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

NCT ID: NCT00979992

Last Updated: 2020-02-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-04-19

Study Completion Date

2019-02-09

Brief Summary

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This phase II trial studies the side effects of sunitinib malate and how well it works in treating patients with ovarian cancer that is persistent or has come back. 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.

Detailed Description

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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.

Conditions

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Ovarian Clear Cell Adenocarcinoma Recurrent Ovarian Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Sunitinib Malate

Intervention Type DRUG

Given PO

Interventions

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Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Sunitinib Malate

Given PO

Intervention Type DRUG

Other Intervention Names

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SU011248 SU11248 sunitinib Sutent

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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NRG Oncology

OTHER

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John K Chan

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

Site Status

John Muir Medical Center-Concord Campus

Concord, California, United States

Site Status

Los Angeles County-USC Medical Center

Los Angeles, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCSF Medical Center-Mount Zion

San Francisco, California, United States

Site Status

John Muir Medical Center-Walnut Creek

Walnut Creek, California, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Northside Hospital

Atlanta, Georgia, United States

Site Status

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, United States

Site Status

Sudarshan K Sharma MD Limited-Gynecologic Oncology

Hinsdale, Illinois, United States

Site Status

Elkhart Clinic

Elkhart, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Elkhart

Elkhart, Indiana, United States

Site Status

Elkhart General Hospital

Elkhart, Indiana, United States

Site Status

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, United States

Site Status

Community Howard Regional Health

Kokomo, Indiana, United States

Site Status

IU Health La Porte Hospital

La Porte, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Mishawaka

Mishawaka, Indiana, United States

Site Status

Saint Joseph Regional Medical Center-Mishawaka

Mishawaka, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Plymouth

Plymouth, Indiana, United States

Site Status

Memorial Hospital of South Bend

South Bend, Indiana, United States

Site Status

Michiana Hematology Oncology PC-South Bend

South Bend, Indiana, United States

Site Status

South Bend Clinic

South Bend, Indiana, United States

Site Status

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Site Status

Michiana Hematology Oncology PC-Westville

Westville, Indiana, United States

Site Status

McFarland Clinic PC - Ames

Ames, Iowa, United States

Site Status

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Site Status

Maine Medical Center-Bramhall Campus

Portland, Maine, United States

Site Status

Michigan Cancer Research Consortium NCORP

Ann Arbor, Michigan, United States

Site Status

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Site Status

Beaumont Hospital - Dearborn

Dearborn, Michigan, United States

Site Status

Ascension Saint John Hospital

Detroit, Michigan, United States

Site Status

Green Bay Oncology - Escanaba

Escanaba, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Genesys Regional Medical Center

Grand Blanc, Michigan, United States

Site Status

Green Bay Oncology - Iron Mountain

Iron Mountain, Michigan, United States

Site Status

Allegiance Health

Jackson, Michigan, United States

Site Status

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

Borgess Medical Center

Kalamazoo, Michigan, United States

Site Status

Sparrow Hospital

Lansing, Michigan, United States

Site Status

Saint Mary Mercy Hospital

Livonia, Michigan, United States

Site Status

Lakeland Hospital Niles

Niles, Michigan, United States

Site Status

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Site Status

Lake Huron Medical Center

Port Huron, Michigan, United States

Site Status

Ascension Saint Mary's Hospital

Saginaw, Michigan, United States

Site Status

Lakeland Medical Center Saint Joseph

Saint Joseph, Michigan, United States

Site Status

Marie Yeager Cancer Center

Saint Joseph, Michigan, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Cancer Research for the Ozarks NCORP

Springfield, Missouri, United States

Site Status

Mercy Hospital Springfield

Springfield, Missouri, United States

Site Status

CoxHealth South Hospital

Springfield, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Site Status

Center of Hope at Renown Medical Center

Reno, Nevada, United States

Site Status

Renown Regional Medical Center

Reno, Nevada, United States

Site Status

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Site Status

Atrium Health Cabarrus/LCI-Concord

Concord, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Riverside Methodist Hospital

Columbus, Ohio, United States

Site Status

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, United States

Site Status

UH Seidman Cancer Center at Lake Health Mentor Campus

Mentor, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, United States

Site Status

Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Geisinger Medical Center-Cancer Center Hazleton

Hazleton, Pennsylvania, United States

Site Status

Geisinger Medical Group

State College, Pennsylvania, United States

Site Status

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania, United States

Site Status

Women and Infants Hospital

Providence, Rhode Island, United States

Site Status

Parkland Memorial Hospital

Dallas, Texas, United States

Site Status

Clements University Hospital

Dallas, Texas, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Green Bay Oncology at Saint Vincent Hospital

Green Bay, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

Site Status

Green Bay Oncology Limited at Saint Mary's Hospital

Green Bay, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center at Saint Mary's

Green Bay, Wisconsin, United States

Site Status

Holy Family Memorial Hospital

Manitowoc, Wisconsin, United States

Site Status

Bay Area Medical Center

Marinette, Wisconsin, United States

Site Status

Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center at Oconto Falls

Oconto Falls, Wisconsin, United States

Site Status

Green Bay Oncology - Sturgeon Bay

Sturgeon Bay, Wisconsin, United States

Site Status

Aurora West Allis Medical Center

West Allis, Wisconsin, United States

Site Status

Keimyung University-Dongsan Medical Center

Jung-Ku, Daegu, South Korea

Site Status

Samsung Medical Center

Seoul, Korea, South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Gangnam Severance Hospital

Seoul, , South Korea

Site Status

Korea Cancer Center Hospital

Seoul, , South Korea

Site Status

Countries

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United States South Korea

References

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Chan JK, Brady W, Monk BJ, Brown J, Shahin MS, Rose PG, Kim JH, Secord AA, Walker JL, Gershenson DM. A phase II evaluation of sunitinib in the treatment of persistent or recurrent clear cell ovarian carcinoma: An NRG Oncology/Gynecologic Oncology Group Study (GOG-254). Gynecol Oncol. 2018 Aug;150(2):247-252. doi: 10.1016/j.ygyno.2018.05.029. Epub 2018 Jun 18.

Reference Type DERIVED
PMID: 29921512 (View on PubMed)

Other Identifiers

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NCI-2011-03811

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000654556

Identifier Type: -

Identifier Source: secondary_id

GOG-0254

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0254

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180868

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA027469

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-03811

Identifier Type: -

Identifier Source: org_study_id

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