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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT00939809
First received: July 14, 2009
Last updated: February 27, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention Phase
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
Biological: Urokinase-Derived Peptide A6
Other: Laboratory Biomarker Analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Progression-free Survival at 6 Months [ Time Frame: Scans to assess progression were done every other cycle for the first 6 months. ] [ Designated as safety issue: No ]

    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 [ 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. ] [ Designated as safety issue: No ]

    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.


  • Frequency and Severity of Adverse Events as Assessed by CTCAE v3.0 [ Time Frame: Every cycle during treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free Survival [ 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. ] [ Designated as safety issue: No ]

    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 [ Time Frame: Every other cycle, up to 5 years ] [ Designated as safety issue: No ]
  • Biomarkers of Drug Effect on Peripheral Blood Mononuclear Cells (PBMCs) [ Time Frame: Day 1 prior to dosing; Day 2 prior to dosing and 4-hour post dosing; Day 8 prior to dosing. ] [ Designated as safety issue: No ]
    Note: due to the limited activity of this agent, it was decided not to expend resources assaying the PBMCs.


Enrollment: 31
Study Start Date: July 2009
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (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.
Biological: Urokinase-Derived Peptide A6
Given SC
Other Names:
  • A6
  • uPA-derived Peptide A6
Other: Laboratory Biomarker Analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00939809

Locations
United States, Georgia
Georgia Regents University Medical Center
Augusta, Georgia, United States, 30912
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
United States, New York
Stony Brook University Medical Center
Stony Brook, New York, United States, 11794
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, United States, 44111
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
Riverside Methodist Hospital
Columbus, Ohio, United States, 43214
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, United States, 44124
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Abington Memorial Hospital
Abington, Pennsylvania, United States, 19001
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Women and Infants Hospital
Providence, Rhode Island, United States, 02905
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Utah
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States, 84112
United States, Wisconsin
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States, 54601
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Principal Investigator: Michael Gold Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT00939809     History of Changes
Other Study ID Numbers: GOG-0170N, NCI-2011-01927, GOG-0170N, CDR0000644399, GOG-0170N, GOG-0170N, U10CA027469
Study First Received: July 14, 2009
Results First Received: February 3, 2014
Last Updated: February 27, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Brenner Tumor
Carcinoma
Carcinoma, Endometrioid
Cystadenocarcinoma
Cystadenocarcinoma, Mucinous
Cystadenocarcinoma, Serous
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Endometrial Neoplasms
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Cystic, Mucinous, and Serous
Neoplasms, Fibroepithelial
Neoplasms, Fibrous Tissue
Ovarian Diseases
Urogenital Neoplasms
Uterine Neoplasms

ClinicalTrials.gov processed this record on August 03, 2015