Phase II Study of Clinical Activity of Pegaspargase in Women With Relapsed or Refractory Epithelial Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer
- The bacterial enzyme L-asparaginase (L-ASP) catalyzes hydrolysis of asparagine to
aspartate and is used to treat acute lymphoblastic leukemia (ALL).Studies demonstrated
in vitro cytotoxic activity against solid tumor types including ovarian cancer.
- Our laboratory demonstrated L-ASP inhibits vascular remodeling and modulates
heterotypic adhesion interactions between ovarian cancer cells and endothelial cells.
Results indicate L-ASP has the ability to modify the local tumor microenvironment.
- Epithelial ovarian cancer requires neovascularization for growth and metastasis.
Anti-angiogenesis agents show promise in treatment of recurrent disease.
- The pegylated form of L-ASP, pegaspargase, (Sigma Tau ONCASPAR (Trademark)) is shown to
deplete serum levels of asparagine and is approved for ALL. ONCASPAR is in clinical
trial with gemcitabine for pancreatic cancer and other solid tumors.
- Recommended dose of pegaspargase in ALL is 2,500 IU/m^2 every two weeks intramuscular
(IM)/intravenous (IV). IM dosing of 2,000 IU/m^2 every two weeks has been studied in a
phase I protocol with various solid tumors.
- Demonstration of safety and anti-angiogenic activity will lead to combination studies.
- To preliminarily evaluate the anti-tumor activity of pegaspargase, 2,000 IU/ m^2 every
two weeks intravenous (IV) (or intramuscular (IM)) and explore associations with
toxicity and clinical outcome.
- To evaluate the safety of pegaspargase in patients with recurrent or refractory
ovarian, fallopian tube, and/or primary peritoneal cancer.
- To explore changes in circulating angiogenic cytokines after treatment with
- To measure apoptosis and proliferation in tumor (or malignant effusion) by protein
array before and during therapy.
- To evaluate changes in tumor vascularity using dynamic contrast enhanced (DCE) magnetic
resonance imaging (MRI).
- Women with epithelial ovarian cancer, fallopian tube cancer, and/or primary peritoneal
cancer that is persistent, relapsed and/or refractory to prior therapy.
- There is no limit to number of prior treatment regimens. Patients may not have
previously received L-ASP.
- Women must have disease amenable to biopsy or malignant effusions (pleural effusion or
ascites) that may be serially tapped.
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2.
- Evidence of adequate end organ function and normal coagulation parameters (prothrombin
time (PT), activated partial thromboplastin time (aPTT)).
- Women will receive 2,000 IU/m^2 of pegaspargase intravenously every two weeks in 28-day
cycles until disease progression, excessive toxicity, or withdrawal from study.
- Biopsy of tumor and dynamic contrast-enhanced-magnetic resonance imaging (MRI) will be
performed prior to starting pegaspargase (mandatory) and after 6 weeks of treatment
- Clinical outcome will be measured and correlated with biological endpoints.
- Research blood samples will be taken to assess changes in serum vascular endothelial
growth factor (VEGF), interleukin-6 (IL6), and interleukin-8 (IL8).
- Blood will be collected to evaluate circulating endothelial cells.
- Patients will be seen in clinic every 4 weeks and outcome measured every other cycle.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
6 Month Progression Free Survival
Proportion of patients able to attain a 6 month progression free survival. Progressive disease is defined as >20% increase in the sum of the longest diameter of all target lesions, or the unequivocal increase in size of non-measurable lesions agreed upon by two investigators, or the appearance of new lesions.
Elise C Kohn, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|