Clinical trial NCT00979992: Sunitinib Malate in Treating Patients With Persistent or Recurrent Clear Cell Ovarian Cancer
Official title: A Phase II Evaluation of SU11248 (Sunitinib Malate) (NSC #736511) in the Treatment of Persistent or Recurrent Clear Cell Ovarian Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Clear Cell Adenocarcinoma
Recurrent Ovarian Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: NRG Oncology
First posted: 2009-09-18
Enrollment: 35
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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 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

Primary outcomes:
measure: Objective Tumor Response Rate (Complete and Partial Response)
timeFrame: CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; then every 3 months x 2; then every 6 months thereafter until disease progression for up to 5 years.
measure: The Percentage of Patients Who Survive Progression Free for at Least 6 Months
timeFrame: CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually, for a total duration of 8.25 years
measure: Progression-free Survival
timeFrame: Tumor scans were done every other cycle for the first 6 months; then every 3 months x 2; then every 6 months thereafter for up to 5 years.
measure: Number of Participants With Grade 3 or Higher Adverse Events
timeFrame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up.
Other outcomes:
measure: Change in Pro-angiogenic Protein Levels
timeFrame: Baseline to up to 5 years
measure: Changes in Serum and Plasma Angiogenesis Markers by Enzyme-linked Immunosorbent Assays
timeFrame: Baseline to up to 5 years
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center/Disney Family Cancer Center
state: California
city: Concord
country: United States
facility: John Muir Medical Center-Concord Campus
state: California
city: Los Angeles
country: United States
facility: Los Angeles County-USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: Walnut Creek
country: United States
facility: John Muir Medical Center-Walnut Creek
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Hartford
country: United States
facility: Smilow Cancer Hospital Care Center at Saint Francis
state: Connecticut
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Hinsdale
country: United States
facility: Sudarshan K Sharma MD Limited-Gynecologic Oncology
state: Illinois
city: Elkhart
country: United States
facility: Elkhart Clinic
state: Indiana
city: Elkhart
country: United States
facility: Michiana Hematology Oncology PC-Elkhart
state: Indiana
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Saint Vincent Hospital and Health Care Center
state: Indiana
city: Kokomo
country: United States
facility: Community Howard Regional Health
state: Indiana
city: La Porte
country: United States
facility: IU Health La Porte Hospital
state: Indiana
city: Mishawaka
country: United States
facility: Michiana Hematology Oncology PC-Mishawaka
state: Indiana
city: Mishawaka
country: United States
facility: Saint Joseph Regional Medical Center-Mishawaka
state: Indiana
city: Plymouth
country: United States
facility: Michiana Hematology Oncology PC-Plymouth
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: Michiana Hematology Oncology PC-South Bend
state: Indiana
city: South Bend
country: United States
facility: South Bend Clinic
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Westville
country: United States
facility: Michiana Hematology Oncology PC-Westville
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic PC - Ames
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Portland
country: United States
facility: Maine Medical Center-Bramhall Campus
state: Maine
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium NCORP
state: Michigan
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Dearborn
country: United States
facility: Beaumont Hospital - Dearborn
state: Michigan
city: Detroit
country: United States
facility: Ascension Saint John Hospital
state: Michigan
city: Escanaba
country: United States
facility: Green Bay Oncology - Escanaba
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Blanc
country: United States
facility: Genesys Regional Medical Center
state: Michigan
city: Iron Mountain
country: United States
facility: Green Bay Oncology - Iron Mountain
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Livonia
country: United States
facility: Saint Mary Mercy Hospital
state: Michigan
city: Niles
country: United States
facility: Lakeland Hospital Niles
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Lake Huron Medical Center
state: Michigan
city: Saginaw
country: United States
facility: Ascension Saint Mary's Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Medical Center Saint Joseph
state: Michigan
city: Saint Joseph
country: United States
facility: Marie Yeager Cancer Center
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Cancer Research for the Ozarks NCORP
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Reno
country: United States
facility: Center of Hope at Renown Medical Center
state: Nevada
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Concord
country: United States
facility: Atrium Health Cabarrus/LCI-Concord
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center/Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital Cancer Center
state: Ohio
city: Mentor
country: United States
facility: UH Seidman Cancer Center at Lake Health Mentor Campus
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute-Tulsa
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Hazleton
country: United States
facility: Geisinger Medical Center-Cancer Center Hazleton
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley/Henry Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Parkland Memorial Hospital
state: Texas
city: Dallas
country: United States
facility: Clements University Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Green Bay
country: United States
facility: Green Bay Oncology at Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology Limited at Saint Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital Cancer Center at Saint Mary's
state: Wisconsin
city: Manitowoc
country: United States
facility: Holy Family Memorial Hospital
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Saint Vincent Hospital Cancer Center at Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology - Sturgeon Bay
state: Wisconsin
city: West Allis
country: United States
facility: Aurora West Allis Medical Center
state: Wisconsin
city: Jung-Ku
country: Korea, Republic of
facility: Keimyung University-Dongsan Medical Center
state: Daegu
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Korea
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea Cancer Center Hospital
Study officials:
affiliation: NRG Oncology
name: John K Chan
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.