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

• ClinicalTrials.gov Identifier: NCT04498117
• Recruitment Status: Recruiting
• First Posted: August 4, 2020
• Last Update Posted: March 28, 2023
• Sponsor: CanariaBio Inc.
• Collaborators: Gynecologic Oncology Group; Iqvia Pty Ltd
• Information provided by (Responsible Party): CanariaBio Inc.

Tracking Information

• First Submitted Date: July 28, 2020
• First Posted Date: August 4, 2020
• Last Update Posted Date: March 28, 2023
• Actual Study Start Date: August 25, 2020
• Estimated Primary Completion Date: June 26, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 4, 2020)

Investigator Assessed Progression Free Survival [ Time Frame: Date of randomization until date of first documented disease progression or date of death from any cause, whichever comes first, at up to approximately 4 years. ]

Date of randomization to radiographically-confirmed disease progression according to RECIST v1.1 as determined by the investigator or death

Original Primary Outcome Measures (submitted: July 30, 2020)

Investigator Assessed Progression Free Survival [ Time Frame: Date of randomization up until date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to approximately 4 years. ]

Date of randomization to radiographically-confirmed disease progression according to RECIST v1.1 as determined by the investigator or death

Current Secondary Outcome Measures (submitted: August 4, 2020)

Overall Survival [ Time Frame: Date of randomization up until date of death from any cause, up to approximately 8 years ]

Date of randomization to the date of death Date of randomization to the date of death Date of randomization to the date of death

Original Secondary Outcome Measures (submitted: July 30, 2020)

Overall Survival [ Time Frame: Date of randomization up until date of death from any cause, whichever comes first, assessed up to approximately 8 years ]

Date of randomization to the date of death Date of randomization to the date of death Date of randomization to the date of death

Current Other Pre-specified Outcome Measures (submitted: August 4, 2020)

• Functional Assessment of Cancer Therapy-Ovarian Trial Outcome Index (FACT-O TOI) [ Time Frame: • Change from baseline in the global health status/QOL scale score of the FACT-O TOI, up to 4 years. ]
  Physical component of quality of life (QOL) measured by a modified Functional Assessment of Cancer Therapy-Ovarian Trial Outcome Index (FACT-O-TOI).
• NFOSI-18 [ Time Frame: Change from baseline in the NFOSI-18, assessed up to 4 years. ]
  Physical component of quality of life (QOL) will be measured using the FACT/NCCN Ovarian Symptom Index (FOSI).

Original Other Pre-specified Outcome Measures (submitted: July 30, 2020)

• Functional Assessment of Cancer Therapy-Ovarian Trial Outcome Index (FACT-O TOI) [ Time Frame: • Change from baseline in the global health status/QOL scale score of the Functional Assessment of Cancer Therapy-Ovary (FACT-O TOI) in each treatment group, assessed up to 4 years. ]
  Physical component of quality of life (QOL) will be measured using a modified Functional Assessment of Cancer Therapy-Ovarian Trial Outcome Index (FACT-O-TOI).
• NFOSI-18 [ Time Frame: Change from baseline in the NFOSI-18 in each treatment group, assessed up to 4 years. ]
  Physical component of quality of life (QOL) will be measured using the FACT/NCCN Ovarian Symptom Index (FOSI).

Descriptive Information

• Brief Title: Oregovomab Plus Chemo in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer Following Optimal Debulking Surgery
• Official Title: 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
• Brief Summary: 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.

Detailed 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, 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).

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

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

Intervention

• Biological: Oregovomab
  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
  Other Name: MAb-B43.13
• Drug: Paclitaxel
  175 mg/m^2, every 3 weeks
  Other Name: Taxol
• Drug: Carboplatin
  AUC 6 IV Day 1 x 6 cycles (every 21 days)
  Other Name: Paraplatin
• Biological: 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

Study Arms

• Experimental: Cohort 1- Surgery Active
  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).
  Interventions:

  • Biological: Oregovomab
  • Drug: Paclitaxel
  • Drug: Carboplatin
• Placebo Comparator: Cohort 1 - Primary Surgery Control
  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).
  Interventions:

  • Drug: Paclitaxel
  • Drug: Carboplatin
  • Biological: Placebo
• Experimental: Cohort 2 - NACT + Interval Surgery Active
  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).
  Interventions:

  • Biological: Oregovomab
  • Drug: Paclitaxel
  • Drug: Carboplatin
• Placebo Comparator: Cohort 2 - NACT + Interval Surgery Control
  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).
  Interventions:

  • Drug: Paclitaxel
  • Drug: Carboplatin
  • Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 30, 2020): 602
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 26, 2027
• Estimated Primary Completion Date: June 26, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Major 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 no greater than 1 cm in diameter, or R0, microscopic or no evidence of tumor).
5. Preoperative serum CA- 125 levels ≥ 50 U/mL.

6. Adequate bone marrow function:

   1. Absolute neutrophil count (ANC) greater than or equal to 1,500/µL
   2. Platelets greater than or equal to100,000/µL
   3. 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).

7. 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
   3. Albumin >3.5 g/dL

8. Adequate renal function:

   a. Creatinine less than or equal to1.5 times ULN

9. ECOG Performance Status of 0 or 1.

Major Exclusion Criteria:

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

   1. Positive, ambiguous or inconclusive result available within 28 days prior to starting study treatment, or
   2. Known BRCA1 and BRCA2 somatic mutations, and known positive germline, or
   3. 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. 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.
5. Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab, paclitaxel, or carboplatin.
6. Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc. (see Appendix G).
7. 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.)
8. Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia.
9. Anticipated treatment with any other anti-cancer medications, including bevacizumab, poly (ADP- ribose) polymerase (PARP) inhibitors, or any investigational agent(s) during the study.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Operations; 1-780-448-1400; ClinicalTrialDisclosures@oncoquestinc.com

• Listed Location Countries: Argentina, Belgium, Brazil, Canada, Chile, Czechia, Hungary, India, Italy, Korea, Republic of, Mexico, Poland, Romania, Spain, Taiwan, United States
• Removed Location Countries: China

Administrative Information

• NCT Number: NCT04498117
• Other Study ID Numbers: QPT-ORE-005; GOG-3035 ( Other Identifier: Gynecologic Oncology Group ); FLORA-5 ( Other Identifier: OncoQuest Pharmaceuticals Inc. ); FLORA5 ( Other Identifier: OncoQuest Pharmaceuticals Inc. )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: CanariaBio Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: CanariaBio Inc.
• Original Study Sponsor: Same as current

Collaborators

• Gynecologic Oncology Group
• Iqvia Pty Ltd

Investigators

• Study Director: Sunil Gupta, MD, FRCPC; CanariaBio Inc.

• PRS Account: CanariaBio Inc.
• Verification Date: March 2023