Oregovomab Plus Chemo in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer Following Optimal Debulking Surgery

Ovarian Cancer Clinical Trial

— FLORA-5  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04498117
• Other study ID #: QPT-ORE-005
• Secondary ID: GOG-3035FLORA-5F
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 25, 2020
• Est. completion date: August 26, 2027

Study information

• Verified date: December 2023
• Source: CanariaBio Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 615
• Est. completion date: August 26, 2027
• Est. primary completion date: September 26, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Drug:
• Paclitaxel
175 mg/m^2, every 3 weeks
• Carboplatin
AUC 6 IV Day 1 x 6 cycles (every 21 days)

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

Drug:
• Carboplatin
AUC 5-6 IV Day 1 x 6 cycles (every 21 days)

Locations

Country	Name	City	State
Argentina	CEMAIC - Centro Medico Privado	Córdoba	Cordoba
Argentina	Clínica Universitaria Privada Reina Fabiola	Córdoba	Cordoba
Argentina	Sanatorio de la Mujer	Rosario
Argentina	Sanatorio Parque S.A	Salta
Argentina	CER San Juan Centro Polivalente de Asistencia e Inv. Clinica	San Juan
Argentina	Clinicas Viedma S.A.	Viedma
Belgium	ZNA Middelheim	Antwerpen
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Clinique CHC MontLégia	Liège
Brazil	Centro de Pesquisas Clinica Reichow	Blumenau
Brazil	Oncosite - Centro de Pesquisa Clinica e Oncologia	Guimaraes
Brazil	Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa - Hospital Mae de Deus	Porto Alegre
Brazil	Fundação Doutor Amaral Carvalho	San Paolo
Brazil	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo André
Brazil	Clínica São Germano - Oncologia	Sao Paulo
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	City of Health Hospital at Laval (Cité de la Santé de Laval)	Laval	Quebec
Canada	CHUM Centre de Recherche (affiliated with University of Montreal)	Montréal	Quebec
Canada	McGill University Health Centre/Glen Site/ Royal Victoria Hospital	Montréal	Quebec
Canada	CHUS - Hôpital Fleurimont	Sherbrooke	Quebec
Chile	Centro de Investigación Clínica Bradford Hill	Santiago
Chile	Sociedad de Investigaciones Medicas Limitada	Temuco
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Kralovske Vinohrady	Prague
Czechia	Fakultni nemocnice Bulovka	Praha
Czechia	Fakultni nemocnice v Motole	Praha
Czechia	Vseobecna fakultni nemocnice v Praze	Praha
Hungary	Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet	Budapest
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest
Hungary	Debreceni Egyetem	Debrecen
Hungary	Bacs-Kiskun Megyei Oktatokorhaz	Kecskemét
Hungary	Zala Megyei Szent Rafael Korhaz	Zalaegerszeg
India	Fortis Hospital Ltd	Bangalore
India	Fortis Hospital Ltd	Bengaluru
India	All India Institute of Medical Services	Delhi
India	Max Super Specialty Hospital	Mohali
India	Sushrut Hospital	Mumbai
India	Fortis Hospital	Noida
India	Deenanath Mangeshkar Hospital	Pune
India	Ruby Hall Clinic	Pune
Italy	Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)	Monza
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome
Italy	Università Campus Bio-Medico di Roma	Rome
Korea, Republic of	National Cancer Center	Goyang
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Soeul
Mexico	Investigacion Onco Farmaceutica S. de R.L. de C.V. (OncoTech)	La Paz
Mexico	Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey
Mexico	Clinical Medical Research S.C.	Orizaba	Veracruz
Mexico	SMIQ S. de R.L. de C.V.	Querétaro
Mexico	Centro Potosino de Investigación Medica S.C.	San Luis Potosi
Spain	Hospital Clinic de Barcelona	Barcelona	Catalonia
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Catalonia
Spain	ICO l'Hospitalet-Hospital Duran i Reynals	L'Hospitalet De Llobregat
Spain	Instituto Valenciano de Oncologia IVO	Valencia
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei county	Taipei
United States	Womens Cancer Care Associates	Albany	New York
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	MultiCare Regional Cancer Center - Auburn	Auburn	Washington
United States	University of Colorado Health	Aurora	Colorado
United States	Texas Oncology, P.A. - Austin	Austin	Texas
United States	Tufts Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center PRIME	Bronx	New York
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	SCC at UH Geauga Medical Center	Chardon	Ohio
United States	University of Virginia Health Systems	Charlottesville	Virginia
United States	Cleveland Clinic	Cleveland	Ohio
United States	Cleveland Clinic Fairview Hospital	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	John Muir Health Clinical Research Center	Concord	California
United States	Minnesota Oncology Hematology - Mercy Hospital	Coon Rapids	Minnesota
United States	Women's Cancer Care/Mary Bird Perkins Cancer Center	Covington	Louisiana
United States	Texas Oncology, P.A.	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Minnesota Oncology Hematology	Edina	Minnesota
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Texas Oncology, P.A. - Fort Worth	Fort Worth	Texas
United States	MetroWest Medical Center	Framingham	Massachusetts
United States	MultiCare Regional Cancer Center-Gig Harbor Medical Park	Gig Harbor	Washington
United States	Kapiolani Medical Center for Women and Children/University of Hawaii	Honolulu	Hawaii
United States	The Queens Medical Center	Honolulu	Hawaii
United States	Memorial Herman Hospital	Houston	Texas
United States	Kaiser Permanente Southern California	Irvine	California
United States	Grandview Medical Center/Kettering Medical Center	Kettering	Ohio
United States	Moores UC San Diego Cancer Center	La Jolla	California
United States	Mount Sinai - PRIME	Lake Success	New York
United States	Sparrow Hospital	Lansing	Michigan
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Lowell General Hospital	Lowell	Massachusetts
United States	University of Wisconsin	Madison	Wisconsin
United States	University of Minnesota Health - Maple Grove Clinic	Maple Grove	Minnesota
United States	Cleveland Clinic Hillcrest Hospital	Mayfield Heights	Ohio
United States	Minnesota Oncology Hematology	Minneapolis	Minnesota
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Smilow Cancer Hospital	New Haven	Connecticut
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Mount Sinai The Blavatnik Family Chelsea Medical Center	New York	New York
United States	Virginia Oncology Associates - Hampton	Norfolk	Virginia
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	UH Minoff Health Center - Seidman	Orange Village	Ohio
United States	AdventHealth Orlando	Orlando	Florida
United States	The Valley Hospital (Valley Health)	Paramus	New Jersey
United States	Honor Health	Phoenix	Arizona
United States	Magee Women's Hospital of UPMC	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Center at UPMC Passavant	Pittsburgh	Pennsylvania
United States	Epic Care	Pleasant Hill	California
United States	Northwest Cancer Specialists, P.C.-Portland-Rose Quarter	Portland	Oregon
United States	Portsmouth Regional Hospital	Portsmouth	New Hampshire
United States	Women & Infants Hospital of Rhode Island	Providence	Rhode Island
United States	MultiCare Institute for Research and Innovation	Puyallup	Washington
United States	Duke Women's Cancer Care Raleigh	Raleigh	North Carolina
United States	VCU Massey Cancer Center	Richmond	Virginia
United States	Kaiser Permanente Riverside Medical Center	Riverside	California
United States	Carilion Clinic Gynecological Oncology	Roanoke	Virginia
United States	University of California, Davis Comprehensive Cancer Center	Sacramento	California
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Frauenshuh Cancer Center	Saint Louis Park	Minnesota
United States	Minnesota Oncology Hematology	Saint Paul	Minnesota
United States	Women's Cancer Florida/Women's Cancer Associates	Saint Petersburg	Florida
United States	Texas Oncology San Antonio Medical Center	San Antonio	Texas
United States	Lewis Cancer & Research Pavilion at St. Joseph's Candler	Savannah	Georgia
United States	Sanford Research/USD-Sioux Falls	Sioux Falls	South Dakota
United States	Tufts Medical Center Cancer Center in Stoneham	Stoneham	Massachusetts
United States	Stony Brook University Hospital	Stony Brook	New York
United States	MultiCare Regional Cancer Center - Tacoma	Tacoma	Washington
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	Oklahoma Cancer Specialist and Research Institution, LLC	Tulsa	Oklahoma
United States	Contra Costa Oncology	Walnut Creek	California
United States	John Muir Health Gynecologic Cancer Services	Walnut Creek	California
United States	SCC at St. John's Medical Center	Westlake	Ohio
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
CanariaBio Inc.	Gynecologic Oncology Group, Iqvia Pty Ltd

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  Hungary,  India,  Italy,  Korea, Republic of,  Mexico,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Efficacy by times to subsequent therapies and time to next progression	Tumor response measurement by iRECIST; Time to First Subsequent Therapy (TFST), defined as tie form the date of randomization to first subsequent anti-cancer therapy or death; Time to Second Subsequent Therapy, defined as time from the date of randomization to second anti-cancer therapy start date or death; Progression Free Survival 2, defined from the date of randomization to the first documented progression on next-line therapy or death.	Date of randomization, until date of subsequent therapy or death, or up to approximately 6 years
Other	Potential Biomarkers	Human Anti-Mouse Antibody (HAMA); HAMA interference-free CA-125; Neutrophil + Monocyte to Lymphocyte Ratio (NMLR); Phenotyping or immune subsets, including myeloid-derived suppressor cells (MDSC); Functional assessment of CD4+ and CD8+ T-cells with a focus on measuring the number and frequency of INF-y-producing CD8+ T-cells using flow cytometry	Date of randomization, until date of discontinuation, or up to approximately 6 years
Primary	Investigator Assessed Progression Free Survival	Date of randomization to radiographically-confirmed disease progression according to RECIST v1.1 as determined by the investigator or death	Date of randomization until date of first documented disease progression or date of death from any cause, whichever comes first, at up to approximately 6 years.
Secondary	Overall Survival	Date of randomization to the date of death	Date of randomization up until date of death from any cause, up to approximately 11 years
Secondary	Safety and Tolerability	Incidence of adverse events (AEs) leading to discontinuation of treatment, frequency/severity of vital signs measurements, physical examination findings, and changes in clinical laboratory parameters	Date of randomization up until date of discontinuation of treatment, date of significant physical examination changes, date of significant clinical changes, up to approximately 6 years
Secondary	Change in Quality of Life	Change from baseline in the global health status/QOL scale score of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O TOI); Three additional questions from the NFOSI-18 in each treatment group	Changes from baseline assessment, until date of discontinuation, or up to approximately 6 years