Effect of Acetylcysteine With Topotecan Hydrochloride on the Tumor Microenvironment in Patients With Persistent or Recurrent High Grade Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
Condition: Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
MeSH terms: Carcinoma; Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Recurrence
Intervention: Topotecan Hydrochloride; Topotecan Hydrochloride; Acetylcysteine
Intervention description: Given IV; Given IV; Given IV and PO
Intervention MeSH terms: Acetylcysteine; Topotecan; N-monoacetylcystine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 1.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies the effects of acetylcysteine and topotecan
      hydrochloride on the tumor microenvironment, or cells that make up a tumor, compared to
      topotecan hydrochloride alone in patients with ovarian, fallopian tube, or primary peritoneal
      cancer that has not responded to treatment (persistent) or has returned after a period of
      improvement (recurrent) and is high grade (likely to grow and spread quickly). Research has
      shown that cancer cells may be able to convert nearby normal cells into cancer cells.
      Acetylcysteine may stop this from happening. Topotecan hydrochloride is a chemotherapy drug
      used to treat ovarian cancer, and may help acetylcysteine work better. This trial studies the
      effect of acetylcysteine and topotecan hydrochloride on the tumor microenvironment to see if
      they can help make it more difficult for tumor cells to grow.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient must have persistent or recurrent high grade endometrioid or serous ovarian,
             primary peritoneal or fallopian tube carcinoma. Histologic documentation of the
             original primary tumor is required via the pathology report.

          2. All patients must have measurable disease that is amenable to biopsy. Measurable
             disease is defined as at least one lesion that can be accurately measured in at least
             one dimension (longest dimension to be recorded). Each lesion must be ≥20 mm when
             measured by conventional techniques including palpation, plain film x-ray, CT, and
             MRI, or ≥ 10 mm when measured by high resolution CT.

          3. Patient must have at least one target lesion to be used to assess response on this
             protocol as defined by RECIST 1.1. Tumors within a previously irradiated field will be
             designated as non-target lesions unless progression is documented or a biopsy is
             obtained to confirm persistent disease at least 90 days following completion of
             radiation therapy.

          4. Patients must have a GOG performance status of 0, 1, or 2.

          5. Patients must be free of active infections requiring antibiotics, with the exception
             of uncomplicated urinary tract infections (UTIs).

          6. Any hormonal therapy directed at the tumor must be discontinued at least one week
             prior to initiation of therapy. Continuation of hormone replacement therapies is
             permitted.

          7. Any other prior therapy directed at the tumor, including immunologic agents, must be
             discontinued at least 3 weeks prior to initiation of therapy.

          8. Patients must have had at least one prior platinum/taxane combination chemotherapeutic
             regimen for management of primary disease containing carboplatin, cisplatin, or
             another organoplatin compound. This initial treatment may include intraperitoneal
             therapy, high dose therapy, consolidation, noncytotoxic agents, or extended therapy.

          9. Patients must be platinum resistant- defined as progressive disease while receiving
             platinum therapy or within 6 months of completing first line platinum therapy or
             patients who have progressive disease after two lines of platinum based treatment.

               1. Cytotoxic regimens are any that include agents that target the genetic and/or
                  mitotic apparatus of the dividing cells, resulting in dose limiting toxicity to
                  the bone marrow or gastrointestinal mucosa

               2. Patients are allowed to receive, but not required to receive biologic
                  (noncytotoxic) therapy as part of their treatment regimen, e.g. bevacizumab.

         10. Patients Must Have Adequate:

               1. Bone Marrow Function: Absolute Neutrophil Count greater than or equal to
                  1000/mcl. Platelets greater than or equal to 100,000/mcl. Hemoglobin greater than
                  10 g/dl. (Patients may be transfused to achieve this hemoglobin.)

               2. Renal Function: creatinine less than or equal to 1.5 x upper limit of normal,
                  CTCAE v 4.0 grade 1.

               3. Hepatic Function: bilirubin less than or equal to 1.5 x upper limit of normal,
                  CTCAE v 4.0 grade 1. Asparate transaminase (AST) and alkaline phosphatase less
                  than or equal to 2.5 x upper limit of normal, CTCAE v 4.0 grade 1.

               4. Coagulation: PT, PTT less than or equal to 1 to 1.5 x upper limit of normal CTCAE
                  v 4.0 grade 1 except for patients on therapeutic anticoagulation.

               5. Neurologic Function: neuropathy (sensory and motor) less than or equal to CTCAE v
                  4.0 grade 1.

         11. Patients must have signed an approved informed consent and authorization permitting
             release of personal health information.

         12. Patients must meet pre-entry requirements as specified.

         13. In the unlikely event that patients are still of childbearing potential, these
             patients must have a negative serum pregnancy test within 72 hours prior to initiating
             protocol therapy and be practicing an effective form of contraception during protocol
             therapy and for at least 4 weeks following completion of protocol therapy.

         14. Patients must be 18 years of age or older.

         15. Patients must not be receiving any other investigational agent.

         16. Patients must be able to swallow whole pills. -

        Exclusion Criteria:

          1. Patients who have had previous treatment with topotecan.

          2. Patients who have had more than 4 prior chemotherapy regimens.

          3. Patients who have received radiation to more than 25% of marrow-bearing areas.

          4. Patients with a history of other invasive malignancies are excluded if there is any
             evidence of other malignancy being present within the last 3 years.

          5. Patients who have received prior chemotherapy for any abdominal or pelvic tumor other
             than for treatment of ovarian carcinoma within the last 3 years are excluded. Patients
             may have received prior chemotherapy for localized breast cancer, provided that it was
             completed more than three years prior to registration and the patient remains free of
             recurrent of metastatic disease.

          6. Pregnant or nursing women or women of childbearing potential unless using effective
             contraception as determined by the investigator. -