Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer
Conditions
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.
Interventions
DRUGbortezomib
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
OTHERpharmacological study
Correlative studies
Sponsors
Gynecologic Oncology Group
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Accrual was broken down into two cohorts. Cohort 1 enrolled 28 participants from 11/5/2001 through 1/6/2003. Cohort 2 enrolled 30 participants from 4/5/2004 through 9/6/2005.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Patients enrolled 11/5/2001 through 1/6/2003 receive bortezomib 1.5 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy. | 26 |
| Cohort 2 Patients enrolled 4/5/2004 through 9/6/2005 receive bortezomib 1.3 mg/m2/dose IV twice weekly for 2 weeks (Days 1,4,8, and 11) followed by a 10day rest period (Days 12-21). At least 72 hours should elapse between consecutive doses.Courses repeat every 3 weeks (21 days) until disease progression or adverse effects prohibit further therapy. | 29 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Never treated | 1 | 1 |
| Overall Study | Not platinum sensitive | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 11.1 | 55.8 years STANDARD_DEVIATION 11.4 | 57.2 years STANDARD_DEVIATION 11.2 |
| Age, Customized 20-29 years | 0 participants | 1 participants | 1 participants |
| Age, Customized 30-39 years | 1 participants | 1 participants | 2 participants |
| Age, Customized 40-49 years | 6 participants | 4 participants | 10 participants |
| Age, Customized 50-59 years | 8 participants | 10 participants | 18 participants |
| Age, Customized 60-69 years | 6 participants | 11 participants | 17 participants |
| Age, Customized 70-79 years | 5 participants | 1 participants | 6 participants |
| Age, Customized 80-89 years | 0 participants | 1 participants | 1 participants |
| Cell Type Adenocarcinoma, Unspecified | 1 participants | 0 participants | 1 participants |
| Cell Type Endometrioid Adenocarcinoma | 1 participants | 1 participants | 2 participants |
| Cell Type Mixed Epithelial Carcinoma | 2 participants | 1 participants | 3 participants |
| Cell Type Serous Adenocarcinoma | 21 participants | 25 participants | 46 participants |
| Cell Type Transitional Cell Carcinoma | 1 participants | 1 participants | 2 participants |
| Cell Type Undifferentiated Carcinoma | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Canada | 3 participants | 0 participants | 3 participants |
| Region of Enrollment United States | 23 participants | 29 participants | 52 participants |
| Sex: Female, Male Female | 26 Participants | 29 Participants | 55 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 26 | 29 / 29 |
| serious Total, serious adverse events | 5 / 26 | 6 / 29 |
Outcome results
Primary
Frequency and Severity of Observed Adverse Events
Time frame: Up to 5 years
Population: Eligible and evaluable patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Absolute neutrophil count (ANC) | 18 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Infection | 23 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Rash | 14 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Pain | 12 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Metabolic | 21 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Hepatic | 21 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Neuropathy (sensory) | 14 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Genitourinary/renal | 24 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Pulmonary | 21 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Platelets | 14 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Fatigue | 4 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Diarrhea | 13 Participants |
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Constipation | 17 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Genitourinary/renal | 1 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Platelets | 9 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Infection | 1 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Rash | 6 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Constipation | 4 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Diarrhea | 7 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Absolute neutrophil count (ANC) | 5 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Neuropathy (sensory) | 6 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Metabolic | 3 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pulmonary | 0 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Hepatic | 3 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Fatigue | 10 Participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pain | 8 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Neuropathy (sensory) | 3 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Constipation | 5 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Platelets | 0 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Pulmonary | 3 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Absolute neutrophil count (ANC) | 2 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Metabolic | 0 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Fatigue | 10 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Pain | 5 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Rash | 4 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Infection | 1 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Diarrhea | 2 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Genitourinary/renal | 0 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Hepatic | 1 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Metabolic | 2 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Fatigue | 1 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Absolute neutrophil count (ANC) | 1 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Genitourinary/renal | 1 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Pulmonary | 2 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Hepatic | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Constipation | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Diarrhea | 4 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Pain | 1 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Infection | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Rash | 2 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Neuropathy (sensory) | 3 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Platelets | 3 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Hepatic | 1 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Infection | 1 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Pulmonary | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Absolute neutrophil count (ANC) | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Fatigue | 1 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Pain | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Rash | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Diarrhea | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Neuropathy (sensory) | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Constipation | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Metabolic | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Genitourinary/renal | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 1 - Bortezomib 1.5 (mg/m2) | Frequency and Severity of Observed Adverse Events | Platelets | 0 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Diarrhea | 21 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Neuropathy (sensory) | 15 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Infection | 25 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Genitourinary/renal | 25 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Rash | 17 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Fatigue | 7 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pain | 15 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Hepatic | 22 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Absolute neutrophil count (ANC) | 21 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pulmonary | 26 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Platelets | 16 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Metabolic | 24 Participants |
| Grade 0 AEs Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Constipation | 11 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Diarrhea | 5 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Platelets | 10 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Absolute neutrophil count (ANC) | 5 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Fatigue | 11 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Rash | 9 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Constipation | 7 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Genitourinary/renal | 3 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Hepatic | 6 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Infection | 2 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Metabolic | 4 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Neuropathy (sensory) | 8 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pain | 5 Participants |
| Grade 1 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pulmonary | 0 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Genitourinary/renal | 1 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Diarrhea | 3 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pulmonary | 2 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Rash | 3 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Absolute neutrophil count (ANC) | 3 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Neuropathy (sensory) | 4 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Infection | 2 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Platelets | 3 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Metabolic | 1 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Hepatic | 1 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pain | 7 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Constipation | 9 Participants |
| Grade 2 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Fatigue | 6 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Infection | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Genitourinary/renal | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Constipation | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Metabolic | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Diarrhea | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pulmonary | 1 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Neuropathy (sensory) | 2 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Rash | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Fatigue | 5 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pain | 2 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Absolute neutrophil count (ANC) | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Hepatic | 0 Participants |
| Grade 3 AEs (CTCAE v 2.0) Cohort 2 - Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Platelets | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Absolute neutrophil count (ANC) | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pulmonary | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Metabolic | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Genitourinary/renal | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Pain | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Infection | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Constipation | 2 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Neuropathy (sensory) | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Platelets | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Rash | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Fatigue | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Hepatic | 0 Participants |
| Grade 4 AEs (CTCAE v 2.0) Cohort 2- Bortezomib (1.3 mg/m2) | Frequency and Severity of Observed Adverse Events | Diarrhea | 0 Participants |
Primary
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.
Time frame: From study entry until disease progression/intolerable toxicity/study withdrawal
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Objective Partial/Complete Tumor Response Based on the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | 1 participants |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Objective Partial/Complete Tumor Response Based on the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | 2 participants |
Primary
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.
Time frame: From study entry, up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Tumor Response Duration | 3.9 months |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Tumor Response Duration | 24.1 months |
Secondary
Overall Survival
Time frame: From study entry, up to 5 years following disease progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Overall Survival | 18.2 months |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Overall Survival | 27.2 months |
Secondary
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.
Time frame: From study entry up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 - Bortezomib 1.5 (mg/m2) | Progression-Free Survival | 1.5 months |
| Cohort 2 - Bortezomib (1.3 mg/m2) | Progression-Free Survival | 1.4 months |