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

Primary Purpose

Fallopian Tube Carcinoma, Malignant Ovarian Mixed Epithelial Tumor, Ovarian Brenner Tumor

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Urokinase-Derived Peptide A6
Laboratory Biomarker Analysis
Sponsored by
Gynecologic Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fallopian Tube Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Georgia Regents University Medical Center
  • University of Iowa Hospitals and Clinics
  • Nebraska Methodist Hospital
  • Stony Brook University Medical Center
  • Case Western Reserve University
  • MetroHealth Medical Center
  • Cleveland Clinic Cancer Center/Fairview Hospital
  • Riverside Methodist Hospital
  • Hillcrest Hospital Cancer Center
  • University of Oklahoma Health Sciences Center
  • Abington Memorial Hospital
  • Magee-Womens Hospital of UPMC
  • Women and Infants Hospital
  • Vanderbilt-Ingram Cancer Center
  • Huntsman Cancer Institute/University of Utah
  • Gundersen Lutheran Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (urokinase-derived peptide A6)

Arm Description

Patients receive A6 subcutaneously once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

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.
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.
Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0

Secondary Outcome Measures

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.
Overall Survival
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.

Full Information

First Posted
July 14, 2009
Last Updated
January 2, 2019
Sponsor
Gynecologic Oncology Group
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00939809
Brief Title
A6 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
Official Title
A Phase II Evaluation of a Urokinase-Derived Peptide (A6) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gynecologic Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (urokinase-derived peptide A6)
Arm Type
Experimental
Arm Description
Patients receive A6 subcutaneously once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
Urokinase-Derived Peptide A6
Other Intervention Name(s)
A6, uPA-derived Peptide A6
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Progression-free Survival at 6 Months
Description
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.
Title
Tumor Response
Description
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.
Title
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)
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
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.
Title
Overall Survival
Time Frame
Every other cycle, up to 5 years
Title
Biomarkers of Drug Effect on Peripheral Blood Mononuclear Cells (PBMCs)
Description
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.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Gold
Organizational Affiliation
Gynecologic Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgia Regents University Medical Center
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Nebraska Methodist Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Stony Brook University Medical Center
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
MetroHealth Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Cleveland Clinic Cancer Center/Fairview Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44111
Country
United States
Facility Name
Riverside Methodist Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43214
Country
United States
Facility Name
Hillcrest Hospital Cancer Center
City
Mayfield Heights
State/Province
Ohio
ZIP/Postal Code
44124
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Abington Memorial Hospital
City
Abington
State/Province
Pennsylvania
ZIP/Postal Code
19001
Country
United States
Facility Name
Magee-Womens Hospital of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Women and Infants Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Huntsman Cancer Institute/University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Gundersen Lutheran Medical Center
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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