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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: June 17, 2014
Last verified: June 2014

July 14, 2009
June 17, 2014
August 2009
July 2012   (final data collection date for primary outcome measure)
  • 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 ]
  • Frequency and severity of adverse events as assessed by CTCAE v3.0 [ Designated as safety issue: Yes ]
  • 6-month progression-free survival rate [ Designated as safety issue: No ]
  • Objective tumor response (complete or partial) rate [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00939809 on ClinicalTrials.gov Archive Site
  • 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.
Duration of progression-free survival and overall survival [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A6 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
A Phase II Evaluation of a Urokinase-Derived Peptide (A6) (IND #64,298) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

RATIONALE: A6 may stop the growth of tumor cells by blocking blood flow to the tumor.

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.

OBJECTIVES:

Primary

  • 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.
  • To determine the frequency and severity of adverse events as assessed by CTCAE v3.0.

Secondary

  • To characterize the duration of PFS and overall survival.
  • To identify biomarkers of drug effect on peripheral blood mononuclear cells (PBMCs).

Tertiary

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Interventional
Phase 2
Masking: Open Label
Primary Purpose: Treatment
  • Fallopian Tube Cancer
  • Ovarian Cancer
  • Primary Peritoneal Cavity Cancer
  • Biological: urokinase-derived peptide A6
  • Other: laboratory biomarker analysis
Not Provided
Gold MA, Brady WE, Lankes HA, Rose PG, Kelley JL, De Geest K, Crispens MA, Resnick KE, Howell SB. A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2012 Jun;125(3):635-9. doi: 10.1016/j.ygyno.2012.03.023. Epub 2012 Mar 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
31
Not Provided
July 2012   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • 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
  • No concurrent amifostine or other protective reagents
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00939809
GOG-0170N, CDR0000644399, NCI-2011-01927
Yes
Gynecologic Oncology Group
Gynecologic Oncology Group
National Cancer Institute (NCI)
Study Chair: Michael A. Gold, MD Vanderbilt Medical Group & Clinic at Vanderbilt Medical Center
Gynecologic Oncology Group
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP