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Oregovomab Plus Chemo in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer Following Optimal Debulking Surgery (FLORA-5)

C

CanariaBio

Status and phase

Active, not recruiting
Phase 3

Conditions

Ovarian Neoplasms
Fallopian Tube Adenocarcinoma
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Peritoneal Cancer
Fallopian Tube Serous Adenocarcinoma
Ovarian Cancer
Peritoneal Carcinoma
Ovarian Serous Adenocarcinoma

Treatments

Drug: Paclitaxel
Biological: Placebo
Drug: Carboplatin
Biological: Oregovomab

Study type

Interventional

Funder types

NETWORK
Industry

Identifiers

NCT04498117
GOG-3035 (Other Identifier)
QPT-ORE-005
FLORA-5 (Other Identifier)
FLORA5 (Other Identifier)

Details and patient eligibility

About

Study 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.

Full description

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, approximately 372 subjects randomized in a 1:1 ratio (i.e., chemotherapy with oregovomab or chemotherapy with placebo). For Cohort 2 - NACT + Interval Surgery, approximately 230 subjects will be randomized in a 1:1 ratio (i.e., chemotherapy with oregovomab or chemotherapy and placebo).

Enrollment

615 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Adults 18 years old or older.

  2. Newly diagnosed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin FIGO Stage III or IV disease.

  3. 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). Debulking surgery must be optimal, R1 or R0 (defined as R1, macroscopic less than 1 cm in diameter, or R0, microscopic or no evidence of tumor). Assessment of debulking surgery will be determined at the time of the surgical procedure, not by post-surgical imaging.

    1. For Cohort 1, subject will undergo primary debulking surgery. Subject must receive initial dose of paclitaxel 175 mg/m^2 given intravenously and carboplatin AUC 6 IV every 3 weeks 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 after primary debulking surgery
    2. For Cohort 2, subject will undergo interval debulking surgery (IDS). Prior to IDS, subjects must have receive 3 cycles of paclitaxel and carboplatin as neoadjuvant treatment. After IDS, subjects must receive paclitaxel 175 mg/m^2 IV and carboplatin AUC 5-6 IV every 3 weeks, starting cycle 4. Cycle 4 of chemotherapy ± oregovomab/placebo must be anticipated to occur within 6 weeks after IDS.
  5. Suitable venous access for the study-required procedures

  6. Preoperative serum CA-125 levels ≥ 50 U/mL for Cohort 1, serum CA-125 levels ≥ 50 U/mL prior to first neoadjuvant chemotherapy for Cohort 2.

  7. Adequate bone marrow function:

    1. Absolute neutrophil count (ANC) ≥ 1,500/µL
    2. 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:

    1. Bilirubin < 1.5 times upper limit normal (ULN)
    2. Lactate Dehydrogenase (LDH), SGOT/AST and SGPT/ALT < 2.5 times ULN
  10. Adequate renal function:

    a. Creatinine ≤ 1.5 times ULN

  11. ECOG Performance Status of 0 or 1.

  12. For women of childbearing potential, must be willing to avoid pregnancy by using highly effective method of contraception from the first dose of study treatment to 6 months after last dose of study treatment as defined per protocol. Belgium and South Korea only: Use of a highly effective method of contraception from 28 days before first dose.

  13. Signed informed consent and authorization permitting release of personal health information.

  14. Willingness and ability to complete patient quality of life questionnaires.

Exclusion criteria

  1. BRCA1 or BRCA2 germline gene mutation test result with:

    1. Pathogenic, ambiguous or inconclusive result available within 28 days prior to starting study treatment (subjects with BRCA1 or BRCA 2 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
    2. 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, multiple sclerosis (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):

    1. Known HIV-infected subjects unless on effective anti-retroviral therapy with an undetectable viral load within 6 months, or
    2. 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
    3. 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 including papillary serous, clear cell lesions.

  15. Contraindications to the use of pressor agents.

  16. Undergone more than one surgical debulking or have not recovered from surgery.

  17. Anticipated treatment with any other anti-cancer medications, including bevacizumab, PARP inhibitors, or any investigational agent(s) during the study.

  18. History or evidence upon physical examination of CNS disease, seizures not controlled with standard medical therapy, or any brain metastases.

  19. Any of the following cardiovascular conditions:

    1. Acute myocardial infarction within 6 months before the first dose of study treatment.
    2. Current history of New York Heart Association (NYHA) Class III or IV heart failure.
    3. Evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic clinically significant findings.
  20. Unable to read or understand or unable to sign the necessary written consent before starting treatment.

  21. May not receive any live, attenuated vaccine administered within 28 days (or 4 weeks) prior to enrollment, during the study, and for at least 90 days after the last dose of study treatment.

  22. Subjects who receive Hyperthermic Intraperitoneal Chemotherapy (HIPEC), any other anti-cancer medications, including bevacizumab, PARP inhibitors, or any other investigational agent(s) with 3 cycles of paclitaxel and carboplatin neoadjuvant treatment prior to IDS.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

615 participants in 4 patient groups, including a placebo group

Cohort 1- Surgery Active
Experimental group
Description:
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).
Treatment:
Biological: Oregovomab
Drug: Carboplatin
Drug: Paclitaxel
Drug: Carboplatin
Cohort 1 - Primary Surgery Control
Placebo Comparator group
Description:
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).
Treatment:
Drug: Carboplatin
Drug: Paclitaxel
Drug: Carboplatin
Biological: Placebo
Cohort 2 - NACT + Interval Surgery Active
Experimental group
Description:
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).
Treatment:
Biological: Oregovomab
Drug: Carboplatin
Drug: Paclitaxel
Drug: Carboplatin
Cohort 2 - NACT + Interval Surgery Control
Placebo Comparator group
Description:
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).
Treatment:
Drug: Carboplatin
Drug: Paclitaxel
Drug: Carboplatin
Biological: Placebo

Trial contacts and locations

149

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Central trial contact

Clinical Operations

Data sourced from clinicaltrials.gov

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