Title
Oregovomab Plus Chemo in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer Following Optimal Debulking Surgery
A Multicenter Phase 3, Double-Blind, Placebo-Controlled Study Comparing Chemo-Immunotherapy (Paclitaxel-Carboplatin- Oregovomab) vs Chemotherapy (Paclitaxel-Carboplatin- Placebo) in Patients With Advanced Epithelial Ovarian, Fallopian Tube or Peritoneal Carcinoma
Phase
Phase 3Lead Sponsor
OncoQuest Pharmaceuticals Inc.Study Type
InterventionalStatus
RecruitingIntervention/Treatment
Oregovomab Paclitaxel Carboplatin ...Study Participants
602Study to compare the safety and efficacy of oregovomab versus placebo, administered in combination with specific cycles of a standard six-cycle chemotherapy regimen (paclitaxel and carboplatin), for the treatment of subjects with newly diagnosed advanced ovarian cancer who have undergone optimal debulking.
Phase 3 double-blind, placebo-controlled, multi-center study to compare the safety and efficacy of four administrations of oregovomab 2 mg IV versus placebo, administered in combination with specific cycles of a standard six-cycle chemotherapy regimen (paclitaxel and carboplatin), for the treatment of subjects with newly diagnosed ovarian cancer who have undergone optimal debulking surgery and are either pending initiation of chemotherapy (Cohort 1 - Primary Surgery) or resumption of another three cycles of chemotherapy, having already completed three cycles of neoadjuvant chemotherapy (Cohort 2 - NACT + Interval Surgery).
For Cohort 1 - Primary Surgery, 372 subjects randomized in a 1:1 ratio (i.e., chemotherapy with oregovomab or chemotherapy with placebo). For Cohort 2 - NACT + Interval Surgery, 230 subjects will be randomized in a 1:1 ratio (i.e., chemotherapy with oregovomab or chemotherapy and placebo).
2 mg, dissolved in 2 mL of 0.9% Sodium Chloride Injection USP, then added to 50 mL of Sodium Chloride Injection USP infused over 20 ± 5 minutes
2 mg, dissolved in 2 mL of 0.9% Sodium Chloride Injection USP, then added to 50 mL of Sodium Chloride Injection USP infused over 20 ± 5 minutes
Six (6) 21-day cycles of chemotherapy with oregovomab given at four (4) cycles (Cycle 1, Cycle 3, Cycle 5, and Cycle 5 plus 12 weeks).
Six (6) 21-day cycles of chemotherapy with placebo comparator given with chemotherapy at four (4) cycles (Cycle 1, Cycle 3, Cycle 5, and Cycle 5 plus 12 weeks).
In Cohort 2 - NACT + Interval Surgery, subjects must already have received three (3) cycles of paclitaxel and carboplatin neoadjuvant therapy. Subjects in Cohort 2 - NACT + Interval Surgery will receive three (3) cycles of chemotherapy with oregovomab given at four (4) cycles (Cycle 4, Cycle 6, Cycle 6 plus 6 weeks and Cycle 6 plus 18 weeks).
In Cohort 2 - NACT + Interval Surgery, subjects must already have received three (3) cycles of paclitaxel and carboplatin neoadjuvant therapy. Subjects in Cohort 2 - NACT + Interval Surgery will receive three (3) cycles of chemotherapy with placebo comparator given at four (4) cycles (Cycle 4, Cycle 6, Cycle 6 plus 6 weeks and Cycle 6 plus 18 weeks).
Major Inclusion Criteria: Adults 18 years old or older. Newly diagnosed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin FIGO Stage III or IV disease. Histologic epithelial cell types: high grade serous adenocarcinoma, high grade endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise specified (N.O.S.). Completed debulking surgery (either primary debulking surgery or interval debulking surgery at the discretion of the investigator). Debulking surgery must be optimal, R1 or R0 (defined as R1, macroscopic no greater than 1 cm in diameter, or R0, microscopic or no evidence of tumor). Preoperative serum CA- 125 levels ≥ 50 U/mL. Adequate bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1,500/µL Platelets greater than or equal to100,000/µL Hemoglobin greater than or equal to 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before first dose of study treatment). Adequate liver function: Bilirubin < 1.5 times upper limit normal (ULN) Lactate Dehydrogenase (LDH), SGOT/AST and SGPT/ALT < 2.5 times ULN Albumin >3.5 g/dL Adequate renal function: a. Creatinine less than or equal to1.5 times ULN ECOG Performance Status of 0 or 1. Major Exclusion Criteria: BRCA1 or BRCA2 germline gene mutation test result with: Positive, ambiguous or inconclusive result available within 28 days prior to starting study treatment, or Known BRCA1 and BRCA2 somatic mutations, and known positive germline, or Somatic Homologous Recombination Deficiency (HRD) who will receive PARP inhibitor front-line maintenance therapy. Subjects with mucinous adenocarcinoma and low- grade adenocarcinoma. Female subjects who are lactating and breastfeeding, or have a positive serum pregnancy test within 7 days prior to the first dose of study treatment (C1D1 for Cohort 1 or C4D1 for Cohort 2). Active autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), or ankylosing spondylitis requiring active disease modifying treatment. Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab, paclitaxel, or carboplatin. Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc. (see Appendix G). Chronic therapeutic corticosteroid use, defined as > 5 days of prednisone or equivalent, with the exception of inhalers or those on a pre-planned steroid taper. (Note: Premedication with corticosteroids per institutional standard of care is allowed.) Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia. Anticipated treatment with any other anti-cancer medications, including bevacizumab, poly (ADP- ribose) polymerase (PARP) inhibitors, or any investigational agent(s) during the study.
