Intraperitoneal Infusion of Autologous Monocytes With Sylatron (Peginterferon Alfa-2b) and Actimmune (Interferon Gamma-1b) in Women With Recurrent or Refractory Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
Condition: Fallopian Tube Cancer; Ovarian Cancer; Primary Peritoneal Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Peritoneal Neoplasms
Intervention: Autologous Monocytes + ACTIMMUNE + SYLATRON
Intervention description: The autologous monocytes cell product in 250ml total volume of investigational combination (monocytes + ACTIMMUNE + SYLATRON) is infused via the intraperitoneal catheter over 30-60 min +/- 10 min every 28 days +/- 7 days until disease progression, limiting toxicity, intercurrent medical issues, or patient withdrawal. Dosing is based on a dose escalation design including an expansion cohort at the maximum tolerated dose (MTD).
Intervention MeSH terms: Interferon-gamma
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunotherapy; Adoptive Cell Therapy; Carcinomatosis; CA125

Summary:

      Ovarian cancer is a leading cause of cancer death in women. Monocytes are white blood cells
      that slow tumor growth. Interferons (IFNs) are molecules that help immune cells fight cancer.
      Researchers want to stimulate monocytes with IFNs. They want to test if these stimulated
      monocytes combined with the drugs Sylatron and Actimmune can shrink tumors and slow the
      progression of cancer.

      Objective:

      To test how well IFN stimulated monocytes, with Sylatron and Actimmune, kill tumor cells.

      Eligibility:

      Women ages 18 and older with certain ovarian, fallopian tube, or peritoneal cancers

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood and urine tests

      Scan

      Results or sample from previous biopsy

      Participants may have a tumor sample taken.

      Participants who do not have a port will have a catheter placed inside the abdominal cavity.
      It will be used to give the treatment.

      Participants will have visits for 4 days of each 28-day cycle. This includes overnight
      observation.

      Participants with ascites fluid in their abdominal cavity will have it sampled twice.

      Each cycle, participants will have:

      Blood tests

      Leukapheresis. Some blood is removed and put through a machine that separates out the
      monocytes. The rest of the blood is returned to the body.

      Infusion of the monocytes and study drugs

      Participants will have weekly phone calls in Cycle 1 and scans every 2 cycles.

      Participants will continue treatment until they can no longer tolerate it or their cancer
      gets worse.

      Participants will have a visit about 1 month after stopping treatment, then monthly phone
      calls.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Patients must have histologically or cytologically confirmed advanced metastatic or
             unresectable epithelial ovarian cancer, primary peritoneal cancer or fallopian tube
             cancer that is relapsed and resistant (recurred less than 6 months after chemotherapy)
             or refractory (progressed on chemotherapy) to prior platinum- and taxane-based
             standard care systemic regimen. Or patients who are eligible for aditional platinum
             therapy. Histopathologic diagnosis must be confirmed in the Laboratory of Pathology
             (LP), National Cancer Institute (NCI).

          -  Patients must have measurable or evaluable disease. Measurable disease is defined as
             at least one lesion that can be accurately measured in at least one dimension (longest
             diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as
             greater than or equal to 20 mm with conventional techniques or as greater than or
             equal to 10 mm with spiral computed tomography (CT) scan.

          -  Patients must be at least 4 weeks from previous therapy (chemotherapy, hormonal
             therapy, and radiation therapy, immunotherapy and monoclonal antibodies, alternative
             therapy or investigational therapeutic agents). There is no limitation on the amount
             of prior therapies allowed. Patients with ovarian cancer 4 weeks from previous therapy
             have been found to have normal monocyte function (unpublished).

          -  Patients who have had cranial radiation therapy need to have completed it greater than
             or equal to 8 weeks prior to enrollment.

          -  Patients are permitted to receive investigational imaging agents while on study.

          -  Patients who have had major surgery must be fully recovered and require a recovery
             period of greater than or equal to 4 weeks prior to enrolling on study.

          -  Age greater than or equal to 18 years. Because no dosing or adverse event data are
             currently available on the use of intraperitoneal monocytes, interferon (IFN)-alpha 2
             or IFN-gamma in patients <18 years of age, children are excluded from this study, but
             will be eligible for future pediatric trials.

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1
             (Karnofsky greater than or equal to 70%).

          -  Adequate renal function, defined as serum creatinine less than or equal to 1.5 X upper
             limit of normal (ULN), or measured creatinine clearance greater than or equal to 60
             mL/min/1.73m^2.

          -  Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine
             aminotransferase (ALT) levels less than or equal to 3 X ULN and total bilirubin < 1.5
             X ULN, unless known diagnosis of Gilbert's syndrome, where bilirubin less than or
             equal to 5 mg/dl will be permitted. Gilbert's syndrome will be defined as elevated
             unconjugated bilirubin, with conjugated (direct) bilirubin within the normal range and
             less than 20% of the total. Total bilirubin will be permitted up to 5 mg/dl, if
             patients have historical readings consistent with the definition of Gilbert's syndrome
             prior to entering study.

          -  Adequate bone marrow function, defined as absolute neutrophil (ANC) greater than or
             equal to 1,500/mm^3 (greater than or equal to 1.5 X106/L), platelet count greater than
             or equal to 75,000/mm^3 (greater than or equal to 75 X10^6/L), and hemoglobin greater
             than or equal to 8 g/dL (transfusion to obtain hemoglobin greater than or equal to 8
             g/dL is allowed).

          -  The effects of intraperitoneal monocytes, IFN-alpha 2, and IFN-gamma on the developing
             human fetus are unknown. For this reason and because interferons based on animal data
             may cause fetal harm, women of child-bearing potential (excludes women with recurrent
             ovarian cancer) and men must agree to use adequate contraception (hormonal or barrier
             method of birth control; abstinence) prior to study entry and for the duration of
             study participation. Should a woman become pregnant or suspect she is pregnant while
             she is participating in this study, she should inform her treating physician
             immediately.

          -  Ability of subject to understand and the willingness to sign a written informed
             consent document.

        EXCLUSION CRITERIA:

          -  Patients who are receiving any other investigational agents (with exception of imaging
             agents as indicated above in the inclusion criteria).

          -  Patients cannot have previously been treated with interferons (e.g., for chronic
             active hepatitis).

          -  Lack of recovery of prior adverse events to Grade less than or equal to 1 severity
             (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE]
             v 4.03) (except alopecia) due to therapy administered prior to the initiation of study
             drug dosing. Stable persistent grade 2 peripheral neuropathy may be allowed as
             determined on a case-bycase basis at the discretion of the Investigator as interferon
             has not been shown to cause or exacerbate peripheral neuropathy.

          -  Patients with active infection will not be eligible, but may become eligible once
             infection has resolved and at least 7 days have elapsed after antibiotics use was
             completed.

          -  Concomitant chronic (daily or almost daily for greater than or equal to 1 month prior)
             use of steroids or non-steroidal anti-steroidal anti-inflammatory drugs (NSAIDS).

          -  Patients with a recent history (within last 5 years) of autoimmune disease or
             inflammatory diseases will be excluded, because interferons may worsen these
             conditions. Exceptions will be allowed for vitiligo and hypothyroidism that has been
             stable on thyroid replacement medications for >6 weeks.

          -  Impaired cardiac function or clinically significant cardiac disease including the
             following:

               -  New York Heart Association class III or IV congestive heart failure

               -  Myocardial infarction within the last 12 months

               -  Subjects known to have impaired left ventricular ejection fraction (LVEF)
                  according to institutional standards

          -  History of allergic reactions attributed to compounds of chemical or biologic
             composition similar to interferons or other agents used in the study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations within the last 12 months that
             would limit compliance with study requirements. Patients with history of
             neuropsychiatric disorders or Major Depressive Disorder (Diagnostic and Statistical
             Manual of Mental Disorders, Fifth Edition (DSM 5) definition:
             http://dsm.psychiatryonline.org/doi/full/10.1176/appi.books.9780890425596.dsm04)
             requiring medical treatment will not be eligible to enroll, based on the black box
             warning (SYLATRON (peginterferon alfa-2b) for injection, for subcutaneous use. Merck
             Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ).
             Exception to this is if patients experienced transient post-partum depression that
             resolved and patient has been off treatment for >10 years. Patients who are taking
             oral anti-depressants for normal sadness, bereavement, or grief will not be excluded.

          -  Pregnant women are excluded from this study because interferons based on animal data
             may cause fetal harm. Because there is an unknown but potential risk for adverse
             events in nursing infants secondary to treatment of the mother with interferons,
             breastfeeding should be discontinued if the mother is treated with intraperitoneal
             interferons. These potential risks may also apply to other agents used in this study.

          -  Patients on combination antiretroviral therapy for the treatment of HIV are ineligible
             because of the potential for pharmacokinetic interactions with interferons alfa and
             gamma.

          -  Patients receiving any medications or substances that are potent inhibitors or
             inducers of Cytochrome P450 1A2 (CYP1A2) or Cytochrome P450 2D6 (CYP2D6) are
             ineligible.