A6 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

Phase 2

Completed

Conditions: Undifferentiated Ovarian Carcinoma
Ovarian Brenner Tumor
Ovarian Serous Cystadenocarcinoma
Primary Peritoneal Carcinoma
Recurrent Ovarian Carcinoma
Ovarian Clear Cell Cystadenocarcinoma
Fallopian Tube Carcinoma
Malignant Ovarian Mixed Epithelial Tumor
Ovarian Endometrioid Adenocarcinoma
Ovarian Mucinous Cystadenocarcinoma

Interventions: Biological: Urokinase-Derived Peptide A6
Other: Laboratory Biomarker Analysis

Registration Number: NCT00939809

Lead Sponsor: Gynecologic Oncology Group

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 31

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (urokinase-derived peptide A6)	Laboratory Biomarker Analysis	Patients receive A6 subcutaneously once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Treatment (urokinase-derived peptide A6)	Urokinase-Derived Peptide A6	Patients receive A6 subcutaneously once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
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)
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.

Secondary Outcome Measures

Name	Time	Method
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.
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.

Trial Locations

Locations (16): Georgia Regents University Medical Center
🇺🇸
Augusta, Georgia, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
Stony Brook University Medical Center
🇺🇸
Stony Brook, New York, United States
Riverside Methodist Hospital
🇺🇸
Columbus, Ohio, United States
Hillcrest Hospital Cancer Center
🇺🇸
Mayfield Heights, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
Magee-Womens Hospital of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Women and Infants Hospital
🇺🇸
Providence, Rhode Island, United States
Huntsman Cancer Institute/University of Utah
🇺🇸
Salt Lake City, Utah, United States
Gundersen Lutheran Medical Center
🇺🇸
La Crosse, Wisconsin, United States
Nebraska Methodist Hospital
🇺🇸
Omaha, Nebraska, United States
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸
Cleveland, Ohio, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States