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

NCT ID: NCT00939809

Last Updated: 2019-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Urokinase-Derived Peptide A6

Intervention Type: BIOLOGICAL

Given SC

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Urokinase-Derived Peptide A6

Given SC

Intervention Type: BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

A6; uPA-derived Peptide A6

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Gynecologic Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Gold

Role: PRINCIPAL_INVESTIGATOR

Gynecologic Oncology Group

Locations

Georgia Regents University Medical Center

Augusta, Georgia, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

Case Western Reserve University

Cleveland, Ohio, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, United States

Riverside Methodist Hospital

Columbus, Ohio, United States

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Women and Infants Hospital

Providence, Rhode Island, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

Countries

United States

Other Identifiers

NCI-2011-01927

Identifier Type: REGISTRY

Identifier Source: secondary_id

GOG-0170N

Identifier Type: -

Identifier Source: secondary_id

CDR0000644399

Identifier Type: -

Identifier Source: secondary_id

GOG-0170N

Identifier Type: OTHER

Identifier Source: secondary_id

GOG-0170N

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA027469

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GOG-0170N

Identifier Type: -

Identifier Source: org_study_id