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

Phase 2

Completed

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

Interventions: Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Selumetinib
Drug: Selumetinib Sulfate

Registration Number: NCT00551070

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 52

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (selumetinib sulfate)	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.
Treatment (selumetinib sulfate)	Pharmacological Study	Patients receive selumetinib sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (selumetinib sulfate)	Laboratory Biomarker Analysis	Patients receive selumetinib sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (selumetinib sulfate)	Selumetinib	Patients receive selumetinib sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Adverse Events (Grade 3 or Higher) During First Cycle of Treatment	Cycle 1
Tumor Response	Every other cycle	Complete and Partial Tumor Response by (Response Evaluation Criteria in Solid Tumors) RECIST 1.0
Area Under the Curve (AUC) for AZD6244, 100 mg Administered Orally Twice Daily.	Pre-dose, and 1, 3, and 6 hours after administration of drug on Day 7 after the start of AZD6244 treatment
Maximum Concentration (Cmax) for AZD6244, 100 mg Administered Orally Twice Daily.	Pre-dose, and 1, 3, and 6 hours after administration of drug on Day 7 after the start of AZD6244 treatment

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	Every other cycle
Number of Courses Received	Every cycle
Overall Survival	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 the next 5 years

Trial Locations

Locations (49): Maine Medical Center-Bramhall Campus
🇺🇸
Portland, Maine, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
🇺🇸
Columbus, Ohio, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
The Hospital of Central Connecticut
🇺🇸
New Britain, Connecticut, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸
Newark, Delaware, United States
Christiana Care - Union Hospital
🇺🇸
Elkton, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Holland Community Hospital
🇺🇸
Holland, Michigan, United States
Mercy Health Mercy Campus
🇺🇸
Muskegon, Michigan, United States
Mercy Hospital Springfield
🇺🇸
Springfield, Missouri, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
USC / Norris Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Stanford Cancer Institute Palo Alto
🇺🇸
Palo Alto, California, United States
Hinsdale Hematology Oncology Associates Incorporated
🇺🇸
Hinsdale, Illinois, United States
University of Chicago Comprehensive Cancer Center
🇺🇸
Chicago, Illinois, United States
Saint Vincent Hospital and Health Care Center
🇺🇸
Indianapolis, Indiana, United States
Bronson Battle Creek
🇺🇸
Battle Creek, Michigan, United States
Spectrum Health Big Rapids Hospital
🇺🇸
Big Rapids, Michigan, United States
Spectrum Health at Butterworth Campus
🇺🇸
Grand 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
Munson Medical Center
🇺🇸
Traverse City, Michigan, United States
Metro Health Hospital
🇺🇸
Wyoming, Michigan, United States
Mercy Health Partners-Hackley Campus
🇺🇸
Muskegon, Michigan, United States
CoxHealth South Hospital
🇺🇸
Springfield, Missouri, United States
Cancer Research for the Ozarks NCORP
🇺🇸
Springfield, Missouri, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸
Charlotte, North Carolina, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Cooper Hospital University Medical Center
🇺🇸
Camden, New Jersey, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
Novant Health Presbyterian Medical Center
🇺🇸
Charlotte, North Carolina, United States
Gynecologic Oncology Network
🇺🇸
Greenville, North Carolina, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸
Cleveland, Ohio, United States
Mount Carmel Health Center West
🇺🇸
Columbus, Ohio, United States
Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Hillcrest Hospital Cancer Center
🇺🇸
Mayfield Heights, Ohio, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
🇺🇸
Mentor, Ohio, United States
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
🇺🇸
Tulsa, Oklahoma, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States