Clinical trial NCT01313078
Conditions: Ovarian Neoplasms Fallopian Tube Neoplasms Primary Peritoneal Neoplasms
Keywords: Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer Relapsed or Refractory Pegaspargase Pegylated L-Asparaginase
Sponsor: National Cancer Institute (NCI)
Start date: 2010-01-01; Completion date: 2011-09-01
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Background:

\- The best treatment for ovarian and related female reproductive tract cancers is not yet known for patients whose disease has not responded to or has recurred after standard treatment. The cancer treatment drug pegaspargase (ONCASPAR (Trademark)), which works differently from standard chemotherapy, has been approved to treat leukemia and has been given to a small number of patient with ovarian and other types of cancer. Because pegaspargase may reduce the development of cancer cells and blood vessel cells that contribute to cancer growth and ability to spread, treatment with pegaspargase could shrink ovarian cancer tumors and help ovarian cancer patients live longer and with fewer symptoms from their disease.

Objectives:

\- To evaluate the safety and effectiveness of pegaspargase in patients with recurrent or refractory ovarian cancer, fallopian tube cancer, and/or primary peritoneal cancer.

Eligibility:

\- Women at least 18 years of age who have been diagnosed with epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that has not responded to at least one operation, chemotherapy, and/or radiotherapy.

Design:

* Before the start of the study, participants will be screened with a medical history, blood tests, imaging scans of the affected areas, tumor biopsies, and other tests as directed by the study doctors.
* Participants will receive an infusion of pegaspargase on Day 1 and Day 15 of each 28-day cycle.
* Participants will have dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at the start of the study, before beginning pegaspargase, and again 6 weeks into the treatment. This test will determine if pegaspargase is affecting blood flow to the cancer site.
* Participants will have a computed tomography scan or other imaging every other cycle (approximately every 8 weeks) to determine whether the therapy is affecting the cancer site.
* The treatment will be repeated as long as the participant tolerates the medication and his or her cancer is either steady or improving.

Detailed description:
Background:

* 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.

Primary Objectives:

* 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.

Secondary Objectives:

* To explore changes in circulating angiogenic cytokines after treatment with pegaspargase.
* 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).

Eligibility:

* 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)).

Design:

* 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 (optional).
* 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.

Arms: arm 1: Pegaspargase 2000 IU/m\^2 intramuscular or intravenously every 2 weeks
Interventions: intervention 1: Pegylated L-Asparaginase
Intervention descriptions: intervention 1: Pegaspargase 2000 IU/m\^2 intramuscular or intravenously every 2 weeks

Protocol documents: