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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer

Intervention / Treatment
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* Biological: OC-L/Montanide ISA 51 VG
* Biological: Ampligen
* Biological: Prevnar


Participation Criteria
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Eligibility Criteria
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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: Platelets<100,000/mm 3 WBC < 2,500/mm3 Absolute Neutrophil Count (ANC) < 1,500/mm3 Absolute lymphocyte count <200/mm 3 Hematocrit < 30%

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2: Arm A<br>10 patients will receive vaccine (OC-L, an autologous vaccine comprised of autologous oxidized tumor cell lysate, admixed with Montanide ISA 51 VG) injected by intradermal/subcutaneous injection in both groin regions. | Biological: OC-L/Montanide ISA 51 VG<br>* All subjects will receive OC-L/Montanide ISA 51 VG) on day 0, 14,28,42 and 56 with a +/- 5 day window. The vaccine will be divided in two or more intradermal/subcutaneous injections in the groin areas bilaterally.<br>Biological: Prevnar<br>* A vaccine against Pneumococcus pneumoniae will be given intramuscularly on Day 0 and 14 as positive control of immune responsiveness.<br>|
| Experimental: Phase 2: Arm B<br>10 patients will receive vaccine (OC-L, an autologous vaccine comprised of autologous oxidized tumor cell lysate, admixed with Montanide ISA 51 VG) injected by intradermal/subcutaneous injection in both groin regions, administered in combination with intravenous Ampligen. | Biological: OC-L/Montanide ISA 51 VG<br>* All subjects will receive OC-L/Montanide ISA 51 VG) on day 0, 14,28,42 and 56 with a +/- 5 day window. The vaccine will be divided in two or more intradermal/subcutaneous injections in the groin areas bilaterally.<br>Biological: Ampligen<br>* All subjects will receive intravenous Ampligen (200mg given by IV infusion 60 +- minutes) 3 times starting 2-3 days after each vaccine administration. Each of the 3 Ampligen (200 mg) infusions will be separated by 2-3 days.<br>Biological: Prevnar<br>* A vaccine against Pneumococcus pneumoniae will be given intramuscularly on Day 0 and 14 as positive control of immune responsiveness.<br>|
| Experimental: Phase 1<br>3 patients will be enrolled receiving the vaccine (tumor lysate/Montanide) plus Ampligen using a 3+3 approach. If no DLTs in the first three subjects, we will move to phase II; if one 1/3 subject develops DLTs, we will enroll 3 additional subjects; if 2/6 subjects develop DLTs, we will discontinue the study. Following completion of run---in phase I (3 or 6 subjects), we will transition to Phase 2. | Biological: OC-L/Montanide ISA 51 VG<br>* All subjects will receive OC-L/Montanide ISA 51 VG) on day 0, 14,28,42 and 56 with a +/- 5 day window. The vaccine will be divided in two or more intradermal/subcutaneous injections in the groin areas bilaterally.<br>Biological: Ampligen<br>* All subjects will receive intravenous Ampligen (200mg given by IV infusion 60 +- minutes) 3 times starting 2-3 days after each vaccine administration. Each of the 3 Ampligen (200 mg) infusions will be separated by 2-3 days.<br>Biological: Prevnar<br>* A vaccine against Pneumococcus pneumoniae will be given intramuscularly on Day 0 and 14 as positive control of immune responsiveness.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Safety will be established by grading the observed toxicities using the NCI Common Toxicity Criteria (CTC Version 4.0). All toxicities observed within 30 days of last vaccination will be included. All patients that receive at least one vaccination will be included in the toxicity analysis. | within 30 days of last vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Response | Immune response will be evaluated by IFN-g ELISPOT analysis of tumor-reactive T cells, and in HLA-A2+ subjects, by tetramer analysis of Her-2 specific T cells in peripheral blood. Response is defined by a > 3 fold increase relative to pre-vaccination. | within 30 days of vaccination | 
| Clinical Response | Clinical Response will be estimated using immune related response criteria ir(RC) | within 30 days of vaccination |