Sunitinib Malate in Treating Patients With Persistent or Recurrent Clear Cell Ovarian Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00979992
First received: September 17, 2009
Last updated: September 23, 2014
Last verified: May 2014
  Purpose

This phase II trial studies the side effects of sunitinib malate and how well it works in treating patients with persistent or recurrent ovarian cancer. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.


Condition Intervention Phase
Ovarian Clear Cell Cystadenocarcinoma
Recurrent Ovarian Epithelial Cancer
Drug: sunitinib malate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of SU11248 (Sunitinib Malate) (NSC #736511) in the Treatment of Persistent or Recurrent Clear Cell Ovarian Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective tumor response rate (complete and partial response) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Progression-free survival rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of progression-free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.

  • Duration of overall survival [ Time Frame: From start of treatment to time of death or the date of last contact, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.

  • Incidence of adverse effects as assessed with the active version of the Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Change in pro-angiogenic protein levels [ Time Frame: Baseline to up to 5 years ] [ Designated as safety issue: No ]
  • Changes in serum and plasma angiogenesis markers by enzyme-linked immunosorbent assays [ Time Frame: Baseline to up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 53
Study Start Date: April 2010
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (sunitinib malate)
Patients receive sunitinib malate PO QD for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: sunitinib malate
Given PO
Other Names:
  • SU11248
  • sunitinib
  • Sutent
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the anti-tumor activity of SU11248 (sunitinib malate), a highly potent, selective tyrosine kinases inhibitor, in patients with persistent or recurrent clear cell ovarian carcinoma II. To examine the nature and degree of toxicity in this cohort of patients treated with this regimen.

SECONDARY OBJECTIVES:

I. To characterize the distribution of progression-free survival and overall survival for patients treated with SU11248 (sunitinib malate).

TERTIARY OBJECTIVES:

I. To determine the pre-cycle 1, pre-cycle 4 and off-treatment levels of pro-angiogenic proteins (e.g., angiogenin, soluble vascular cell adhesion molecule [VCAM]-I, basic fibroblast growth factor [bFGF], platelet-derived growth factor [PDGF], placental growth factor [PlGF], vascular endothelial growth factor [VEGF], and hypoxia-inducible factor [HIF]1alpha).

II. To identify changes in serum and plasma angiogenesis markers at baseline (pre-cycle 1), during treatment (cycle 4), and at progression in association with primary and secondary clinical endpoints associated with clinical response or progression-free survival.

OUTLINE:

Patients receive sunitinib malate orally (PO) once daily (QD) for 4 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have recurrent or persistent clear cell ovarian cancer; primary tumors must be at least 50% clear cell histomorphology in order to be eligible or have a histologically documented recurrence with at least 50% clear cell histomorphology; in addition, the tumors should be negative for expression of Wilms tumor (WT)-1 antigen and estrogen receptor (ER) antigen by immunohistochemistry; appropriate tissue sections must be available for histologic evaluation for central pathology review by Gynecologic Oncology Group (GOG); immunohistochemical stained slides for ER and WT-1 antigen must be available for review by GOG

    • If the primary tumor had at least 50% clear cell histomorphology, a biopsy of the recurrent or persistent tumor is not required; however, immunohistochemical studies of the primary tumor for ER and WT-1 antigens should be performed and the slides submitted to the GOG for review; the percentage of clear cell histomorphology must be documented in the pathology report or in an addendum to the original report; if slides of the primary tumor are not available for review due to disposal of slides by the histology laboratory (typically 10 years after diagnosis), biopsy of recurrent or persistent disease is required
    • If the primary tumor had less than 50% clear cell histomorphology (or if slides of the primary tumor are not available for review), a biopsy of the recurrent or persistent tumor is required to confirm at least 50% clear cell histomorphology and lack of immunoreactivity for ER and WT-1 antigens by immunohistochemistry; the percentage of involvement must be documented in the pathology report or in an addendum to the original report
  • All patients must have measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
  • Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy; thus, a confirmed biopsy in an irradiated area at a date longer than 90 days post-completion of radiation can be considered a target lesion to assess progression and response
  • Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment
  • Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition:

    • Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa
  • Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease) must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy
  • Patients may have received prior biologic therapy, but must not have had any prior therapy with agents which inhibit VEGF, vascular endothelial growth factor receptor (VEGFR) or PDGF such as, bevacizumab, sorafenib, sunitinib, pazopanib, brivanib, aflibercept cediranib, BIBF 1120, imatinib, dasatinib
  • Any other prior therapy directed at the malignant tumor, including immunologic agents (e.g. tamoxifen) must be discontinued at least three weeks prior to registration
  • Patients must not be eligible for a higher priority (e.g.; Phase III), GOG protocol for the same population if one exists
  • Patients must be recovered from effects of recent surgery (28 days must elapse between surgery and the start of treatment with sunitinib malate)
  • Patents must have >= 4 weeks since prior chemotherapy or radiation (>= 6 weeks for nitrosoureas or mitomycin C)
  • Sunitinib metabolizes via liver enzyme, specifically the cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) enzyme; therefore, potential drug interaction with the CYP3A4 enzyme can occur; eligible patients who are on the CYP3A4 inducer or inhibitor enzyme should stop 2 weeks prior to study entry if all other eligibility has been confirmed; the principal investigator will review the case and make all effort to switch such agent to other medication
  • Patients should be free of active infection (with the exception of uncomplicated urinary tract infections [UTI]) requiring antibiotics
  • Patients who have received one prior regimen must have a GOG performance status of 0, 1 or 2; patients who have received two prior regimens must have GOG performance status of 0 or 1
  • Absolute neutrophil count (ANC) >= 1,500/mcl
  • Platelets greater than or equal 100,000/mcl
  • Creatinine less than or equal to 1.5 times the upper limit of normal (ULN)
  • Bilirubin less than or equal to 1.5 ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 times the ULN, unless subjects have liver metastasis, in which case both AST and ALT must be less than or equal to 5 times the ULN
  • Patients who have met the pre-entry requirements
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

  • Primary peritoneal or fallopian tube primaries are not eligible
  • Patients with serious non-healing wound, ulcer, or bone fracture
  • Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
  • Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within 6months of the first date of treatment on this study
  • Patients with clinically significant cardiovascular disease; this includes:

    • Poorly controlled hypertension (systolic blood pressure of >= 140 mm Hg or diastolic blood pressure of >= 90 mm Hg) are ineligible
    • Myocardial infarction or unstable angina within 6 months prior to registration
    • New York Heart Association (NYHA) grade II or greater congestive heart failure
    • Cardiac arrhythmia requiring medication
    • Grade II or greater peripheral vascular disease based on National Cancer Institute Common Terminology Criteria (NCI CTC); e.g. ischemic rest pain, minor tissue loss, and ulceration or gangrene
  • Patients with QTc prolongation (> 500 msec) are excluded
  • Patients who require use of therapeutic doses of Coumadin-derivative anticoagulants such as warfarin are ineligible, although doses of up to 2 mg daily are permitted for prophylaxis of thrombosis; low molecular weight heparin is permitted provided patient's prothrombin time (PT) international normalized ratio (INR) is =< 1.5
  • Patients with clinically significant peripheral artery disease, e.g., those with claudication, within 6 months
  • Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible; patients with a history of hypothyroidism are eligible provided they are currently euthyroid
  • Patients whose circumstances do not permit completion of the study or the required follow-up
  • Patients who are pregnant or nursing; to date, no fetal studies in animals or humans have been performed; the possibility of harm to a fetus is likely; this drug specifically inhibits VEGF, which is responsible for formation of new blood vessels during development, and antibodies can cross the placenta; therefore, it should not be administered to pregnant women; subjects will be apprised of the large potential risk to a developing fetus; it is not known whether the drug is excreted in human milk; because many drugs are excreted in human milk, this drug should not be administered to nursing women; women of childbearing potential must agree to use contraceptive measures during study therapy and for at least 3 months after completion of therapy; a negative serum pregnancy test within 72 hours of starting drug is required
  • Patients who have a major surgical procedure, or significant traumatic injury within 28 days prior to the first date of treatment on this study, or anticipation of need for major surgical procedure during the course of the study; patients with placement of vascular access device or core biopsy within 7 days prior to the first date of treatment on this study
  • Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy
  • Patients who have received prior therapy with this drug
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00979992

  Show 95 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: John Chan NRG Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00979992     History of Changes
Other Study ID Numbers: NCI-2011-03811, NCI-2011-03811, CDR0000654556, GOG-0254, GOG-0254, U10CA027469, U10CA180868
Study First Received: September 17, 2009
Last Updated: September 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystadenocarcinoma
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Adenocarcinoma
Adnexal Diseases
Carcinoma
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Cystic, Mucinous, and Serous
Ovarian Diseases
Urogenital Neoplasms
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014