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

G

Gynecologic Oncology Group (GOG)

Status and phase

Completed
Phase 2

Conditions

Primary Peritoneal Carcinoma
Ovarian Serous Cystadenocarcinoma
Recurrent Ovarian Carcinoma
Undifferentiated Ovarian Carcinoma
Ovarian Mucinous Cystadenocarcinoma
Ovarian Brenner Tumor
Malignant Ovarian Mixed Epithelial Tumor
Ovarian Clear Cell Cystadenocarcinoma
Fallopian Tube Carcinoma
Ovarian Endometrioid Adenocarcinoma

Treatments

Biological: Urokinase-Derived Peptide A6
Other: Laboratory Biomarker Analysis

Study type

Interventional

Funder types

NETWORK
NIH

Identifiers

NCT00939809
U10CA027469 (U.S. NIH Grant/Contract)
NCI-2011-01927 (Registry Identifier)
CDR0000644399
GOG-0170N

Details and patient eligibility

About

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.

Full 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.

Enrollment

31 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

31 participants in 1 patient group

Treatment (urokinase-derived peptide A6)
Experimental group
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.
Treatment:
Other: Laboratory Biomarker Analysis
Biological: Urokinase-Derived Peptide A6

Trial contacts and locations

16

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Data sourced from clinicaltrials.gov

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