Bortezomib 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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Phase II trial to study the effectiveness of bortezomib in treating patients who have persistent or recurrent ovarian epithelial cancer or primary peritoneal cancer. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the antitumor activity of bortezomib in patients with persistent or recurrent platinum-sensitive ovarian epithelial or primary peritoneal carcinoma. II. Determine the nature and degree of toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive bortezomib IV twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Official Title
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A Phase II Evaluation of Bortezomib (Velcade™, PS-341, NSC #681239, IND #58443) in the Treatment of Persistent or Recurrent Platinum-Sensitive Epithelial Ovarian or Primary Peritoneal Cancer

Conditions
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Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer

Intervention / Treatment
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* Drug: bortezomib
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed persistent or recurrent ovarian epithelial or primary peritoneal carcinoma Measurable disease At least 20 mm by conventional techniques (e.g., palpation, x-ray, plain CT scan, or MRI) OR at least 10 mm by spiral CT scan Must have had prior therapy with no more than 1 platinum-based chemotherapy regimen for primary disease (e.g., carboplatin, cisplatin, or other organoplatinum compound) A second regimen containing paclitaxel allowed provided patient received no prior paclitaxel therapy Platinum-sensitive disease Treatment-free interval without progressive disease for more than 6 months but less than 12 months after therapy with platinum-based regimen At least 1 target lesion outside previously irradiated field Ineligible for higher priority GOG protocol Performance status - GOG 0-2 (if received 1 prior therapy regimen) Performance status - GOG 0-1 (if received 2 prior therapy regimens) Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Creatinine no greater than 1.5 times ULN No evidence of acute ischemia or significant conduction abnormality (e.g., left anterior hemiblock in the presence of right bundle branch block or second or third degree atrioventricular block) on electrocardiogram No myocardial infarction within the past 6 months No cerebrovascular event or transient ischemic attack within the past 6 months Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection requiring antibiotics No other invasive malignancy within the past 5 years except non-melanoma skin cancer No sensory or motor neuropathy greater than grade 1 No more than 1 prior non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule inhibitors of signal transduction) for recurrent or persistent disease At least 4 weeks since prior biological or immunological agents and recovered No prior cytotoxic chemotherapy for recurrent or persistent disease, including retreatment with initial chemotherapy regimen At least 4 weeks since prior chemotherapy and recovered At least 1 week since prior anti-cancer hormonal therapy and recovered Concurrent hormone replacement therapy allowed At least 4 weeks since prior radiotherapy and recovered No prior radiotherapy to target lesions No prior radiotherapy to more than 25% of marrow-bearing areas At least 4 weeks since prior surgery and recovered No prior bortezomib No prior anti-cancer therapy that would preclude study treatment No concurrent amifostine or other protective agents
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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (bortezomib)<br>Patients receive bortezomib IV twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. | Drug: bortezomib<br>* Given IV<br>* Other names: VELCADE;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response Duration | 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. Complete and partial responses are included in the objective tumor response rate. | From study entry, up to 5 years | 
| Frequency and Severity of Observed Adverse Events |  | Up to 5 years | 
| Objective Partial/Complete Tumor Response Based on the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Number of participants who experienced an objective tumor response up to 5 years. Per RECIST version 1.0 criteria: each target lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or >= 10 mm when measured by spiral CT. Complete Response is a disappearance of all target and non-target lesions. Partial Response is 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. | From study entry until disease progression/intolerable toxicity/study withdrawal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | From study entry, up to 5 years following disease progression | 
| Progression-Free Survival | 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. | From study entry up to 5 years |