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

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ClinicalTrials.gov Identifier: NCT00551070
Recruitment Status : Active, not recruiting
First Posted : October 30, 2007
Results First Posted : June 29, 2015
Last Update Posted : April 30, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

October 22, 2007
October 30, 2007
June 10, 2015
June 29, 2015
April 30, 2018
December 17, 2007
July 23, 2013   (Final data collection date for primary outcome measure)
  • Tumor Response [ Time Frame: Every other cycle ]
    Complete and Partial Tumor Response by (Response Evaluation Criteria in Solid Tumors) RECIST 1.0
  • Adverse Events (Grade 3 or Higher) During First Cycle of Treatment [ Time Frame: Cycle 1 ]
  • Area Under the Curve (AUC) for AZD6244, 100 mg Administered Orally Twice Daily. [ Time Frame: 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. [ Time Frame: Pre-dose, and 1, 3, and 6 hours after administration of drug on Day 7 after the start of AZD6244 treatment ]
Tumor response rate (complete and partial response)
Complete list of historical versions of study NCT00551070 on ClinicalTrials.gov Archive Site
  • Progression-free Survival [ Time Frame: Every other cycle ]
  • Number of Courses Received [ Time Frame: Every cycle ]
  • Overall Survival [ Time Frame: 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 ]
  • Progression-free Survival
  • Overall survival
  • Toxicity as assessed by CTCAE version 3.0
  • Relationship of tumor response rate with DNA isolation and sequencing of BRAF and ras mutation analysis
  • Levels of BRAF and ras mutation in the tumor
  • Protein levels of p-ERK/ERKERK
  • Pharmacokinetic profile of AZD6244
Not Provided
Not Provided
 
Selumetinib Sulfate in Treating Woman With Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer
A Phase II Trial of AZD6244 (NSC# 748727) in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary or Peritoneum
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. Selumetinib sulfate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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 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 deoxyribonucleic acid (DNA) isolation with sequencing of b-raf proto-oncogene, serine/threonine kinase (braf), and retrovirus associated sequence (ras) mutation analysis and to explore their relationship with tumor response with AZD6244 (NSC #748727).

II. To examine protein levels of phosphorylated mitogen-activated protein kinase 1 (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. 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 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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Borderline Ovarian Epithelial Tumor
  • Low Grade Ovarian Serous Adenocarcinoma
  • Primary Peritoneal Carcinoma
  • Primary Peritoneal Low Grade Serous Adenocarcinoma
  • Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacological Study
    Correlative studies
  • Drug: Selumetinib Sulfate
    Given PO
    Other Names:
    • AZD-6244 Hydrogen Sulfate
    • AZD6244 Hydrogen Sulfate
    • AZD6244 Hydrogen Sulphate
    • Selumetinib Sulphate
Experimental: Treatment (selumetinib sulfate)
Patients receive selumetinib sulfate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
  • Drug: Selumetinib Sulfate
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
52
51
Not Provided
July 23, 2013   (Final data collection date for primary outcome measure)

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)
  • Measurable disease 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
  • 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
Sexes Eligible for Study: Female
19 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00551070
NCI-2009-00604
NCI-2009-00604 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000563965
GOG-0239 ( Other Identifier: NRG Oncology )
GOG-0239 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
U10CA027469 ( U.S. NIH Grant/Contract )
No
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: John Farley NRG Oncology
National Cancer Institute (NCI)
March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP