Selumetinib Sulfate in Treating Woman With Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer

NCT ID: NCT00551070

Last Updated: 2020-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-17
• Study Completion Date: 2020-11-13

Brief Summary

This phase II trial studies the side effects and how well selumetinib sulfate works in treating patients with low-grade ovarian cancer that has come back (recurrent). Selumetinib sulfate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

I. To examine the tumor response rate of patients on AZD6244 (selumetinib sulfate) (NSC #748727).

II. To examine the acute toxicity of AZD6244 (NSC #748727) during the first course of treatment using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

III. To define the pharmacokinetic profile for AZD6244, 100 mg administered orally twice daily.

SECONDARY OBJECTIVES:

I. To examine the toxicity of AZD6244 (NSC #748727) using the 21 major categories of the CTCAE version 3.0.

II. To examine the dose and number of courses of AZD6244 (NSC #748727) given. III. To estimate the progression free survival, and overall survival of women receiving AZD6244 (NSC #748727).

TRANSLATIONAL RESEARCH OBJECTIVES:

I. To examine deoxyribonucleic acid (DNA) isolation with sequencing of braf, and ras mutation analysis and to explore their relationship with tumor response with AZD6244 (NSC #748727).

II. To examine protein levels of phosphorylated (p)-ERK/ERKERK) and explore their relationship with tumor response in patients treated with AZD6244 (NSC #748727).

OUTLINE:

Patients receive selumetinib sulfate orally (PO) twice a day (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for correlative and pharmacokinetic studies and to analyze selumetinib sulfate peak concentrations and the corresponding peak time values. Previously collected archived tumor tissue samples are obtained to determine protein levels of p-ERK/ERKERK, DNA isolation and sequencing of BRAF and ras mutation analysis by immunohistochemistry (IHC).

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year for 5 years.

Conditions

Borderline Ovarian Serous Tumor; Low Grade Ovarian Serous Adenocarcinoma; Micropapillary Serous Carcinoma; Primary Peritoneal Carcinoma; Primary Peritoneal Low Grade Serous Adenocarcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (selumetinib sulfate)

Patients receive selumetinib sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Selumetinib

Intervention Type: DRUG

Given PO

Selumetinib Sulfate

Intervention Type: DRUG

Given PO

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Selumetinib

Given PO

Intervention Type: DRUG

Selumetinib Sulfate

Given PO

Intervention Type: DRUG

Other Intervention Names

ARRY-142886; AZD6244; MEK Inhibitor AZD6244; AZD-6244 Hydrogen Sulfate; AZD6244 Hydrogen Sulfate; AZD6244 Hydrogen Sulphate; Koselugo; Selumetinib Sulphate

Eligibility Criteria

Inclusion Criteria

• Patients age greater than 18 with the following tumors are included in the study:

• Patients initially diagnosed with low-grade serous ovarian or peritoneal carcinoma that recur as low grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas as defined by Gynecologic Oncology Group [GOG], International Federation of Gynecology and Obstetrics [FIGO] World Health Organization [WHO] or Silverberg)
• Patients initially diagnosed with serous borderline ovarian or peritoneal carcinoma that recur as low grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas as defined by GOG, FIGO WHO or Silverberg)
• Patients must have measurable disease:

• Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each "target" lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or >= 10 mm when measured by spiral CT
• Patient must have documented low grade serous carcinoma (invasive micropapillary serous); confirmation must occur before patient is considered eligible for the trial

• Patients whose primary tumor was low-grade serous ovarian or peritoneal carcinoma must have a pretreatment sample of their tumor from their primary or recurrent tumor that documents low grade serous carcinoma (invasive micropapillary serous)
• Patients whose primary tumor was serous borderline ovarian or peritoneal carcinoma must have a pretreatment sample of their tumor from their recurrent tumor that documents low grade serous carcinoma (invasive micropapillary serous)
• Creatinine CTCAE grade 0-1 (< 1.5 x upper limit of normal [ULN])
• Bilirubin CTCAE grade 0-1 (< 1.5 x ULN)
• Transaminases CTCAE grade 0-1 (< 2.5 x ULN)
• Neutrophil CTCAE grade 0-1 (>= 1500/mcl)
• Platelets CTCAE grade 0-1 (>= 100,000/mcl)
• Neuropathy =< CTCAE grade 1
• No restrictions on prior therapy; patients cannot have previously received AZD6244
• Patients of childbearing potential must have a negative pregnancy test and must agree to practice an effective means of birth control prior to study entry, for the duration of study participation, and for four weeks after dosing with AZD6244 ceases
• Patients who have met the pre-entry requirements
• Patients must have signed an approved informed consent and authorization permitting release of personal health information
• Patients must have a GOG performance status of 0 or 1

Exclusion Criteria

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients may not be receiving any other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or its excipient Captisol
• Previous mitogen-activated protein kinase (MEK) inhibitor use
• Patients with corrected QT (QTc) interval > 450 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions are excluded
• Required use of a concomitant medication that can prolong the QT interval
• Patients should not receive any drugs known to affect or with the potential to affect selected CYP450 isoenzymes
• Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because the effects of AZD6244 on the developing human fetus at the recommended therapeutic dose are unknown; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with AZD6244
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD6244; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated

• Minimum Eligible Age: 19 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

NRG Oncology

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John H Farley

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Hartford Hospital

Hartford, Connecticut, United States

The Hospital of Central Connecticut

New Britain, Connecticut, United States

Beebe Medical Center

Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Hinsdale Hematology Oncology Associates Incorporated

Hinsdale, Illinois, United States

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, United States

Maine Medical Center-Bramhall Campus

Portland, Maine, United States

Christiana Care - Union Hospital

Elkton, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Bronson Battle Creek

Battle Creek, Michigan, United States

Spectrum Health Big Rapids Hospital

Big Rapids, Michigan, United States

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, United States

Mercy Health Saint Mary's

Grand Rapids, Michigan, United States

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

Holland Community Hospital

Holland, Michigan, United States

Mercy Health Partners-Hackley Campus

Muskegon, Michigan, United States

Mercy Health Mercy Campus

Muskegon, Michigan, United States

Munson Medical Center

Traverse City, Michigan, United States

Metro Health Hospital

Wyoming, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Cancer Research for the Ozarks NCORP

Springfield, Missouri, United States

Mercy Hospital Springfield

Springfield, Missouri, United States

CoxHealth South Hospital

Springfield, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Gynecologic Oncology Network

Greenville, North Carolina, United States

Case Western Reserve University

Cleveland, Ohio, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Riverside Methodist Hospital

Columbus, Ohio, United States

Mount Carmel Health Center West

Columbus, Ohio, United States

Miami Valley Hospital

Dayton, Ohio, United States

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, United States

UH Seidman Cancer Center at Lake Health Mentor Campus

Mentor, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Farley J, Brady WE, Vathipadiekal V, Lankes HA, Coleman R, Morgan MA, Mannel R, Yamada SD, Mutch D, Rodgers WH, Birrer M, Gershenson DM. Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol. 2013 Feb;14(2):134-40. doi: 10.1016/S1470-2045(12)70572-7. Epub 2012 Dec 21.

Reference Type: DERIVED

PMID: 23261356 (View on PubMed)

Other Identifiers

NCI-2009-00604

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000563965

Identifier Type: -

Identifier Source: secondary_id

GOG-0239

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0239

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-2009-00604

Identifier Type: -

Identifier Source: org_study_id