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
Condition: Ovarian Neoplasms; Fallopian Tube Neoplasms; Primary Peritoneal Neoplasms
MeSH terms: Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Peritoneal Neoplasms
Intervention: Pegylated L-Asparaginase
Intervention description: Pegaspargase 2000 IU/m^2 intramuscular or intravenously every 2 weeks
Intervention MeSH terms: Asparaginase; Pegaspargase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; Relapsed or Refractory; Pegaspargase; Pegylated L-Asparaginase

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  All patients 18 years and older with epithelial ovarian, fallopian tube, or primary
             peritoneal cancer that is persistent, relapsed or refractory to prior standard
             platinum and taxane-based therapy will be eligible. Tumor histology must be reviewed
             and confirmed by the National Cancer Institute (NCI) Laboratory of Pathology.
             Recurrent ovarian cancer is not a curable tumor. Patients who are platinum-sensitive
             and who, upon detailed informed consent, wish to consider this experimental regimen,
             will be considered.

          -  All patients must have measurable disease by Response Evaluation Criteria in Solid
             Tumors (RECIST) criteria. A sentinel lesion adequate for core biopsy through
             percutaneous route is ideal but not mandatory. Patients with a malignant pleural
             effusion or malignant ascites will be allowed to undergo a paracentesis or
             thoracentesis rather than core needle biopsy if the procedure may be performed safely.

          -  Patients must have a performance status of Eastern Cooperative Oncology Group (ECOG) =
             0, 1, 2

          -  Patients must have adequate end organ function:

               -  Absolute neutrophil count (ANC) greater than or equal to 1500/ mm^3

               -  Platelets greater than or equal to 100,000/ mm^3

               -  Serum creatinine less than or equal to 1.5 mg/dL, or if low, creatinine clearance
                  greater than or equal to 60 mL/min

               -  Total bilirubin less than or equal to 1.5 times the ULN (upper limit of normal)
                  unless a history of Gilbert's disease.

               -  Lipase and amylase less than or equal to 1.5 times the ULN

               -  Transaminases (aspartate aminotransferase (AST), alanine aminotransferase (ALT))
                  less than or equal to 2.5 times the ULN

               -  Fibrinogen greater than or equal to 0.75 times the LLN

               -  Prothrombin time (PT), partial thromboplastin time (PTT), and International
                  Normalized Ratio (INR) less than or equal to 1.5 times the ULN. Coagulation
                  parameters must be drawn peripherally.

          -  Patients must be at least 4 weeks from previous therapy (chemotherapy, hormonal
             therapy, and radiation therapy, alternative therapy, investigational agents, or a
             major surgical procedure). Patients must be 6 weeks from carboplatin- or mitomycin
             C-containing therapy. Exceptions: Raloxifene will be allowed for bone health and
             bisphosphonate therapy will be allowed for the rare situation of bone metastasis.

          -  There is no limit to the number of prior regimens patients may have received for the
             treatment of ovarian cancer.

          -  Patients must have recovered from any toxicity related to prior cancer therapy to
             Common Terminology Criteria for Adverse Events (CTCAE) grade 1, except for stable
             peripheral neuropathy, which must have recovered to grade 2 or better, and grade 2
             total white blood cell count when ANC is greater than or equal to 1500 (alopecia and
             hypertension exempted).

          -  Women of childbearing potential must agree to use adequate barrier contraception
             (interaction with oral contraceptives is unknown) prior to study entry, during therapy
             and for 3 months after completion of therapy and must have a negative pregnancy test.

          -  Patients must be able to give written informed consent.

        EXCLUSION CRITERIA:

          -  Evidence of severe or uncontrolled systemic disease or any concurrent condition which
             in the Investigator's opinion makes it unsafe for the patient to participate in the
             trial or which would jeopardize compliance with the protocol.

          -  Evidence of central nervous system (CNS) involvement. Patients with abnormal clinical
             exam or history will require a head computed tomography (CT) or magnetic resonance
             imaging (MRI).

          -  History of clinically symptomatic pancreatitis within the six months prior to
             enrollment.

          -  History of prior exposure to any formulation of L-asparaginase.

          -  Patients with a history of deep venous thrombosis or pulmonary embolism within the
             past 3 months, or pulmonary embolism within the past 6 months, history of recurrent
             clot or pulmonary embolism (PE), or those patients requiring ongoing full dose
             anticoagulation will be ineligible. Line prophylaxis with 1 mg warfarin daily will be
             allowed.

          -  Patients with active infection will not be eligible, but may become eligible once
             infection has resolved and they are at least 7 days from completion of antibiotics.

          -  Women who are pregnant and women actively breast-feeding will be excluded.

          -  Previous or current malignancies within the last 5 years, with the exception of
             cervical carcinoma in situ curatively treated, ductal or lobular carcinoma in situ
             curatively treated and without ongoing therapeutic intervention, and nonmelanomatous
             skin cancers curatively treated.

          -  No concomitant use of complementary or alternative medication or other agents
             (investigational or anti-cancer agents) will be allowed without approval of a
             principal investigator (PI) or associate investigator (AI). Every effort will be made
             to maximize patient safety and minimize changes in chronic medications.