Efficacy Multicentre Trial of ImmunoTherapy Vaccination With Abagovomab to Treat Ovarian Cancer Patients

A Randomised,Double Blind, Placebo Controlled, Multicentre Trial of Abagovomab Maintenance Therapy in Patients With Epithelial Ovarian Cancer After Complete Response to First Line Chemotherapy

The purpose of this study is to evaluate the benefit of vaccination with Abagovomab, an experimental immunotherapy in ovarian cancer patients. The benefit will be evaluated in terms of time the remission status is kept as well as prolongation of life expectancy.

Standard initial treatment of ovarian cancer patients includes both surgery and chemotherapy which in the vast majority of cases achieves the disappearance of ovarian cancer lesions. This status, called "clinical remission" which means having no evidence of cancer on CT scan or physical examination needs to be carefully follow up in order to confirm the maintenance of the remission status or to early detect if the cancer grows again and then start a new chemotherapy. At present, no approved therapies exist for the maintenance treatment of patients who achieved the clinical remission.

This trial aims to evaluate if the repeated vaccination with Abagovomab creates an immunoresponse which is able to fight the cancer cells thus keeping the remission status as long as possible and help patients live disease-free and longer.

Patients who achieve the remission status after chemotherapy will be screened for study participation and if they meet the criteria for inclusion they will start to receive a single subcutaneous injection every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase). The duration of treatment is up to approximately 4 years or it will be stopped in case relapse occurs.

In order to evaluate the real benefit of vaccination, the experimental treatment includes Abagovomab (the active drug) or placebo (the vehicle only, without drug), with a double chance to receive Abagovomab. Assignment of Abagovomab or placebo will be done by a computerised system and nobody in the study will know which treatment has been allocated until study end.

Patients will be visited every 4 weeks and will undergo CT scan of pelvis and abdomen every 12 weeks in order to confirm the remission status or to early detect if relapse eventually occurs. This will be done in blind condition (i.e. without being aware which treatment the patient is going to receive) for the first part of the study which is expected to last four years. After then the overall status of patient will continue to be monitored by phone contact for additional five years.

Inclusion Criteria:

At a maximum of 12 weeks after the last cycle of first line standard platinum/taxane intravenous (IV) or intraperitoneal (IP) chemotherapy, patients must fulfill all the following inclusion criteria:

• Age >/= 18 years;

• Properly executed written informed consent;

• History of histological and CA125 (> 35 U/ml) confirmed diagnosis of stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer;

• History of debulking surgery and 6-8 cycles of standard platinum/taxane based non-investigational IV-IP chemotherapy;

• Complete clinical response defined as:

• Normal physical examination;

• No symptoms suggestive of persistent cancer;

• No definite evidence of disease by computed tomography (CT) of the abdomen and pelvis within the previous 4 weeks;

• Negative chest x-ray (or chest CT scan) within the previous 4 weeks;

• Serum CA125 within the normal laboratory range.

• Adequate hematologic, renal and hepatic function:

  • Absolute Neutrophil Count (ANC) >/=1.5 * 109/l;
  • Platelets >/= 75 * 109/l;
  • Haemoglobin >/= 6.2 mmol/l (>9.9 g/dl);
  • Serum creatinine </= 1.5 * ULN (Upper Limit of Normal);
  • Bilirubin </= 1.5 * ULN; AST, ALT, AP </= 2.5 * ULN.

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) </= 2.

Exclusion Criteria:

Patients are ineligible to participate in the study, if any of the following criteria are present:

• any other invasive malignancies, with the exception of non-melanoma skin cancer or cervical carcinoma in situ, within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy;
• known active autoimmune disease requiring chronic treatment with immunosuppressive agents (e.g., rheumatoid arthritis, ulcerative colitis, etc.);
• known immune deficiency (e.g. HIV, hypogammaglobulinemia, etc.);
• known infection with hepatitis B, or hepatitis C;
• history of recent myocardial infarction (</= 6 months) or decompensated heart failure (New York Heart Association - NYHA class >/= III);
• previous or concomitant use of any anti-cancer therapy other than the platinum-taxane based 1st line chemotherapy for ovarian cancer; any maintenance or consolidation therapy is not permitted after completion of standard front line chemotherapy.
• concomitant use of any other investigational agent;
• any prior investigational anti-cancer vaccine or monoclonal antibody;
• known allergy to murine proteins;
• any significant medical or psychiatric condition, drug or alcohol abuse that might prevent the patient from complying with all study procedures;
• clinically significant active infection;
• concomitant use of any immunosuppressive agent (e.g., steroids, cyclosporin, etc.);
• major surgery within the previous 2 weeks;
• radiotherapy within the previous 4 weeks;
• any significant toxicity from prior chemotherapy;
• unreliability or inability to follow protocol requirements;
• potentially childbearing and not willing to use adequate contraceptive methods throughout the entire study period;
• pregnancy.