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

• ClinicalTrials.gov Identifier: NCT01616303
• Recruitment Status: Completed
• First Posted: June 11, 2012
• Last Update Posted: September 14, 2020
• Sponsor: Quest PharmaTech Inc.
• Information provided by (Responsible Party): Quest PharmaTech Inc.

Tracking Information

• First Submitted Date: May 30, 2012
• First Posted Date: June 11, 2012
• Last Update Posted Date: September 14, 2020
• Actual Study Start Date: June 15, 2012
• Actual Primary Completion Date: June 15, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 12, 2018)

CA125 ELISPOT assay response for cytotoxic T cell antigen specific immunity induction to end 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) ]

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

• Original Primary Outcome Measures (submitted: June 7, 2012): Change in CA125 ELISPOT assay response for cytotoxic T cell antigen specific immunity induction to end of first-line chemotherapy [ Time Frame: At Baseline (up to 4 weeks before Cycle 1), Cycle 5 (approximately 12 weeks after Cycle 1) and termination (approxmately 25 weeks after Cycle 1) ]

Current Secondary Outcome Measures (submitted: October 12, 2018)

• Time to clinical relapse [ Time Frame: Up to three years after treatment in the study ]
  The time period from the date of randomization to the date of confirmed relapse as defined by clinical, radiologic, and/or pathologic evaluations.
• Immune parameters: HAMA (human anti-mouse antibody) titers and DTH (delayed type hypersensitivity) [ Time Frame: Up to three years after treatment in the study ]
  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.
• Clinical response [ Time Frame: Up to three years after treatment in the study ]
  Patients will be categorized into one of the following: increasing disease, stable disease, or progression [measurable disease studies]
• Overall Survival [ Time Frame: Up to three years after treatment in the study ]
  The observed length of life from entry into the study to death or the date of last contact

Original Secondary Outcome Measures (submitted: June 7, 2012)

• Time to clinical relapse [ Time Frame: Study termination (approxmiately 25 weeks after Cycle 1) ]
  The time period from the date of randomization to the date of confirmed relapse as defined by clinical, radiologic, and/or pathologic evaluations.
• Immune parameters: HAMA (human anti-mouse antibody) titers and DTH (delayed type hypersensitivity) [ Time Frame: HAMA: screening, Cycle 3 (approx. 6 weeks after Cycle 1), Cycle 5 (approx. 12 weeks after Cycle 1), Cycle 5 plus 12 weeks (approx. 24 weeks after Cycle 1) DTH: screening and termination (approx. 25 weeks after Cycle 1) ]
  Laboratory test for (HAMA) human anti-mouse antibody 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.
• Clinical response [ Time Frame: Up to three years after enrollment in the study ]
  Patients will be categorized into one of the following: increasing disease, stable disease, or progression [measurable disease studies]
• Survival [ Time Frame: Up to three years after enrollment in the study ]
  The observed length of life from entry into the study to death or the date of last contact
• Change in vital signs from baseline to end of study [ Time Frame: At Baseline (up to 4 weeks before Cycle 1), Cycle 3 (approximately 6 weeks after Cycle 1), Cycle 5 (approximately 12 weeks after Cycle 1) and Cycle 5 plus 12 weeks (approxmately 24 weeks after Cycle 1) ]
  The following vital signs will be obtained: heart rate, respiratory rate, blood pressure, temperature
• Change in clinical laboratory results from baseline to end of chemotherapy [ Time Frame: At Baseline (up to 4 weeks before Cycle 1), Cycle 3 (approximately 6 weeks after Cycle 1), Cycle 5 (approximately 12 weeks after Cycle 1), Cycle 5 plus 12 weeks (approxmately 24 weeks after Cycle 1) and termination (approximately 25 weeks after Cycle 1) ]
  The following clinical laboratory results will be obtained: hematology (White Blood Cells [total count and differential], hemoglobin, hematocrit, Red Blood Cells), biochemistry (albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin [total], lactate dehydrogenase, protein, creatinine, urea, bicarbonate, chloride, potassium, sodium, calcium, phosphate, glucose, uric acid) and urinalysis (dipstick, pH, specific gravity, bilirubin, blood, protein, glucose, ketones, urobilinogen, microscopic evaluation)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Controlled Study of the Effectiveness of Oregovomab (Antibody) Plus Chemotherapy in Advanced Ovarian Cancer
• 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
• Brief 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.

Detailed Description

Oregovomab is an investigational drug previously used in clinical trials as an immunotherapeutic treatment of ovarian cancer patients whose tumor cells express the tumor associated antigen, CA125. The active component of oregovomab is the activated murine monoclonal antibody B43.13, an immunoglobulin G1k (IgG1k) subclass immunoglobulin that binds with high affinity (1.16E10/M) to CA125.

CA125 is a surface glycoprotein antigen that is expressed on more than 80% of all non-mucinous epithelial ovarian carcinomas where it occurs at elevated levels in the serum of patients with ovarian cancer. Little is known about its biological function. CA125 is associated with a large molecular weight mucin-like glycoprotein complex of 200-250 kilodaltons (kDa) and its genetic structure has recently been elucidated. There is good evidence to suggest that CA125 is a relevant target antigen for antigen-mediated immunotherapy of ovarian cancer.

The study will 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Ovarian Neoplasms

Intervention

• Drug: Carboplatin
  carboplatin (area under the curve (AUC) 6, administered intravenously in a single day for 6 cycles every three weeks [21 days])
• Drug: Paclitaxel
  Paclitaxel (175 mg / square meter, intravenously over three hours in one day to be repeated for 6 cycles every three weeks [21 days])
• Biological: oregovomab
  oregovomab (2 mg infused intravenously jointly during the 1st, 3rd and 5th chemotherapy cycle and 12 weeks after the 5th cycle).
  Other Name: OvaRex

Study Arms

• Active Comparator: carboplatin & paclitaxel
  first-line chemotherapy for ovarian cancer
  Interventions:

  • Drug: Carboplatin
  • Drug: Paclitaxel
• Experimental: carboplatin & paclitaxel & oregovomab
  first-line chemotherapy for ovarian cancer plus oregovomab
  Interventions:

  • Drug: Carboplatin
  • Drug: Paclitaxel
  • Biological: oregovomab

Publications *

• 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.
• Battaglia A, Buzzonetti A, Fossati M, Scambia G, Fattorossi A, Madiyalakan MR, Mahnke YD, Nicodemus C. 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. Cancer Immunol Immunother. 2020 Mar;69(3):383-397. doi: 10.1007/s00262-019-02456-z. Epub 2020 Jan 3. Erratum In: Cancer Immunol Immunother. 2020 Jul;69(7):1389.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 29, 2016): 97
• Original Estimated Enrollment (submitted: June 7, 2012): 80
• Actual Study Completion Date: October 12, 2018
• Actual Primary Completion Date: June 15, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01616303
• Other Study ID Numbers: QPT-ORE-002; 2010-024305-13 ( EudraCT Number )
• Has Data Monitoring Committee: No

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: Quest PharmaTech Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Quest PharmaTech Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Thomas Woo, M.Sc.; Quest PharmaTech Inc.
• Study Chair: Christopher Nicodemus, MD FACP; AIT Strategies

• PRS Account: Quest PharmaTech Inc.
• Verification Date: September 2020