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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)

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. Selumetinib sulfate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
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 Other: Pharmacological Study Drug: Selumetinib Sulfate Phase 2

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of AZD6244 (NSC# 748727) in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary or Peritoneum
Actual Study Start Date : December 17, 2007
Actual Primary Completion Date : July 23, 2013


Arm Intervention/treatment
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.
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



Primary Outcome Measures :
  1. Tumor Response [ Time Frame: Every other cycle ]
    Complete and Partial Tumor Response by (Response Evaluation Criteria in Solid Tumors) RECIST 1.0

  2. Adverse Events (Grade 3 or Higher) During First Cycle of Treatment [ Time Frame: Cycle 1 ]
  3. 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 ]
  4. 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 ]

Secondary Outcome Measures :
  1. Progression-free Survival [ Time Frame: Every other cycle ]
  2. Number of Courses Received [ Time Frame: Every cycle ]
  3. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00551070


  Show 49 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: John Farley NRG Oncology

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 ( 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 )
First Posted: October 30, 2007    Key Record Dates
Results First Posted: June 29, 2015
Last Update Posted: April 30, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
Carcinoma
Adenocarcinoma
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous