A Trial of Vigil for Participants With Ovarian Cancer

This is a multicenter, randomized, double-blind, placebo-controlled, Phase 2 study of maintenance Vigil Ovarian (gemogenovatucel-T) engineered autologous tumor cells (EATC) in women with Stage IIIb, IIIc or IV high-grade papillary serous/ clear cell / endometrioid ovarian, fallopian tube or primary peritoneal cancer. Subjects will have had a minimum of 4 and a maximum of 12 doses of Vigil prepared and stored from ovarian tumor cells obtained at the time of primary surgical debulking or initial diagnostic / evaluative laparoscopy (tissue for immunotherapy manufacture must be procured prior to initiation of neoadjuvant chemotherapy). An equal number of placebo doses will be manufactured. Subjects eligible for randomization will have achieved a clinically defined complete response following primary surgery and adjuvant chemotherapy. Clinical complete response (cCR) is defined as no evidence of maligancy on chest x-ray and CT scan or MRI of the abdomen and pelvis, CA-125 antigen level ≤ units/mL, and no findings on physical examination or symptoms suggestive of active cancer.

Investigational treatment must start no less than 3 weeks and no more than 8 weeks following completion of chemotherapy.

Approximately 86 subjects will be randomized 1:1 to to Group A (Vigil 1.0 X 10e7 cells/injection) or Group B (placebo). Randomization will be stratified by (i) extent of surgical cytoreduction (complete/microscopic versus macroscopic residual disease) and (ii) neoadjuvant versus adjuvant chemotherapy. Participants will receive Vigil or placebo by intradermal injection once a month for at least 4 and up to a maximum of 6 doses determined by the number of doses of Vigil manufactured for that subject.

Participants will be managed in an outpatient setting. Image assessment with chest x-ray and CT scan or MRI of the abdomen and pelvis will be completed every 3 months in Years 1-3, then every 6 months in Years 4 and 5 and yearly through Year 10. At the time the participant recurs, the participant will enter long term follow-up for survival status and post treatment therapies received.

Inclusion criteria

Subjects will be eligible for tissue procurement for the Vigil manufacturing process if they meet all of the following criteria:

• Presumptive Stage IIIb, IIIc or IV high-grade papillary serous/clear cell/endometrioid ovarian, fallopian tube or primary peritoneal cancer.
• No chemotherapy prior or investigational agents prior to tissue acquisition for Vigil manufacture.
• No other malignancy (excluding surgically cured nonmelanoma carcinomas of the skin and carcinoma in situ cervix) unless in remission for ≥ 2 years.
• Anticipated availability of a cumulative mass of ~30 grams tissue ("golf-ball" size or approximately 3cm disease on CT scan) at time of diagnostic laparoscopy or primary surgical debulking. Infiltrating lumen (bowel, fallopian tube, urethra) tissue should not be used as Vigil immunotherapy material to minimize risk of bacterial contamination.
• ECOG performance status (PS) 0-2 prior to diagnostic laparoscopy or debulking laparotomy.
• No prior history of hypersensitivity reactions (HSR) with taxanes or platinums.
• No prior history of allergies or sensitivities to gentamicin.
• Female, 18 years of age or older.
• Ability to understand and the willingness to sign a written informed consent document for tissue harvest.

Subjects will be registered in this study if they meet all of the following inclusion criteria:

• Histologically confirmed Stage IIIb, IIIc or IV high-grade papillary serous/clear cell/endometrioid ovarian, fallopian tube or primary peritoneal.
• Completion of primary surgical debulking including hysterectomy and bilateral salpingo oophorectomy, and at least 5 but no more than 8 cycles of platinum / taxane adjuvant chemotherapy or chemotherapy as per Category 1 recommendations of the NCCN guidelines, including 5-8 cycles adjuvant intraperitoneal + intravenous (IP/IV) chemotherapy, or 5-8 cycles of intravenous chemotherapy divided and administered as neoadjuvant and adjuvant therapy flanking primary debulking surgery.
• Clinically defined complete response (cCR) following completion of primary surgical debulking and eligible chemotherapy. cCR defined as no evidence of malignancy on chest x-ray (CT scan is acceptable) and CT scan or MRI of the abdomen and pelvis, normal physical examination, CA-125 antigen level ≤ 35 U/ml (assessed ≥ 2 weeks following removal of catheter in subjects receiving intraperitoneal/intravenous chemotherapy) and no findings on physical examination or symptoms suggestive of active cancer.
• Subjects must have initiated adjuvant chemotherapy no more than 8 weeks following primary debulking surgery.
• Successful manufacturing of at least 4 doses (vials) of Vigil and placebo.
• Recovered from all clinically relevant toxicities related to prior therapy (including neuropathy ≤Grade 2).
• ECOG performance status (PS) 0-1.
• Normal organ and marrow function as defined below: Absolute granulocyte count ≥ 1,500/mm^3, Absolute lymphocyte count ≥ 500/mm^3, Platelets ≥ 75,000/mm^3, Total bilirubin ≤ 2 mg/dL, AST(SGOT)/ALT(SGPT)≤ 2x institutional upper limit of normal, Creatinine < 1.5 mg/dL
• Ability to understand and the willingness to sign a written informed protocol specific consent.

Exclusion criteria

Subjects will be excluded from this study if they meet any of the following criteria (at the time of tissue procurement or at randomization):

• Surgery involving general anesthesia, radiotherapy, immunotherapy, or investigational agents within 4 weeks prior to randomization.
• Histologically confirmed papillary serous adenocarcinoma of the uterus or disease involving myometrium/endometrium.
• Systemic immunosuppressive therapy within 14 days of randomization.
• Subjects requiring chronic steroid or immunosuppressive regimens are excluded except inhaled / intranasal steroids and short term systemic steroids <30 days duration and ≤0.25 mg/kg prednisone-equivalent per day are allowed.
• Congestive heart failure (NYHA Class II, III, or IV), unstable angina, ventricular or hemodynamically significant atrial arrhythmia, or cardiovascular disease such as stroke or myocardial infarction (current or within the past 6 months).
• Psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects with history of brain metastases.
• Subjects with known HIV or chronic Hepatitis B or C infection.
• Prior solid organ or bone marrow transplant.
• History of or active autoimmune disease (e.g., autoimmune neutropenia, thrombocytopenia, or hemolytic anemia, systemic lupus erythematosus, Sjogren's syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, Addison's disease, Hashimoto's thyroiditis, or Graves disease). Persons with vitiligo are not excluded. Diabetics are not excluded if the condition is well controlled.