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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression-free Survival at 6 Months
Secondary Outcome
Progression-free Survival
Condition
Fallopian Tube Carcinoma
Intervention
Urokinase-Derived Peptide A6
Study Arms / Comparison Groups
Treatment (urokinase-derived peptide A6)
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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
31
Start Date
July 2009
Primary Completion Date
July 2012
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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Michael Gold, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00939809
Organization ID
GOG-0170N
Secondary IDs
NCI-2011-01927
Responsible Party
Sponsor
Study Sponsor
Gynecologic Oncology Group
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Michael Gold, Principal Investigator, Gynecologic Oncology Group
Verification Date
February 2015