplasm Drug: SU5416 and carboplatin Phase 1

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  (Clinical Trial)
Enrollment : 33 participants
Primary Purpose: Treatment
Official Title: A Phase I Study of SU5416, an Antiangiogenesis Agent, in Combination With Carboplatin in Patients With Platinum-Refractory Ovarian Cancer
Study Start Date : August 2000
Study Completion Date : April 2001

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer
Drug Information available for: Carboplatin





Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006155


Locations
United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)

Publications:
ClinicalTrials.gov Identifier: NCT00006155     History of Changes
Other Study ID Numbers: 000197
00-C-0197
First Posted: December 10, 2002    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: June 2000

Keywords provided by National Institutes of Health Clinical Center (CC):
DNA Damage
DNA Repair
FLK-1
Pharmacokinetics
VEGF
Fallopian Tube Cancer
Ovarian Cancer
Platinum-Refractory Disease

Additional relevant MeSH terms:
Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Semaxinib
Carboplatin
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action