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A Phase II Trial of AZD6244 (NSC #748727, IND #77782) in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary or Peritoneum


Phase 2
19 Years
N/A
Open (Enrolling)
Female
Borderline Ovarian Surface Epithelial-stromal Tumor, Ovarian Serous Cystadenocarcinoma, Primary Peritoneal Cavity Cancer, Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor

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Trial Information

A Phase II Trial of AZD6244 (NSC #748727, IND #77782) in Women With Recurrent Low-Grade Serous Carcinoma of the Ovary or Peritoneum


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tumor response rate (complete and partial response) assessed by Response Evaluation Criteria in Solid Tumors (RECIST)

Outcome Time Frame:

Up to 10 years

Safety Issue:

No

Principal Investigator

John Farley

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00604

NCT ID:

NCT00551070

Start Date:

December 2007

Completion Date:

Related Keywords:

  • Borderline Ovarian Surface Epithelial-stromal Tumor
  • Ovarian Serous Cystadenocarcinoma
  • Primary Peritoneal Cavity Cancer
  • Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor
  • Cystadenocarcinoma
  • Peritoneal Neoplasms
  • Cystadenocarcinoma, Serous
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Washington University School of MedicineSaint Louis, Missouri  63110
Abington Memorial HospitalAbington, Pennsylvania  19001
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Gynecologic Oncology NetworkGreenville, North Carolina  27858
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Hartford HospitalHartford, Connecticut  06102-5037
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
MetroHealth Medical CenterCleveland, Ohio  44109
Holland Community HospitalHolland, Michigan  49423
Munson Medical CenterTraverse City, Michigan  49684
Brigham and Women's HospitalBoston, Massachusetts  02115
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Mecosta County Medical CenterBig Rapids, Michigan  49307
Miami Valley HospitalDayton, Ohio  45409
Metro Health HospitalGrand Rapids, Michigan  49506
Riverside Methodist HospitalColumbus, Ohio  43214
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
M D Anderson Cancer CenterHouston, Texas  77030
University of Southern CaliforniaLos Angeles, California  90033
The Hospital of Central ConnecticutNew Britain, Connecticut  06050
Saint Vincent Hospital and Health ServicesIndianapolis, Indiana  46260
Grand Rapids Clinical Oncology ProgramGrand Rapids, Michigan  49503
Saint Mary's Health CareGrand Rapids, Michigan  49503
Spectrum Health at Butterworth CampusGrand Rapids, Michigan  49503
Mercy Health Partners-Mercy CampusMuskegon, Michigan  49443
Mercy Health Partners-Hackley CampusMuskegon, Michigan  49442
Ozark Health Ventures LLC dba Cancer Research for The Ozarks SpringfieldSpringfield, Missouri  65802
Mount Carmel Health Center WestColumbus, Ohio  43222
Cancer Care Associates-YaleTulsa, Oklahoma  74136-1929
Cancer Care Associates-MidtownTulsa, Oklahoma  74104
Maine Medical Center-Bramhall CampusPortland, Maine  04102
Stanford University Hospitals and ClinicsStanford, California  94305
Bronson Battle CreekBattle Creek, Michigan  49017