Fallopian Tube Carcinoma, Malignant Ovarian Mixed Epithelial Tumor, Ovarian Brenner Tumor, Ovarian Clear Cell Cystadenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mucinous Cystadenocarcinoma, Ovarian Serous Cystadenocarcinoma, Primary Peritoneal Carcinoma, Recurrent Ovarian Carcinoma, Undifferentiated Ovarian Carcinoma
Conditions
Brief summary
This phase II trial is studying the side effects and how well A6 works in treating patients with persistent or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. A6 may stop the growth of tumor cells by blocking blood flow to the tumor.
Detailed description
PRIMARY OBJECTIVES: I. To assess the activity of A6, as measured by the 6-month progression-free survival (PFS) rate and objective tumor response (complete or partial) rate, in patients with persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal carcinoma. II. To determine the frequency and severity of adverse events as assessed by CTCAE v3.0. SECONDARY OBJECTIVES: I. To characterize the duration of PFS and overall survival. II. To identify biomarkers of drug effect on peripheral blood mononuclear cells (PBMCs). TERTIARY OBJECTIVES: I. To explore whether genes identified as being up- or down-regulated by exposure of human PBMCs to A6 in vitro are also up- or down-regulated following treatment of patients with A6 in vivo. II. To explore whether there is an association between the expression of candidate A6 receptors in the tumor prior to treatment with A6 (as determined by IHC) and response and PFS. III. To explore whether there is an association between change in expression of candidate biomarkers in PBMCs between 0-24 hours following the first dose of A6 and response and PFS. IV. To explore whether there is an association between change in expression of candidate biomarkers in PBMCs over the course of the first one month cycle (course 1) and response and PFS. V. To determine whether there is an association between plasma A6 levels measured on days 2 (24 hours after the first dose and 4 hours after the second dose) and 8 (prior to injection of A6) of course 1 and levels of expression of candidate biomarkers in PBMCs collected on the same days. VI. To explore whether there is an association between plasma A6 levels measured on days 2 (24 hours after the first dose and 4 hours after the second dose) and 8 (prior to injection of A6) of course 1 and response and PFS. VII. To explore whether there is an association between candidate serum biomarkers and response and PFS over the course of A6 treatment. OUTLINE: This is a multicenter study. Patients receive A6 subcutaneously 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.
Interventions
BIOLOGICALUrokinase-Derived Peptide A6
Given SC
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Gynecologic Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal carcinoma, including any of the following epithelial cell types: * Serous adenocarcinoma * Endometrioid adenocarcinoma * Mucinous adenocarcinoma * Undifferentiated carcinoma * Clear cell adenocarcinoma * Mixed epithelial carcinoma * Transitional cell carcinoma * Malignant Brenner tumor * Adenocarcinoma not otherwise specified * Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan * Must have ≥ 1 target lesion to assess response as defined by RECIST criteria * Tumors within a previously irradiated field are designated as non-target lesions unless progression is documented or a biopsy is obtained to confirm persistence of disease ≥ 90 days following completion of radiotherapy * Must not be eligible for a higher priority GOG clinical trial, if one exists (i.e., any active GOG Phase III clinical trial for the same patient population) * Must have received 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin, or another organoplatinum compound for management of primary disease * Initial treatment may have included high-dose therapy, consolidation therapy, non-cytotoxic therapy, or extended therapy administered after surgical or non-surgical assessment * One additional cytotoxic regimen for management of recurrent or persistent disease allowed * Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease) must have a platinum-free interval of \< 12 months, have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy * GOG performance status 0-2 (for patients who received 1 prior regimen) OR 0-1 (for patients who received 2 prior regimens) * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Creatinine ≤ 1.5 times upper limit of normal (ULN) * Bilirubin ≤ 1.5 times ULN * SGOT ≤ 2.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able and willing to self-administer daily subcutaneous (SC) injections or has a caregiver who is willing and able to administer daily SC injections * No active infection requiring antibiotics, except uncomplicated urinary tract infection * No neuropathy (sensory and motor) \> grade 2, according to CTCAE v3.0 * No other invasive malignancies within the past 5 years, except for non-melanoma skin cancer * No history of sensitivity to A6 * No active gastrointestinal bleeding within the past month * No other disease that, in the opinion of the investigator, could jeopardize patient safety or interfere with study objectives * No concurrent amifostine or other protective reagents * Recovered from prior surgery, radiotherapy, or chemotherapy * No prior non-cytotoxic therapy for management of recurrent or persistent disease * Prior biologic (non-cytotoxic) therapy as part of primary treatment regimen allowed * At least 1 week since prior hormonal therapy directed at the malignant tumor * At least 3 weeks since any other prior therapy directed at the malignant tumor, including immunological agents * More than 2 weeks since prior major surgical procedure * More than 5 years since prior radiotherapy to any portion of the abdominal cavity or pelvis other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer * More than 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin AND remains free of recurrent or metastatic disease * Patients with ductal breast carcinoma in situ may have undergone localized radiotherapy within the past 3 years * More than 5 years since prior chemotherapy for any abdominal or pelvic tumor other than for the treatment of ovarian, fallopian tube, or primary peritoneal cancer * More than 3 years since prior adjuvant chemotherapy for localized breast cancer AND remains free of recurrent or metastatic disease * More than 30 days since prior investigational drugs * No prior A6 * No prior radiotherapy to \> 25% of marrow-bearing areas * No prior cancer treatment that would contraindicate study therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival at 6 Months | Scans to assess progression were done every other cycle for the first 6 months. | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response. |
| Tumor Response | Scans to assess response were done every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. | Complete and Partial Tumor Response by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Per RECIST v1.0 for target lesions and assessed by MRI or CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response. |
| Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Every cycle during treatment (average collection time = 4 months) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | scans to assess response were done every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response. |
| Overall Survival | Every other cycle, up to 5 years | — |
| Biomarkers of Drug Effect on Peripheral Blood Mononuclear Cells (PBMCs) | Day 1 prior to dosing; Day 2 prior to dosing and 4-hour post dosing; Day 8 prior to dosing. | Note: due to the limited activity of this agent, it was decided not to expend resources assaying the PBMCs. Data was not collected. |
Countries
United States
Participant flow
Recruitment details
The study was activated on 7/6/2009 and closed to accrual on 1/4/2010.
Participants by arm
| Arm | Count |
|---|---|
| A6 (Subcutaneous) 300 mg A6 Subcutaneously daily (2 injections of 150 mg) (cycle = 28 days) until disease progression or adverse effects prohibit further therapy | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | A6 (Subcutaneous) |
|---|---|
| Age, Customized 40-49 years | 1 participants |
| Age, Customized 50-59 years | 11 participants |
| Age, Customized 60-69 years | 17 participants |
| Age, Customized 70-79 years | 2 participants |
| Sex: Female, Male Female | 31 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 | 29 / 31 |
| serious Total, serious adverse events | 9 / 31 |
Outcome results
Primary
Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Time frame: Every cycle during treatment (average collection time = 4 months)
Population: Eligible and Treated Patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A6 (Subcutaneous) | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Constitutional | 2 Participants |
| A6 (Subcutaneous) | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Gastrointestinal | 1 Participants |
| A6 (Subcutaneous) | Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Hemorrhage | 1 Participants |
Primary
Progression-free Survival at 6 Months
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response.
Time frame: Scans to assess progression were done every other cycle for the first 6 months.
Population: Eligible and treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A6 (Subcutaneous) | Progression-free Survival at 6 Months | 6.5 percentage of participants |
Primary
Tumor Response
Complete and Partial Tumor Response by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Per RECIST v1.0 for target lesions and assessed by MRI or CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response.
Time frame: Scans to assess response were done every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels.
Population: Eligible and treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A6 (Subcutaneous) | Tumor Response | 0 percentage of participants |
Secondary
Biomarkers of Drug Effect on Peripheral Blood Mononuclear Cells (PBMCs)
Note: due to the limited activity of this agent, it was decided not to expend resources assaying the PBMCs. Data was not collected.
Time frame: Day 1 prior to dosing; Day 2 prior to dosing and 4-hour post dosing; Day 8 prior to dosing.
Population: due to the limited activity of this agent, it was decided not to expend resources assaying the PBMCs.
Secondary
Overall Survival
Time frame: Every other cycle, up to 5 years
Population: Eligible and treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A6 (Subcutaneous) | Overall Survival | 10.6 months |
Secondary
Progression-free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response.
Time frame: scans to assess response were done every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels.
Population: Eligible and treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A6 (Subcutaneous) | Progression-free Survival | 2.0 months |