| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| advanced epithelial ovarian, fallopian tube or peritoneal carcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| ovarian and associated cancers |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
- 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 |
|
| E.2.2 | Secondary objectives of the trial |
- 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. Cycle 1 of chemotherapy ± oregovomab/placebo must be anticipated to occur within 6 weeks after primary debulking surgery, and
ii. The primary debulking surgery is optimal, R1 or R0 (defined as R1, macroscopic no greater than 1 cm in diameter, or R0, microscopic or no evidence of tumor).
b. For subjects who will undergo interval debulking surgery (Cohort 2 – NACT/Interval Surgery):
i. Subject must have received neoadjuvant treatment with 3 cycles of paclitaxel 175 mg/m2 IV over 3 hours every approximately 3 weeks (21 Days), followed by carboplatin area under the curve (AUC) 5-6 administered intravenously (IV) approximately every 3 weeks (21 Days), and
ii. 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 no greater than 1 cm in diameter, or R0, microscopic or no evidence of tumor).
5. Suitable venous access for the study-required procedures.
6. Cohort 1 – Primary Surgery: Preoperative serum CA-125 levels ≥ 50 U/mL, or in Cohort 2 – NACT + Interval Surgery: serum CA-125 levels ≥ 50 U/mL prior to first pre-operative chemotherapy.
7. Adequate bone marrow function:
a. Absolute neutrophil count (ANC) ≥ 1,500/μL
b. Platelets ≥ 100,000/μL
c. Hemoglobin ≥ 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before first dose of study treatment).
8. Adequate liver function:
a. Bilirubin < 1.5 times upper limit normal (ULN)
b. Lactate Dehydrogenase (LDH), SGOT/AST and SGPT/ALT < 2.5 times ULN
c. Albumin >3.5 g/dL
9. Adequate renal function:
a. Creatinine ≤ 1.5 times ULN
10. ECOG Performance Status of 0 or 1.
11. For women of childbearing potential, must be willing to avoid pregnancy by using a highly effective method of contraception from the first dose of study treatment to 60 days after last dose of study treatment. Adequate contraception is defined in Section 8.2.5.
12. Sign informed consent and authorization permitting release of personal health information.
13. Willingness and ability to complete patient quality of life questionnaires. |
|
| E.4 | Principal exclusion criteria |
1. BRCA1 or BRCA2 germline gene mutation test result with:
a. Positive, ambiguous or inconclusive result available within 28 days prior to starting study treatment, or
b. Known BRCA1 and BRCA2 somatic mutations, and known positive germline, or
c. Somatic Homologous Recombination Deficiency (HRD) who will receive PARP inhibitor front-line maintenance therapy.
2. Subjects with mucinous adenocarcinoma and low-grade adenocarcinoma.
3. 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).
4. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
5. 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.
6. Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab, paclitaxel, or carboplatin.
7. Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc. (see Appendix G).
8. 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.)
9. Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia.
10. Clinically significant active infection(s) at the time of screening.
11. Any of the following conditions (on-study testing is not required):
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 (patients 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).
12. Uncontrolled or life-threatening diseases compromising safety evaluation.
13. 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. Subjects with non-melanoma skin cancer or cervix carcinoma in situ are not excluded if they have undergone complete resection. Synchronous endometrial cancer, but a 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, grade 3 or not poorly differentiated subtypes including papillary serous, clear cell or other FIGO Grade 3 lesions.
14. Contraindications to the use of pressor agents.
15. Undergone more than one surgical debulking or have not recovered from surgery.
16. Anticipated treatment with any other anti-cancer medications, including bevacizumab, poly (ADP-ribose) polymerase (PARP) inhibitors, or any investigational agent(s) during the study.
17. History or evidence upon physical examination of CNS disease, seizures not controlled with standard medical therapy, or any brain metastases.
18. Any of the following cardiovascular conditions:
a. Acute myocardial infarction within 6 months before the first dose of study treatment.
b. Current history of New York Heart Association (NYHA) Class III or IV heart failure (see Appendix H).
c. Evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic clinically significant findings.
19. Unable to read or understand or unable to sign the necessary written consent before starting treatment. |
|
| E.5 End points |
| E.5.1 | 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 |
|
| E.5.1.1 | 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. |
|
| E.5.2 | 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. |
|
| E.5.2.1 | 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. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 44 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Brazil |
| Canada |
| Chile |
| China |
| Korea, Republic of |
| Mexico |
| Taiwan |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of study overall is defined as five years after the date of the last follow-up visit of the last subject who entered the follow-up period, or at sponsor’s decision to end the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
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