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

Primary Peritoneal Carcinoma Clinical Trial

Official title:

A Phase II Trial of AZD6244 (NSC# 748727) in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary or Peritoneum

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00551070
• Other study ID #: NCI-2009-00604
• Secondary ID: NCI-2009-00604CD
• Status: Completed
• Phase: Phase 2
• Start date: December 17, 2007
• Est. completion date: November 13, 2020

Study information

• Verified date: November 2020
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: November 13, 2020
• Est. primary completion date: July 23, 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study
Correlative studies

Drug:
• Selumetinib
Given PO
• Selumetinib Sulfate
Given PO

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor Response	Complete and Partial Tumor Response by (Response Evaluation Criteria in Solid Tumors) RECIST 1.0	Every other cycle
Primary	Adverse Events (Grade 3 or Higher) During First Cycle of Treatment		Cycle 1
Primary	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
Primary	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	Progression-free Survival		Every other cycle
Secondary	Number of Courses Received		Every cycle
Secondary	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