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

Sponsor

CanariaBio Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05605535

Collaborator

Raptim Research Pvt. Ltd (Other)

Enrollment

Locations

Arms

41.1

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Neoplasm Epithelial Ovarian Cancer Fallopian Tube Neoplasms Peritoneal Carcinoma Ovarian Serous Adenocarcinoma	Biological: Oregovomab Drug: Paclitaxel Drug: Carboplatin Biological: Placebo	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

88 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Dec 12, 2022

Anticipated Primary Completion Date :

Sep 15, 2024

Anticipated Study Completion Date :

May 15, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination of Oregovomab and chemotherapy Six (6) cycles of chemotherapy with oregovomab given only at specific cycles (Cycle 1, Cycle 3, Cycle 4, Cycle 6 and Cycle 6 plus 12 weeks).	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 Names: MAb-B43.13 Drug: Paclitaxel 175 mg/m^2, every 3 weeks Other Names: Taxol Drug: Carboplatin AUC 5 or 6 IV Day 1 x 6 cycles (every 21 days) Other Names: Paraplatin
Placebo Comparator: Combination of Placebo and chemotherapy Six (6) cycles of chemotherapy with placebo given only at specific cycles (Cycle 1, Cycle 3, Cycle 4, Cycle 6 and Cycle 6 plus 12 weeks).	Drug: Paclitaxel 175 mg/m^2, every 3 weeks Other Names: Taxol Drug: Carboplatin AUC 5 or 6 IV Day 1 x 6 cycles (every 21 days) Other Names: 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

Arm

Intervention/Treatment

Experimental: Combination of Oregovomab and chemotherapy

Six (6) cycles of chemotherapy with oregovomab given only at specific cycles (Cycle 1, Cycle 3, Cycle 4, Cycle 6 and Cycle 6 plus 12 weeks).

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 Names:

MAb-B43.13

Drug: Paclitaxel

175 mg/m^2, every 3 weeks

Other Names:

Taxol

Drug: Carboplatin

AUC 5 or 6 IV Day 1 x 6 cycles (every 21 days)

Other Names:

Paraplatin

Placebo Comparator: Combination of Placebo and chemotherapy

Six (6) cycles of chemotherapy with placebo given only at specific cycles (Cycle 1, Cycle 3, Cycle 4, Cycle 6 and Cycle 6 plus 12 weeks).

Drug: Paclitaxel

175 mg/m^2, every 3 weeks

Other Names:

Taxol

Drug: Carboplatin

AUC 5 or 6 IV Day 1 x 6 cycles (every 21 days)

Other Names:

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

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) Rate at 12 months [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.

Secondary Outcome Measures

Overall Response Rate (ORR) [At 3 months]
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
Disease Control Rate (DCR): [At 3 months]
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
Response to Surgery [At 4 months]
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)
Progression Free Survival [Approximately up to 4 years]
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.
Overall Survival [Approximately up to 8 years]
Overall survival is defined as date of randomization to date of death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult females 18 years old or older.
Patients with newly diagnosed epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin FIGO Stage III or IV disease.
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.).
Suitable venous access for the study-required procedures.
Serum CA125 levels ≥ 50 U/mL prior to Cycle 1 of NACT chemotherapy + oregovomab or placebo.
Adequate bone marrow function:
Absolute neutrophil count (ANC) ≥ 1,500/μL.
Platelets ≥100,000/μL.
Hemoglobin ≥ 8.0 g/dL (Note: Blood transfusion is permitted up to 48 hours before the first dose of study treatment).
Adequate liver function:
Bilirubin < 1.5 times upper limit normal (ULN).
LDH, SGOT/AST and SGPT/ALT < 2.5 times ULN.
Adequate renal function:

Creatinine ≤ 1.5 times ULN.

ECOG Performance Status of 0, 1 or 2.
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.
Signed written informed consent form and authorization permitting release of personal health information. Ability to comply with treatment and follow up

Exclusion Criteria:

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).
Patients must not have received any prior chemotherapy, immunotherapy, targeted or hormonal therapy.
Patients who are lactating and breastfeeding or have a positive serum pregnancy test within 14 days prior to the first dose of study treatment.
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.
Active autoimmune disease such as rheumatoid arthritis, SLE, ulcerative colitis, Crohn's Disease, MS, or ankylosing spondylitis, requiring active disease modifying treatment.
Known allergy to murine proteins or hypersensitivity to any of the excipients of the oregovomab, paclitaxel, or carboplatin.
Chronically treated with immunosuppressive drugs such as cyclosporine, adrenocorticotropic hormone (ACTH), etc.
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.
Recognized acquired, hereditary, or congenital immunodeficiency disease, including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia.
Clinically significant active infection(s) at the time of screening.
Any of the following conditions (on-study testing is not required):
Known HIV-infected patients unless on effective anti-retroviral therapy with an undetectable viral load within 6 months, or
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
Known or suspected hepatitis C infection which has not been treated and cured unless currently on treatment with an undetectable viral load.
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.

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 III lesions

Contraindication to the use of pressor agents.
Undergone prior surgical debulking.
History or evidence upon physical examination of CNS disease, seizures not controlled with standard medical therapy, or any brain metastases.
Any of the following cardiovascular conditions:
Acute myocardial infarction within 6 months before the first dose of study treatment.
Current history of New York Heart Association (NYHA) Class III or IV heart failure.
Evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic clinically significant findings.
Unable to read or understand or unable to sign the necessary written consent before starting treatment.
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.

Contacts and Locations

Locations

	Site	City	State	Country
1	King George Hospital	Visakhapatnam	Andhra Pradesh	India
2	Omega Hospitals	Visakhapatnam	Andhra Pradesh	India
3	Himalaya Cancer Hospital and Research Institute	Vadodara	Gujarat	India
4	Kailash Cancer Hospital and Research Centre	Vadodara	Gujarat	India
5	Regional Cancer Centre, Medical College	Trivandrum	Kerala	India
6	Saveetha Medical College and Hospitals	Chennai	Tamilnadu	India
7	Sri Ramchandra Medical Centre	Chennai	Tamilnadu	India
8	Institute of Medical Sciences, BHU	Varanasi	Uttar Pradesh	India