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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00551070
First received: October 22, 2007
Last updated: September 4, 2013
Last verified: September 2013
  Purpose

This phase II trial is studying the side effects and how well selumetinib works in treating patients with recurrent low-grade ovarian cancer. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Borderline Ovarian Surface Epithelial-stromal Tumor
Ovarian Serous Cystadenocarcinoma
Primary Peritoneal Cavity Cancer
Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor
Drug: selumetinib
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of AZD6244 (NSC #748727, IND #77782) in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary or Peritoneum

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Tumor response rate (complete and partial response) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: From study entry until disease progression, death or date of last contact, up to 10 years ] [ Designated as safety issue: No ]
    Progression free survival will be estimated and graphed using the Kaplan-Meier product-limit method.

  • Overall survival [ Time Frame: From entry into the study to death or the date of last contact, up to 10 years ] [ Designated as safety issue: No ]
    Overall survival will be estimated and graphed using the Kaplan-Meier product-limit method.

  • Frequency and severity of adverse effects assessed by Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 51
Study Start Date: December 2007
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (selumetinib)
Patients receive selumetinib PO twice a day on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: selumetinib
Given PO
Other Names:
  • ARRY-142886
  • AZD6244
Other: pharmacological study
Correlative studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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

II. To examine the acute toxicity of AZD6244 (NSC #748727) during the first course of treatment using CTCAE version 3.0.

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).

TERTIARY OBJECTIVES:

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

OUTLINE: This is a multicenter study.

Patients receive selumetinib orally (PO) twice a day on days 1-28. Courses 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 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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meeting 1 of the following diagnosis:

    • Low-grade ovarian carcinoma that recurred as low-grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas as defined by GOG, FIGO WHO, or S. G. Silverberg) or peritoneal carcinoma
    • Serous borderline ovarian carcinoma that recurred as low-grade serous carcinoma (invasive micropapillary serous carcinoma or invasive grade I serous carcinomas as defined by GOG, FIGO WHO, or S. G. Silverberg) or peritoneal carcinoma
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques including palpation, plain x-ray, CT scan, or MRI scan, OR ≥ 10 mm by spiral CT scan
  • Patients whose primary tumor was serous borderline ovarian carcinoma, low-grade serous ovarian carcinoma, 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)
  • No known brain metastases
  • GOG performance status 0-1
  • Platelet count ≥ 100,000/mm³
  • ANC count ≥ 1,500/mm³
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • Creatinine < 1.5 times ULN
  • Transaminases < 2.5 times ULN
  • Neuropathy ≤ grade 1
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for 4 weeks after completion of study therapy
  • QTc interval ≤ 450 msec and no factors that increase the risk of QT prolongation or arrhythmic events including, but not limited to, any of the following:

    • Heart failure
    • Hypokalemia
    • Family history of long QT interval syndrome
    • NYHA class III-IV heart failure
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD6244 or its excipient Captisol
  • No refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
  • No uncontrolled intercurrent illness including ongoing or active infection, psychiatric illness, or social situations that would limit compliance with study requirements
  • More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • No prior AZD6244
  • No prior MEK inhibitor
  • No HIV-positive patients on combination antiretroviral therapy
  • No concurrent medications with the potential to prolong the QT interval
  • No concurrent drugs known to affect or with the potential to affect selected CYP450 isoenzymes
  • No concurrent grapefruit or grapefruit juice during AZD6244 administration
  • No other concurrent investigational or commercial agents for this cancer
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00551070

  Hide Study Locations
Locations
United States, California
University of Southern California
Los Angeles, California, United States, 90033-0804
Stanford University Hospitals and Clinics
Stanford, California, United States, 94305
United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102
The Hospital of Central Connecticut
New Britain, Connecticut, United States, 06050
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
United States, Indiana
Saint Vincent Hospital and Health Services
Indianapolis, Indiana, United States, 46260
United States, Maine
Maine Medical Center-Bramhall Campus
Portland, Maine, United States, 04102
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, Michigan
Bronson Battle Creek
Battle Creek, Michigan, United States, 49017
Mecosta County Medical Center
Big Rapids, Michigan, United States, 49307
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, United States, 49503
Saint Mary's Health Care
Grand Rapids, Michigan, United States, 49503
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, United States, 49503
Holland Community Hospital
Holland, Michigan, United States, 49423
Mercy Health Partners-Mercy Campus
Muskegon, Michigan, United States, 49444
Mercy Health Partners-Hackley Campus
Muskegon, Michigan, United States, 49442
Munson Medical Center
Traverse City, Michigan, United States, 49684
Metro Health Hospital
Wyoming, Michigan, United States, 49519
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield
Springfield, Missouri, United States, 65802
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Gynecologic Oncology Network
Greenville, North Carolina, United States, 27834
United States, Ohio
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Mount Carmel Health Center West
Columbus, Ohio, United States, 43222
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
Miami Valley Hospital
Dayton, Ohio, United States, 45409
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Cancer Care Associates-Midtown
Tulsa, Oklahoma, United States, 74104
Cancer Care Associates-Yale
Tulsa, Oklahoma, United States, 74136-1929
United States, Pennsylvania
Abington Memorial Hospital
Abington, Pennsylvania, United States, 19001
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: John Farley Gynecologic Oncology Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00551070     History of Changes
Other Study ID Numbers: NCI-2009-00604, NCI-2009-00604, GOG-0239, CDR0000563965, GOG-0239, GOG-0239, U10CA027469
Study First Received: October 22, 2007
Last Updated: September 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystadenocarcinoma
Peritoneal Neoplasms
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Abdominal Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on April 17, 2014