Clinical trial NCT00939809: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: GOG Foundation
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-07-15
Enrollment: 31
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free Survival at 6 Months
timeFrame: Scans to assess progression were done every other cycle for the first 6 months.
measure: Tumor Response
timeFrame: 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.
measure: Incidence of Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
timeFrame: Every cycle during treatment (average collection time = 4 months)
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 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.
measure: Overall Survival
timeFrame: Every other cycle, up to 5 years
measure: Biomarkers of Drug Effect on Peripheral Blood Mononuclear Cells (PBMCs)
timeFrame: Day 1 prior to dosing; Day 2 prior to dosing and 4-hour post dosing; Day 8 prior to dosing.
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Georgia Regents University Medical Center
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center/Fairview Hospital
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
Study officials:
affiliation: Gynecologic Oncology Group
name: Michael Gold
role: PRINCIPAL_INVESTIGATOR
References: