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

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