Oregovomab Plus Chemotherapy in Neo-adjuvant Setting in Newly Diagnosed Patients With Advanced Epithelial Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

A Phase 2, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial Comparing Chemoimmunotherapy (Paclitaxel-Carboplatin-Oregovomab) Versus Chemotherapy (Paclitaxel-Carboplatin-Placebo) as Neoadjuvant Therapy in Patients With Advanced Epithelial Ovarian, Fallopian Tube or Peritoneal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05605535
• Other study ID #: QPT-ORE-006
• Status: Recruiting
• Phase: Phase 2
• Start date: February 7, 2023
• Est. completion date: May 15, 2026

Study information

• Verified date: August 2023
• Source: CanariaBio Inc.
• Contact: Clinical Operations
• Phone: 1-780-448-1400
• Email: ClinicalTrialDisclosures[@]oncoquestinc.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A clinical study to compare the efficacy and safety of five administrations of oregovomab versus placebo, infused in schedule dependent sequence with specific cycles of a standard six-cycle chemotherapy regimen (paclitaxel and carboplatin), for the treatment of patients with newly diagnosed advanced ovarian cancer who are planned to receive neoadjuvant treatment followed by interval debulking surgery (IDS) and adjuvant treatment.

Description:

Phase 2, double-blind, placebo-controlled, multi-center study to compare the efficacy and safety of five administrations of oregovomab 2 mg IV versus placebo, infused in a schedule dependent sequence with specific cycles of a standard six-cycle chemotherapy regimen (paclitaxel and carboplatin), for the treatment of patients with newly diagnosed advanced ovarian cancer who are planned to receive neoadjuvant treatment. Patients will receive oregovomab or placebo at Cycles 1 and 3 in combination with paclitaxel and carboplatin prior to IDS, followed by oregovomab or placebo at Cycles 4 and 6 in combination with paclitaxel and carboplatin, and oregovomab or placebo monotherapy at Cycle 6 plus 12 weeks.

This study will screen approximately 96 patients to randomize approximately 88 patients. All eligible patients will be stratified by FIGO Stage (Stages IIIA, IIIB versus Stages IIIC, IV).

The study includes screening period, treatment period, post-treatment follow up, safety follow and long term follow up.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: May 15, 2026
• Est. primary completion date: September 15, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult females 18 years old or older.

2. Newly diagnosed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin FIGO Stage III or IV patients whose disease is confirmed based on biopsy sample.

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. Suitable venous access for the study-required procedures.

5. Serum CA125 levels = 50 U/mL prior to Cycle 1 of NACT chemotherapy + oregovomab or placebo.

6. Adequate bone marrow function:

1. Absolute neutrophil count (ANC) = 1,500/µL.

2. Platelets =100,000/µL.

3. Hemoglobin = 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before the first dose of study treatment).

7. Adequate liver function:

1. Bilirubin < 1.5 times upper limit normal (ULN).

2. SGOT/AST and SGPT/ALT < 2.5 times ULN.

8. Adequate renal function:

a. Creatinine = 1.5 times ULN.

9. ECOG Performance Status of 0, 1 or 2.

10. 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 6 months after last dose of study treatment.

11. Signed written informed consent form and authorization permitting release of personal health information. Ability to comply with treatment and follow up

Exclusion Criteria:

1. Patients with mucinous adenocarcinoma, carcinosarcoma, tumors with neuroendocrine features and low-grade adenocarcinoma (including low grade serous and FIGO grade 1 endometrioid adenocarcinomas of the ovary).

2. FIGO Stage IV patients:

1. FIGO stage IV patients suspected or diagnosed with bone or brain metastasis are excluded.

2. FIGO stage IV patients diagnosed with lung and/or liver metastasis with tumour size more than 2 cm are excluded.

3. FIGO stage IV patients diagnosed with lung and/or liver metastasis and expected to administer with more than 3 cycles of chemotherapy and/or not suitable for interval debulking surgery are excluded.

3. Patients must not have received any prior chemotherapy, immunotherapy, targeted or hormonal therapy.

4. Patients who are lactating and breastfeeding or have a positive serum pregnancy test within 14 days prior to the first dose of study treatment.

5. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study treatment according to this protocol.

6. Active autoimmune disease such as rheumatoid arthritis, 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, except for 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):

1. Known HIV-infected patients unless on effective anti-retroviral therapy with an undetectable viral load within 6 months prior to randomization, or

2. 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

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. 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. Patients with non-melanoma skin cancer, ductal carcinoma in-situ (DCIS) of the breast or cervix carcinoma in situ are not excluded if they have undergone complete resection. a. 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, and not poorly differentiated subtypes including papillary serous, clear cell or other FIGO Grade II and III lesions.

15. Contraindication to the use of pressor agents. 16. Undergone prior surgical debulking.

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:

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. 19. Unable to read or understand or unable to sign the necessary written consent before starting treatment. 20. 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. 21. Patients who will receive Hyperthermic Intraperitoneal Chemotherapy (HIPEC), any other anti-cancer medications, including bevacizumab, PARPi, or any other investigational agent(s) with 3 cycles of paclitaxel and carboplatin neo-adjuvant treatment will be excluded.

Related Conditions & MeSH terms

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

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 5 or 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

Locations

Country	Name	City	State
India	KLES Dr. Prabhakar Kore Hospital and Medical Research Centre	Belgaum	Karnataka
India	Saveetha Medical College and Hospitals	Chennai	Tamilnadu
India	Sri Ramchandra Medical Centre	Chennai	Tamilnadu
India	MNJ Cancer Hospital	Hyderabad	Telangana
India	Sri Ram Cancer Hospital	Jaipur	Rajasthan
India	Amrita Institute of Medical Sciences	Kochi	Kerala
India	N.R.S. Medical College And Hospital	Kolkata	West Bengal
India	King Georges Medical University	Lucknow	Uttar Pradesh
India	JIPMER	Pondicherry
India	Regional Cancer Centre, Medical College	Trivandrum	Kerala
India	Himalaya Cancer Hospital and Research Institute	Vadodara	Gujarat
India	Kailash Cancer Hospital and Research Centre	Vadodara	Gujarat
India	Institute of Medical Sciences, BHU	Varanasi	Uttar Pradesh
India	King George Hospital	Visakhapatnam	Andhra Pradesh
India	Omega Hospitals	Visakhapatnam	Andhra Pradesh
India	Acharya Vinoba Bhave Rural Hospital Wardha	Wardha	Maharashtra

Sponsors (2)

Lead Sponsor	Collaborator
CanariaBio Inc.	Raptim Research Pvt. Ltd

Country where clinical trial is conducted

India, 

References & Publications (3)

Berek J, Taylor P, McGuire W, Smith LM, Schultes B, Nicodemus CF. Oregovomab maintenance monoimmunotherapy does not improve outcomes in advanced ovarian cancer. J Clin Oncol. 2009 Jan 20;27(3):418-25. doi: 10.1200/JCO.2008.17.8400. Epub 2008 Dec 15. — View Citation

Braly P, Nicodemus CF, Chu C, Collins Y, Edwards R, Gordon A, McGuire W, Schoonmaker C, Whiteside T, Smith LM, Method M. The Immune adjuvant properties of front-line carboplatin-paclitaxel: a randomized phase 2 study of alternative schedules of intravenous oregovomab chemoimmunotherapy in advanced ovarian cancer. J Immunother. 2009 Jan;32(1):54-65. doi: 10.1097/CJI.0b013e31818b3dad. — View Citation

Brewer M, Angioli R, Scambia G, Lorusso D, Terranova C, Panici PB, Raspagliesi F, Scollo P, Plotti F, Ferrandina G, Salutari V, Ricci C, Braly P, Holloway R, Method M, Madiyalakan M, Bayever E, Nicodemus C. Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study. Gynecol Oncol. 2020 Mar;156(3):523-529. doi: 10.1016/j.ygyno.2019.12.024. Epub 2020 Jan 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) Rate at 12 months	PFS, is assessed from date of randomization to the date of first documented progression as per RECIST v1.1 as determined by the investigator or death due to any cause.	At 12 months
Secondary	Overall Response Rate (ORR)	Overall response rate is defined according to RECIST v1.1 measured at end of first 3 cycles of study treatment and prior to debulking surgery treatment: Complete response; Partial Response	At 3 months
Secondary	Disease Control Rate (DCR):	Disease control rate is defined according to RECIST v1.1 measured at end of first 3 cycles of treatment and prior to debulking surgery treatment: Complete response; Partial Response; Stable Disease	At 3 months
Secondary	Response to Surgery	Upon completion of neo-adjuvant treatment and IDS, Response to surgery will be assessed on the size of residual disease - none (R0), < 1 cm (R1), = 1 cm (R2)	At 4 months
Secondary	Progression Free Survival	Progression free survival is defined as date of randomization to date of first documented progression as per RECIST v1.1 as determined by the investigator or death due to any cause and OS defined as date of randomization to date of death due to any cause.	Approximately up to 4 years
Secondary	Overall Survival	Overall survival is defined as date of randomization to date of death due to any cause.	Approximately up to 8 years