AZD6244 in Treating Woman With Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer - Full Text View

Sponsor:	Gynecologic Oncology Group
Collaborator:	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 Peritoneal Cavity Cancer	Drug: selumetinib Genetic: mutation analysis Genetic: protein expression analysis Other: immunohistochemistry staining method Other: pharmacological study	Phase II

Study Type:	Interventional
Study Design:	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:

MedlinePlus related topics: Cancer Ovarian Cancer

U.S. FDA Resources

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 or peritoneum 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. 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 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) 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

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 37 Study Locations

Sponsors and Collaborators

Gynecologic Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	John H. Farley, MD	Walter Reed Army Medical Center
Investigator:	David M. Gershenson, MD	M.D. Anderson Cancer Center

More Information

Additional Information:

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

No publications provided

Responsible Party:	Philip J. DiSaia, Gynecologic Oncology Group
ClinicalTrials.gov Identifier:	NCT00551070 History of Changes
Other Study ID Numbers:	CDR0000563965, GOG-0239
Study First Received:	October 22, 2007
Last Updated:	October 28, 2010
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
peritoneal cavity cancer

Additional relevant MeSH terms:

Ovarian Neoplasms
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female

Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases

ClinicalTrials.gov processed this record on February 09, 2012