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

Study Overview
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Brief Summary
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RATIONALE: Enzastaurin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well enzastaurin works in treating patients with persistent or recurrent ovarian epithelial cancer or primary peritoneal cancer.

Detailed Description
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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.

Official Title
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A Phase II Evaluation of Enzastaurin (Lilly IND # 60, 933) in the Treatment of Persistent or Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma

Conditions
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Ovarian Cancer, Primary Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: enzastaurin hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: enzastaurin hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 | RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. | CT scan or MRI if used to follow lesions for measurable disease every other cycle for the first 6 months; every 6 months thereafter until disease progression for up to 5 years. | 
| Progression-free Survival > 6 Months Using RECIST 1.0 | Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. | CT scan or MRI if used to follow lesion for measurable disease every other cycle for first 6 months; every 6 months thereafter until disease progression for up to 5 years. | 
| Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Number of participants with a maximum grade of 3 or higher during the treatment period. | Assessed every cycle while on treatment, 30 days after the last cycle of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration Overall Survival | Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. | 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. | 
| Duration of Progression-free Survival (PFS) | Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. | CT scan or MRI if used to follow lesion for measurable disease every other cycle for first 6 months; every 6 months thereafter until disease progression for up to 5 years. | 
| Prognostic Factor - Number of Patients With Platinum Sensitivity | Platinum sensitive = a platinum-free interval between 6 and 12 months. | Baseline | 
| Prognostic Factor - Initial Performance Status | Performance status 0 = Fully active, able to carry on all pre-disease performance without restriction Performance status 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, e.g., light housework, office work | Baseline | 
| Prognostic Factor - Age at Study Entry |  | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian epithelial cancer, primary peritoneal cavity cancer