Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer
Conditions
Brief summary
Phase II trial to study the effectiveness of irofulven in treating patients who have recurrent or persistent ovarian epithelial cancer or primary peritoneal cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
Detailed description
OBJECTIVES: I. Determine the antitumor activity of irofulven in patients with persistent or recurrent platinum-sensitive ovarian epithelial or primary peritoneal cancer. II. Determine the toxicity of this drug in these patients. OUTLINE: Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression. Patients are followed at approximately 30 days, every 3 months for 2 years, and then every 6 months for 3 years. PROJECTED ACCRUAL: Approximately 22-60 patients will be accrued for this study within at least 6 months.
Interventions
DRUGirofulven
Given IV
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
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed ovarian epithelial or primary peritoneal carcinoma * Recurrent or persistent disease * At least 1 unidimensionally measurable target lesion\* defined as: * At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan * Must have received 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin, or another organoplatinum compound for primary disease * Initial treatment may have included high-dose, consolidation, or extended therapy administered after surgical or non-surgical assessment * Patients who have not received prior paclitaxel may receive a second regimen containing paclitaxel * Ineligible for a higher priority GOG protocol (e.g., any active phase III GOG protocol for the same patient population) * Platinum-sensitive disease * Platinum-free interval\*\* of more than 6 months, but less than 12 months duration, with no clinical evidence of progressive disease after response to platinum * Performance status - GOG 0-2 for patients who received 1 prior therapy regimen * Performance status - GOG 0-1 for patients who 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 normal * Creatinine clearance at least 60 mL/min * No prior congestive heart failure requiring medication * No uncontrolled hypertension within the past 6 months * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other invasive malignancies within the past 5 years except nonmelanoma skin cancer * No history of retinopathy and/or macular degeneration * No neuropathy (sensory and motor) greater than grade 1 * No active infection requiring antibiotics * No other illness or condition that would preclude study entry * No prior bone marrow or stem cell transplantation * At least 3 weeks since prior biologic therapy or immunotherapy for malignant tumor * One prior non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule signal transduction inhibitors) allowed * See Disease Characteristics * At least 3 weeks since prior chemotherapy and recovered * No prior irofulven * No additional prior cytotoxic chemotherapy for recurrent or persistent disease, including retreatment with initial chemotherapy regimens * At least 1 week since prior hormonal therapy for malignant tumor * Concurrent hormone replacement therapy allowed * See Disease Characteristics * At least 3 weeks since prior radiotherapy and recovered * No prior radiotherapy to more than 25% of marrow-bearing areas * Recovered from recent prior surgery * At least 3 weeks since any other prior therapy for malignant tumor * No prior anticancer treatment that would preclude study therapy * One prior noncytotoxic cytostatic regimen for recurrent or persistent disease allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | From entry into study until documented progression or death, assessed up to 5 years. | Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria: Complete Response is 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 dimensions; Increasing Disease is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Response is to be evaluated every 42 days for the first 6 months and every 6 months thereafter while the patient is receiving study treatment, then every 3 months for 2 years and every 6 months for the next 3 years until documented progression or death. |
| Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Assessed every cycle while on treatment, 30 days after the last cycle of treatment | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | From entry into study to death or date of last contact, assessed up to 5 years | Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria, progression is defined as at least a 20% increase in the sum of longest dimesions(LD) of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. |
Countries
United States
Participant flow
Recruitment details
Stage I of the study accrued patients from 6/2/2003 through 10/31/2005. Stage II of the study accrued patients from 1/3/2006 through 4/7/2008.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Irofulven) Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression. | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Incorrect cell type | 1 |
| Overall Study | Never treated | 4 |
| Overall Study | Platinum-sensitive interval >12 months | 1 |
Baseline characteristics
| Characteristic | Treatment (Irofulven) |
|---|---|
| Age, Continuous | 59.2 years STANDARD_DEVIATION 9.7 |
| Age, Customized 30-39 years | 1 participants |
| Age, Customized 40-49 years | 10 participants |
| Age, Customized 50-59 years | 17 participants |
| Age, Customized 60-69 years | 21 participants |
| Age, Customized 70-79 years | 4 participants |
| Age, Customized 80-89 years | 2 participants |
| Cell Type Endometrioid Adenocarcinoma | 2 participants |
| Cell Type Mixed Epithelial Carcinoma | 3 participants |
| Cell Type Serous Adenocarcinoma | 47 participants |
| Cell Type Undifferentiated Carcinoma | 3 participants |
| Recurrent/Persistent Disease | 55 participants |
| Region of Enrollment United States | 55 participants |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 55 / 55 |
| serious Total, serious adverse events | 18 / 55 |
Outcome results
Primary
Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Time frame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment
Population: Eligible and evaluable patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Neutropenia | 16 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Musculoskeletal | 2 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Constitutional | 4 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Metabolic | 2 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Thrombocytopenia | 11 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Neuropathy (sensory) | 1 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Gastrointestinal | 8 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Other neurologic | 2 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Other hematologic | 6 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Ocular | 4 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Infection | 4 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Pain | 1 participants |
| Treatment (Irofulven) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Leukopenia | 11 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Pain | 0 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Leukopenia | 0 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Thrombocytopenia | 2 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Neutropenia | 6 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Other hematologic | 0 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Constitutional | 0 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Gastrointestinal | 1 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Infection | 0 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Musculoskeletal | 0 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Metabolic | 1 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Neuropathy (sensory) | 0 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Other neurologic | 0 participants |
| Grade 4 (CTCAE v 2.0) | Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 | Ocular | 0 participants |
Primary
Tumor Response
Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria: Complete Response is 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 dimensions; Increasing Disease is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Response is to be evaluated every 42 days for the first 6 months and every 6 months thereafter while the patient is receiving study treatment, then every 3 months for 2 years and every 6 months for the next 3 years until documented progression or death.
Time frame: From entry into study until documented progression or death, assessed up to 5 years.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Irofulven) | Tumor Response | Partial Response | 7 participants |
| Treatment (Irofulven) | Tumor Response | Stable Disease | 30 participants |
| Treatment (Irofulven) | Tumor Response | Increase Disease | 12 participants |
| Treatment (Irofulven) | Tumor Response | Indeterminate | 6 participants |
Secondary
Progression-free Survival
Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria, progression is defined as at least a 20% increase in the sum of longest dimesions(LD) of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry.
Time frame: From entry into study to death or date of last contact, assessed up to 5 years
Population: Eligible and evaluable
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment (Irofulven) | Progression-free Survival | Median Overall Survival | 24.1 months |
| Treatment (Irofulven) | Progression-free Survival | Median Progression-free Survival | 6.7 months |