A Controlled Study of the Effectiveness of Oregovomab (Antibody) Plus Chemotherapy in Advanced Ovarian Cancer

NCT01616303CompletedPHASE2INTERVENTIONAL

Summary

This is a Phase 2 randomized study with two treatment arms to compare the effectiveness of oregovomab (a murine monoclonal antibody directed against cancer antigen 125 (CA125)) when combined with first-line chemotherapy (carboplatin and paclitaxel) to first-line chemotherapy (carboplatin and paclitaxel alone) in female patients with advanced ovarian cancer.

Key Facts

Lead Sponsor

Quest PharmaTech Inc.

Enrollment

97

Start Date

2012-06-15

Completion Date

2015-06-15

Study Type

INTERVENTIONAL

Official Title

Phase 2: A Randomized Controlled Study on Effectiveness of Chemotherapy (Carboplatin-Paclitaxel) Versus Chemo-immunotherapy (Carboplatin-Paclitaxel-Oregovomab) in Patients With Advanced Epithelial Ovarian, Adnexal or Peritoneal Carcinoma

Interventions

CarboplatinPaclitaxeloregovomab

Conditions

Ovarian Neoplasms

Eligibility

Age Range

18 Years – 75 Years

Sex

FEMALE

Inclusion Criteria:

* have newly diagnosed epithelial adenocarcinoma of ovarian, tubal or peritoneal origin and French Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) Stage III/IV disease.
* have preoperative CA125 levels \> 50 U/mL
* have optimal cytoreduction (RT\<1)
* be anticipated to have first-line chemotherapy infusion within 6 weeks after surgery
* be available to complete the protocol for the duration of the study
* have adequate Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1,500/µL, equivalent to Common Terminology Criteria (CTCAE v3.0) grade 1. Platelets greater than or equal to 100,000/µL; hemoglobin greater than or equal to 8.0 g/dL
* have adequate Renal function: creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v3.0 grade 1
* have adequate Hepatic function: bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1). SGOT and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1)
* able to sign informed consent and provide authorization permitting release of personal health information
* have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Exclusion Criteria:

* have an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis)
* have a known allergy to murine proteins or have had a documented anaphylactic reaction to any drug, or cannot tolerate cyclophosphamide
* are being chronically treated with immunosuppressive drugs such as cyclosporin, adrenocorticotropic hormone (ACTH), or systemic corticosteroids.
* have a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia
* have an acquired, hereditary, or congenital immunodeficiency
* have uncontrolled diseases other than cancer
* have contraindications to the use of pressor agents
* have undergone more than one surgical debulking
* have hepatic dysfunction, eg, bilirubin more than 1.5 times higher than normal levels, lactate dehydrogenase (LDH), serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) doubled compared to normal or albumin \<3.5 g/dL
* have severe renal insufficiency with serum creatinine \>1.6 mg/dL
* have concomitant diseases or treatments that may confound the results of the study, which may preclude the completion of the protocol or may mask adverse reactions
* are to be tested with other medications during treatment
* are unable to read or understand or unable to sign the necessary written consent before starting treatment

Outcome Measures

Primary Outcomes

CA125 ELISPOT assay response for cytotoxic T cell antigen specific immunity induction to end of first-line chemotherapy

Change from baseline CA125 ELISPOT assay after stimulation with oregovomab (MAb-B43.13 against CA125) measured at approximately 12 weeks and 25 weeks after the start of first-line chemotherapy

Time frame: At Baseline (up to 4 weeks before Cycle 1), at Cycle 5 (approximately 12 weeks after Cycle 1) and termination (approximately 25 weeks after Cycle 1)

Secondary Outcomes

Time to clinical relapse

The time period from the date of randomization to the date of confirmed relapse as defined by clinical, radiologic, and/or pathologic evaluations.

Time frame: Up to three years after treatment in the study

Immune parameters: HAMA (human anti-mouse antibody) titers and DTH (delayed type hypersensitivity)

Laboratory test for human anti-mouse antibody (HAMA) present in patients' sera. DTH (delayed type hypersensitivity) is an on-site test conducted by the investigator by injecting a small amount of the Oregovomab product and three other antigens (mumps, tetanus, and Candida) into the skin of the patient and observing the effects.

Time frame: Up to three years after treatment in the study

Clinical response

Patients will be categorized into one of the following: increasing disease, stable disease, or progression \[measurable disease studies\]

Time frame: Up to three years after treatment in the study

Overall Survival

The observed length of life from entry into the study to death or the date of last contact

Time frame: Up to three years after treatment in the study

Locations

University of Connecticut Health Center, Farmington, United States

Northern Indiana Cancer Research Consortium, South Bend, United States

Linked Diseases

Ovarian Neoplasms

Ovarian Neoplasms — a type of gynecological cancer.

Linked Papers

2020-01-06

Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study

This randomized phase II study tested the hypothesis that schedule dependent chemo-immunotherapy with oregovomab improves progression free survival (PFS) and overall survival (OS) in optimally resected, Stage III/IV ovarian cancer. Patients from both academic centers and private practice in the US and Italy with Stage III/IV optimally cytoreduced ovarian cancer were randomized to standard six cycle IV carboplatin-paclitaxel chemotherapy (CP) versus CP plus four immunizations with oregovomab (CPO). A translational assessment of a cellular immune response was the primary endpoint; PFS and OS were measured as secondary endpoints. 97 patients at thirteen centers were accrued to the protocol, 47 to CPO and 50 to CP. Technical issues led to inconsistent performance of the primary CA125 ELISPOT leading to unevaluable results. At a median follow up of 42 months, PFS and OS outcomes revealed an unexpectedly large treatment effect for CPO relative to CP alone, with median PFS of 41.8 months (95% C.I.: 21.8 - N.E.) for CPO and 12.2 months (10.4-18.6) for CP (p = 0.0027, HR 0.46, CI 0.28-0.7). For OS, the median for CPO has not yet been reached (NE) (45.2-NE) and for CP was 43.2 months (31.8-NE) (p = 0.043, HR 0.35, CI 0.16-0.74). The oregovomab treatment resulted in no change in toxicity profile from CP. The previously identified potential clinical benefit of IV CP when administered with oregovomab was further refined in this randomized phase II study. Increases of PFS and OS of statistically and clinically significant magnitude were evident in this study of a front line chemo-immunotherapy treatment of ovarian cancer.

2020-01-03

Translational immune correlates of indirect antibody immunization in a randomized phase II study using scheduled combination therapy with carboplatin/paclitaxel plus oregovomab in ovarian cancer patients

The standard-of-care (SOC) first-line therapy for ovarian cancer (OC) patients is plagued with high relapse rates. Several studies indicated the immune system's prominent role changing the disease course in OC patients. Chemo-immunotherapy regimens, currently being explored, include oregovomab, which is a monoclonal antibody specific for the OC associated antigen carbohydrate/cancer antigen 125 (CA125) that yielded promising results when administered together with SOC in a previous study. The QPT-ORE-002 multi-site phase II randomized study demonstrated that in patients with advanced OC, oregovomab combined with first-line SOC improved overall and progression-free survival, compared to SOC alone. The study included an Italian cohort in which we demonstrated that adding oregovomab to SOC resulted in increased patient numbers with amplified CA125-specific CD8

Linked Investigators

Alessandra Battaglia