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AZD6244 in Treating Woman With Recurrent Low-Grade Ovarian Cancer
This study has been suspended.
Sponsors and Collaborators: Gynecologic Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00551070
  Purpose

RATIONALE: AZD6244 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects and how well AZD6244 works in treating patients with recurrent low-grade ovarian cancer.


Condition Intervention Phase
Ovarian Cancer
Drug: MEK inhibitor AZD6244
Procedure: immunohistochemistry staining method
Procedure: mutation analysis
Procedure: pharmacological study
Procedure: protein expression analysis
Phase II

MedlinePlus related topics: Cancer Ovarian Cancer
Drug Information available for: ARRY 142886
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Trial of AZD6244 (NSC #741078, IND #77782) in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary

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

Primary Outcome Measures:
  • Tumor response rate (complete and partial response) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Toxicity as assessed by CTCAE version 3.0 [ Designated as safety issue: Yes ]
  • Relationship of tumor response rate with DNA isolation and sequencing of BRAF and ras mutation analysis [ Designated as safety issue: No ]
  • Levels of BRAF and ras mutation in the tumor [ Designated as safety issue: No ]
  • Protein levels of p-ERK/ERKERK [ Designated as safety issue: No ]
  • Pharmacokinetic profile of AZD6244 [ Designated as safety issue: No ]

Estimated Enrollment: 51
Study Start Date: December 2007
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To examine the tumor response rate in patients with recurrent low-grade serous ovarian cancer treated with AZD6244.
  • To examine the acute toxicity of this drug during the first course of treatment.
  • To examine DNA isolation with sequencing of BRAF and ras mutation analysis and to explore their relationship with tumor response in patients treated with this drug.

Secondary

  • To examine the toxicity of this drug using the 21 major categories of the CTCAE version 3.0.
  • To examine the dose and number of courses of AZD6244 given.
  • To estimate the progression-free survival and overall survival of patients treated with this drug.
  • To examine protein levels of p-ERK/ERKERK and explore their relationship with tumor response in patients treated with this drug.
  • To define the pharmacokinetic profile of AZD6244.

OUTLINE: This is a multicenter study.

Patients receive oral AZD6244 twice a day on days 1-28 in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for correlative and pharmacokinetic studies and to analyze AZD6244 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

DISEASE CHARACTERISTICS:

  • 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)
    • 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)
  • 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 or low-grade serous ovarian 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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

  Show 35 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Study Chair: John H. Farley, MD Walter Reed Army Medical Center
Investigator: David M. Gershenson, MD M.D. Anderson Cancer Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000563965, GOG-0239
Study First Received: October 22, 2007
Last Updated: November 25, 2008
ClinicalTrials.gov Identifier: NCT00551070  
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
borderline ovarian surface epithelial-stromal tumor
ovarian serous cystadenocarcinoma
recurrent borderline ovarian surface epithelial-stromal tumor

Study placed in the following topic categories:
Cystadenocarcinoma, Serous
Ovarian cancer
Ovarian Neoplasms
Gonadal Disorders
Genital Neoplasms, Female
Endocrine System Diseases
Urogenital Neoplasms
Ovarian Diseases
Ovarian epithelial cancer
Recurrence
Carcinoma
Genital Diseases, Female
Endocrinopathy
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Adnexal Diseases

ClinicalTrials.gov processed this record on January 15, 2009