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

NCT00551070 | Completed Phase 2 Results

• 5 other identifiers: NCI-2009-00604CDR0000563965GOG-0239U10CA180868U10CA027469
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 49

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.

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

Outcome Measures

Primary Outcomes (4)

• Tumor Response

  Complete and Partial Tumor Response by (Response Evaluation Criteria in Solid Tumors) RECIST 1.0

  Every other cycle

• Adverse Events (Grade 3 or Higher) During First Cycle of Treatment

  Cycle 1

• 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 Outcomes (3)

• 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

Study Arms (1)

Treatment (selumetinib sulfate)

EXPERIMENTAL

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

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

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (selumetinib sulfate)

Pharmacological Study OTHER

Correlative studies

Treatment (selumetinib sulfate)

Selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD6244, MEK Inhibitor AZD6244

Treatment (selumetinib sulfate)

Selumetinib Sulfate DRUG

Given PO

Also known as: AZD-6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulphate, Koselugo, Selumetinib Sulphate

Treatment (selumetinib sulfate)

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• NRG Oncology: collaborator

Study Sites (49)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, 06050, United States

Location

Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

Christiana Care Health System-Christiana Hospital

Newark, Delaware, 19718, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Hinsdale Hematology Oncology Associates Incorporated

Hinsdale, Illinois, 60521, United States

Location

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, 46260, United States

Location

Maine Medical Center-Bramhall Campus

Portland, Maine, 04102, United States

Location

Christiana Care - Union Hospital

Elkton, Maryland, 21921, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Bronson Battle Creek

Battle Creek, Michigan, 49017, United States

Location

Spectrum Health Big Rapids Hospital

Big Rapids, Michigan, 49307, United States

Location

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, 49503, United States

Location

Mercy Health Saint Mary's

Grand Rapids, Michigan, 49503, United States

Location

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, 49503, United States

Location

Holland Community Hospital

Holland, Michigan, 49423, United States

Location

Mercy Health Partners-Hackley Campus

Muskegon, Michigan, 49442, United States

Location

Mercy Health Mercy Campus

Muskegon, Michigan, 49444, United States

Location

Munson Medical Center

Traverse City, Michigan, 49684, United States

Location

Metro Health Hospital

Wyoming, Michigan, 49519, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Cancer Research for the Ozarks NCORP

Springfield, Missouri, 65804, United States

Location

Mercy Hospital Springfield

Springfield, Missouri, 65804, United States

Location

CoxHealth South Hospital

Springfield, Missouri, 65807, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cooper Hospital University Medical Center

Camden, New Jersey, 08103, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States

Location

Gynecologic Oncology Network

Greenville, North Carolina, 27834, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Mount Carmel Health Center West

Columbus, Ohio, 43222, United States

Location

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, 44124, United States

Location

UH Seidman Cancer Center at Lake Health Mentor Campus

Mentor, Ohio, 44060, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, 74146, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 23261356 DERIVED

MeSH Terms

Conditions

Cystadenocarcinoma, Serous

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Cystadenocarcinoma; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Cystic, Mucinous, and Serous

Limitations and Caveats

Study began with 100mg BID mix \& drink (MD) formulation. AstraZeneca (AZ) switched to hydrogen-sulfate capsule (HC). AZ deemed 100mg BID MD equivalent to 50mg BID HC. As of 12/31/2010, patients got 50mg BID HC; four patients were on treatment then.

Results Point of Contact

• Title: Angela M. Kuras, Associate Director of Data Management
• Organization: NRG Oncology Statistics and Data Management Center - Buffalo

kurasa@nrgoncology.org

716-845-7733

Study Officials

• John H Farley

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2007
• First Posted: October 30, 2007
• Study Start: December 17, 2007
• Primary Completion: July 23, 2013
• Study Completion: November 13, 2020
• Last Updated: December 3, 2020
• Results First Posted: June 29, 2015

Record last verified: 2020-11

Locations

US (49)