advanced epithelial ovarian, fallopian tube or peritoneal carcinoma
Conditions
Interventions
Product Name: OREGOVOMAB
Product Code: MAB-B43.13
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Oregovomab
CAS Number: 213327-37-8
Current Sponsor code: MAb-B43.13
Other
Sponsors
CanariaBio Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adults 18 years old or older. 2. Subjects with newly diagnosed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin FIGO Stage III or IV disease. 3. Eligible 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.). 4. Completed debulking surgery (either primary debulking surgery or interval debulking surgery at the discretion of the investigator), as defined below: a. For subjects who undergo primary debulking surgery (Cohort 1 - Primary Surgery): i. Subject must receive initial dose of paclitaxel 175 mg/m2 given intravenously, and carboplatin AUC 6 IV every 3 weeks (21 days) for 6 cycles. Carboplatin total dose given as 5 consecutive daily pulse doses, for subjects who experiences significant grade 3 or higher emesis. Subsequent dose modifications will be instituted per protocol. Cycle 1 of chemotherapy ± oregovomab/placebo must be anticipated to occur within 6 weeks +/- 5 days after primary debulking surgery, and ii. The primary debulking surgery is optimal, R1 or R0 (defined as R1, macroscopic less than 1 cm in diameter, or R0, microscopic or no evidence of tumor). Assessment of intra-abdominal optimal debulking will be determined at the time of the surgical procedure and not by postsurgical imaging (i.e., CT scan). Assessment of intra-abdominal optimal debulking will be determined at the time of the surgical procedure and not by post-surgical imaging (i.e., CT scan). b. For subjects who will undergo interval debulking surgery (IDS) (Cohort 2 – NACT+Interval Surgery): i. Prior to interval debulking surgery (IDS), subject must have received neoadjuvant treatment with 3 cycles of paclitaxel and carboplatin. a. Paclitaxel must have been started at an initial does of 175 mg/m2 given intravenously (IV) every 3 weeks (21 Days). If the subject experienced grade 3 or 4 adverse events with paclitaxel 175mg/m2, dose reduction to 135 mg/m2 is allowed for cycles 2 and/or 3. b. Carboplatin initial dose must have been an area under the curve (AUC) 5-6 IV approximately every 3 weeks (21 Days). ii. Once subjects are enrolled on the protocol, they must receive paclitaxel 175mg/m2 IV and carboplatin AUC 5-6 IV every 3 weeks starting cycle 4. Subsequent dose modifications will be instituted per protocol. Cycle 4 of chemotherapy ± oregovomab/placebo must be anticipated to occur within 6 weeks after interval debulking surgery, and iii. The interval debulking surgery is optimal, R1 or R0 (defined as R1, macroscopic less than 1 cm in diameter, or R0, microscopic or no evidence of tumor). Assessment of intra-abdominal optimal debulking will be determined at the time of the surgical procedure and not by post-surgical imaging (i.e. CT scan) 5. Suitable venous access for the study-required procedures. 6. CA-125 levels: a. Cohort 1 – Primary Surgery: Preoperative serum CA-125 levels = 50 U/mL, or b. Cohort 2 – NACT + Interval Surgery: serum CA-125 levels = 50 U/mL prior to first neoadjuvant chemotherapy administration (chemotherapy cycle #1). 7. Adequate bone marrow function: a. Absolute neutrophil count (ANC) = 1,500/µL b. Platelets = 100,000/µL 8. Hemoglobin = 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before first dose of study treatment). 9. Adequate liver function: a. Bilirubin < 1.5 times upper limit of normal (ULN) b.
Exclusion criteria
Exclusion criteria: 1. BRCA1 or BRCA2 germline gene mutation test result with: a. Pathogenic, ambiguous or inconclusive result available within 28 days prior to starting study treatment. Subjects with BRCA1 or BRCA2 variants of uncertain significance can enroll onto the study as long as there is no intent to administer PARP inhibitors for front-line maintenance therapy, or b. Known BRCA1 and BRCA2 somatic mutations, if testing is performed. 2. Known Somatic Homologous Recombination Deficiency (HRD) who will receive PARP inhibitor front-line maintenance therapy. Subjects with somatic HRD are eligible as long as there is no intent to administer PARP inhibitor front-line maintenance therapy. 3. Subjects with mucinous adenocarcinoma, carcinosarcoma, tumors with neuroendocrine features and low-grade adenocarcinoma. 4. 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). 5. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol. 6. Active autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, MS, or ankylosing spondylitis requiring active disease modifying treatment. 7. Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab, paclitaxel, or carboplatin. 8. Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc. 9. 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.) 10. Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia. 11. Clinically significant active infection(s) at the time of screening. 12. Any of the following conditions (on-study testing is not required unless it is required by a specific participating country): a. Known HIV-infected subjects unless on effective anti-retroviral therapy with an undetectable viral load within 6 months, or b. Known or suspected hepatitis B if active infection. Subjects with chronic hepatitis B infection must have an undetectable HBV viral load on suppressive therapy, if indicated; positive surface antibody alone is not an exclusion, or c. Known or suspected hepatitis C infection which has not been treated and cured unless currently on treatment with an undetectable viral load). 13. Uncontrolled or life-threatening diseases compromising safety evaluation. 14. Diagnosed or treated for another malignancy within 5 years before the first dose, or previously diagnosed with another malignancy and have any evidence of residual disease, including ductal carcinoma in situ of the breast. Subjects with non-melanoma skin cancer, other carcinoma in situ if have undergone complete resection or cervix carcinoma in situ are not excluded if they have undergone complete resection. Synchronous endometrial and prior diagnosis of endometrial cancer within 5 years is not excluded if all of the following conditions are met: Stage IA, superficial myometrial invasion, without lymphovascular invasion, and not poorly differentiated subtypes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Progression-free survival (PFS): To determine the efficacy by progression free survival (using investigator assessment of scans according to RECIST v1.1) of oregovomab compared to placebo when administered with chemotherapy (paclitaxel/carboplatin) to subjects with newly diagnosed ovarian cancer (FIGO Stage III or IV) who have undergone optimal debulking surgery;Secondary Objective: - To determine the efficacy by overall survival of oregovomab compared to placebo when administered with background chemotherapy (paclitaxel/carboplatin) to subjects with newly diagnosed ovarian cancer (FIGO Stage III or IV) who have undergone optimal debulking surgery - To assess the safety and tolerability of oregovomab compared to placebo when administered with background chemotherapy (paclitaxel/carboplatin) to subjects with newly diagnosed ovarian cancer (FIGO Stage III or IV) who have undergone optimal debulking surgery - To evaluate the effects of treatment with oregovomab compared to placebo when administered with background chemotherapy (paclitaxel/carboplatin) on Health-related Quality of Life (HRQoL) as assessed by trial outcome index (TOI) of the Functional Assessment of Cancer Therapy – Ovarian (FACT-O) and 3 additional questions from the NFOSI-18 in subjects with newly diagnosed ovarian cancer (FIGO Stage III or IV) who have undergone optimal debulking surgery;Primary end point(s): PFS, defined as date of randomization which occurs following surgery to the date of event defined as the first documented progression as per RECIST v1.1 as determined by the investigator or death due to any cause ;Timepoint(s) of evaluation of this end point: Date of disease progression as determined by the investigator (in conjunction with the local radiologist) or date of death. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - OS, defined as date of randomization to date of death due to any cause - Frequency/ severity of vital signs measurements, physical examination findings, changes in clinical laboratory parameters (hematology, biochemistry, urinalysis), and incidence of adverse events (AEs) – including AEs, serious AEs (SAEs), deaths, and AEs leading to discontinuation of treatment - Change from baseline in the global health status/QOL scale score of the Functional Assessment of Cancer Therapy-Ovary (FACT-O TOI) and 3 additional questions from the NFOSI-18 in each treatment group.;Timepoint(s) of evaluation of this end point: OS: Overall survival will be calculated from the date of randomization which occurs following primary or interval surgery prior to Cycle 1 in Cohort 1 – Primary Surgery and prior to Cycle 4 in Cohort 2 – NACT + Interval Surgery to the date of death. Subjects who are alive at the time of analysis of the primary endpoint, or who withdraw consent or are lost to follow-up, will be censored at the day they were last known to be alive. QOL scale score: Overall score, sub-scores, and individual items will be summarized and compared between treatment groups by cohort. The primary analysis will be based on overall score from baseline through month 36, with other measurements considered supportive. | — |
Countries
Argentina, Belgium, Brazil, Canada, Chile, Czech Republic, Hungary, India, Italy, Korea, Republic of, Mexico, Romania, Spain, Taiwan, United States
Contacts
Public ContactDr Sunil Gupta
CanariaBio Inc.
Outcome results
None listed