A Clinical Trial of Autologous Oxidized Tumor Cell Lysate Vaccine For Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer

A Phase I/II Randomized Clinical Trial of Autologous Oxidized Tumor Cell Lysate Vaccine For Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer

This is a Phase I/II randomized study for subjects with recurrent ovarian, fallopian tube or primary peritoneal cancer to determine the feasibility and safety as well as immunogenicity of OC-L, an autologous vaccine comprised of autologous Oxidized tumor Cell Lysate (OC-L) administered by intradermal/subcutaneous injection in combination with Ampligen (poly-l:poly-C12U), a Toll-like receptor 3 agonist. Study duration is 24 months.

This is a Phase I/II randomized study for subjects with recurrent ovarian, fallopian tube or primary peritoneal cancer to determine the feasibility and safety as well as immunogenicity of OC-L, an autologous vaccine comprised of autologous Oxidized tumor Cell Lysate (OC-L) administered by intradermal/subcutaneous injection in combination with Ampligen (poly-l:poly-C12U), a Toll-like receptor 3 agonist. Study duration is 24 months. This study has two Phases eligible subjects enrolled in Phase 1 will receive the OC-L admixed with Montanide ISA 51 with intravenous Ampligen. Subjects enrolled in Phase II will be randomized to two ARMS. This randomized design will allow for the unbiased evaluation and comparison of immune response among the 2 treatment arms. patients will be randomized (10 per treatment arm) in blocks of size 4 or 6, such that treatment assignment will be balanced after each group of 4 or 6 patients has been randomized. ARM A 10 patients will receive OC-L. Arm b 10 patients will receive OC-L with Ampligen. Following each vaccination, subjects in Phase I and Arm B will be given intravenous Ampligen 3 times starting 2-3 days after each vaccine administration. All subjects will receive vaccine on Day 0, 14, 28, 42 and 56. Subjects will receive Prevnar on day 0 and day 14. Subjects will be treated till exhaustion of OC-L or disease progression whichever occurs first subjects will be contacted every 6 months for up to 5 years and then annually for survival. The OC-L study product is manufactured and quality tested at Cell and Vaccine Production Facility and then released to IDS, where it will be admixed with Montanide ISA 51 VG on day of vaccination.

Inclusion Criteria:

• Subject has recurrent ovarian (including low malignant potential), fallopian tube or primary peritoneal cancer and has already received front line platinum based chemotherapy prior to recurrence.
• Subject has had prior secondary cytoreductive surgery yielding tumor for Lysate preparation.
• Lysate must meet release criteria.
• Subject has a current largest tumor nodule that is >1 cm CT or MRI.
• Subject is 18 years of age or older.
• Subject has an ECOG performance status of <1.
• Subject has a life expectancy of >6 months.
• Subject must understand and sign the study specific informed consent.
• Subject may have received chemotherapy or other therapy after harvest of tumor and prior to enrollment but must have recovered from toxicities of prior chemotherapy or other therapy (to grade 2 or less).
• Subject may have received prior investigational therapy (including immune therapy).
• Subject may have received prior hormonal therapy.
• Subject may have received prior radiation therapy but must have completed such therapy prior to enrollment.
• Subject who screen fails can be re-enrolled if the causation of the screen fail has been corrected.

Exclusion Criteria:

• Subject for whom tumor lysate does not meet release criteria.

• Subject has a positive serum Yo antibody

• Subject has a chronic or acute hepatitis C infection.

• Subject has a chronic or acute hepatitis B infection.

• Subject has positive test result at the screening visit for one or more of the following: 1. HTLV-1/2 Antibody, 2. Anti-HIV 1/2 Antibody

• Subject requires or is likely to require more than a two-week course of corticosteroids for intercurrent illness. Subject must complete the course of corticosteroids 2 weeks before screening to meet eligibility.

• Subject has renal insufficiency as defined by a serum creatinine > 2.2 mg/dl. Note: If creatinine is greater than 1.5 x ULN, creatinine clearance must be greater than 50 ml/min.

• Subject with liver failure as defined by a serum total bilirubin > 2.0 and /or serum transaminases > 3X the upper limits of normal.

• Subject has any acute infection that requires specific therapy. Acute therapy must have been completed within seven days prior to study enrollment.

• Subject has a serious, non-healing wound, ulcer, or bone fracture.

• Subject has known allergies to reagents used in this study.

• Subject has organ allograft.

• Subject is receiving medications that might effect immune function. Use of H2 antagonists are prohibited, as are all antihistamines five days before and five days after each injection of study vaccine. However, NSAIDS including COX-2 inhibitors, acetaminophen or aspirin are permitted.

• Subject has clinical symptoms or signs of partial or complete gastrointestinal obstruction or requires parenteral hydration and/or nutrition.

• Subject has hematopoietic failure at baseline as defined by one of the following:

  1. Platelets<100,000/mm 3
  2. WBC < 2,500/mm3
  3. Absolute Neutrophil Count (ANC) < 1,500/mm3
  4. Absolute lymphocyte count <200/mm 3
  5. Hematocrit < 30%