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

Phase 2

Completed

Conditions: Recurrent Ovarian Epithelial Cancer
Primary Peritoneal Cavity Cancer

Interventions: Drug: bortezomib
Other: laboratory biomarker analysis
Other: pharmacological study

Registration Number: NCT00023712

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 58

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (bortezomib)	laboratory biomarker analysis	Patients receive bortezomib IV twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment (bortezomib)	pharmacological study	Patients receive bortezomib IV twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Treatment (bortezomib)	bortezomib	Patients receive bortezomib IV twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Tumor Response Duration	From study entry, up to 5 years	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.
Objective Partial/Complete Tumor Response Based on the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) Criteria	From study entry until disease progression/intolerable toxicity/study withdrawal	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.
Frequency and Severity of Observed Adverse Events	Up to 5 years

Secondary Outcome Measures

Name	Time	Method
Overall Survival	From study entry, up to 5 years following disease progression
Progression-Free Survival	From study entry up to 5 years	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.