Enzastaurin in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer or Primary Peritoneal Cancer

OBJECTIVES:

Primary

- Assess the efficacy of enzastaurin hydrochloride, in terms of 6-month progression-free
survival or objective tumor response, in patients with recurrent or persistent ovarian
epithelial or primary peritoneal cancer.

- Determine the nature and degree of toxicity of this regimen in these patients.

Secondary

- Determine the duration of progression-free and overall survival of patients treated with
this regimen.

- Determine the effects of prognostic variables, including platinum sensitivity, initial
performance status, and age, in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral enzastaurin hydrochloride 3 times on day 1 and then once daily on days
2-28 of course 1. For all subsequent courses, patients receive enzastaurin hydrochloride once
daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 68 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed ovarian epithelial or primary peritoneal carcinoma

- Recurrent or persistent disease

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- Must have ≥ 1 target lesion to assess response

- Tumors within a previously irradiated field are designated as "nontarget"
lesions unless progression is documented or a biopsy is obtained to confirm
persistence ≥ 90 days after completion of radiotherapy

- Must have received 1 prior platinum-based chemotherapy regimen containing carboplatin,
cisplatin, or another organoplatinum compound for management of primary disease

- Initial treatment may have included high-dose therapy, consolidation therapy, or
extended therapy administered after surgical or nonsurgical assessment

- Must meet any 1 of the following criteria for platinum-based therapy:

- Disease progression during therapy

- Treatment-free interval after completion of treatment < 12 months

- Disease persistence after completion of therapy

- Ineligible for a higher priority GOG clinical trial

PATIENT CHARACTERISTICS:

- GOG performance status 0-1 (for patients who received 2 prior treatment regimens) OR
0-2 (for patients who received 1 prior treatment regimen)

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL (transfusions allowed)

- Creatinine < 1.5 times upper limit of normal (ULN)

- Bilirubin ≤ 2 times ULN

- Alkaline phosphatase ≤ 3 times ULN (5 times ULN if liver metastases are present)

- AST and ALT ≤ 3 times ULN (5 times ULN if liver metastases are present)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- Able to swallow tablets

- No sensory or motor neuropathy > grade 1

- No active infection requiring antibiotics

- No other invasive malignancies or evidence of cancer within the past 5 years except
nonmelanoma skin cancer

- No serious systemic disorders that would preclude study compliance, including an
abnormal ECG indicative of cardiac disease

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior surgery, radiotherapy, or chemotherapy

- At least 1 week since prior anticancer hormonal therapy

- No more than 1 additional cytotoxic regimen for management of recurrent or persistent
disease

- At least 4 weeks since other prior anticancer therapy, including immunotherapy

- At least 30 days since prior investigational drugs

- No prior enzastaurin hydrochloride

- No prior radiotherapy to > 25% of marrow-bearing areas

- No prior noncytotoxic therapy, including bevacizumab, for recurrent or persistent
disease

- No prior treatment that would preclude treatment on this protocol

- No concurrent chemotherapy, immunotherapy, or other experimental medications

- No concurrent enzyme-inducing antiepileptic drugs, including carbamazepine,
phenobarbital, or phenytoin

- No other concurrent systemic anticancer therapy

- No concurrent radiotherapy, including palliative radiotherapy

- No concurrent agents that stimulate thrombopoiesis

- No concurrent amifostine or other protective reagents

- Concurrent hormone replacement therapy allowed

- Concurrent bisphosphonates allowed provided bony metastases are present