As \< 10% of the necessary patients required by the protocol were recruited and the data were not intended to support a labeling claim, it was determined that the abbreviated clinical study report (CSR) was the appropriate reporting format. No efficacy analyses were performed as the trial was terminated early with incomplete enrollment of \< 10%. The purpose of this study is to determine if an investigational cell therapy called Cvac can help epithelial ovarian cancer (EOC) from returning when administered to patients who are in complete remission after surgical removal of their tumor followed by standard first-line (Part A) or second-line (Part B) chemotherapy. Following remission, patients will undergo leukapheresis for the manufacture of the study agent. After completion of chemotherapy and confirmation of remission, patients will enter the treatment phase of the study.
This study proposes a nontoxic immunotherapeutic approach to extend overall survival in patients in complete remission. Most patients with ovarian cancer achieve complete clinical remission after optimal debulking surgery and first-line platinum-based chemotherapy. However, most patients, despite high response rates to first-line treatment, will relapse and undergo subsequent chemotherapy. Generally, the progression-free interval between treatments becomes shorter with each relapse, and the patient eventually dies of the disease. For production of Cvac, each patient's cells were enriched using cell separation techniques. The patient's cells were cultured for 5 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in AIM V® serum-free tissue culture medium (Thermo Fisher Scientific) to cultivate the growth of dendritic cells (DC). The culture was pulsed overnight with the antigen (mannosylated mucin 1 fusion protein \[M-FP\]) to arm the DCs to the specific mucin 1 antigen. After harvesting, the M-FP-pulsed DCs were formulated as a finished product (Cvac) in 1 mL aliquots, diluted in 5% human serum albumin (HSA) and 10% dimethyl sulfoxide (DMSO) at an approximate concentration of 60 × 10\^6 viable DCs/mL. The vials were cryopreserved and stored in the vapor phase of liquid nitrogen at the manufacturing facility. Different participants were enrolled in the 2 parts of the study. Part A To be eligible for participation, patients were diagnosed with stage III or IV epithelial ovarian cancer, underwent optimal debulking surgery (≤ 1 cm of residual disease), underwent platinum and taxane chemotherapy, with or without bevacizumab, and had a tumor that overexpressed mucin 1, as well as met all other study inclusion and exclusion criteria at screening. Patients who met all study inclusion and exclusion criteria were randomized in a 1:1 double-blinded fashion to either the Cvac (active) group or the placebo (control) group. After randomization, patients underwent mononuclear cell (MNC) collection for production of the study agent and then began first-line chemotherapy. After completion of chemotherapy and confirmation of complete clinical and radiological remission (Baseline), patients were entered into the treatment phase of the study. A total of 76 patients were recruited and randomized at centers in Europe, North America, and Australia. Part B To be eligible for participation, patients had first-line platinum-based chemotherapy with a complete response lasting for at least 6 months prior to relapse and achieved second remission following standard platinum-based second-line chemotherapy with or without a second bulk-reducing surgery, and had a tumor that over-expressed mucin 1, as well as met all other study inclusion and exclusion criteria. Patients who met all study inclusion and exclusion criteria were randomized in a 1:1 fashion to either the Cvac (active) group or the observational standard of care (control) group. After randomization, only patients randomized to Cvac underwent MNC collection for production of the study agent. After confirmation of no evidence of disease at the Baseline visit, patients were entered into the treatment phase of the study. A total of 15 patients were recruited and randomized at centers in Europe.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
91
Injections were done at 4 anatomical sites, 1 injection in each of the upper portions of both arms and both thighs.
Injections were done at 4 anatomical sites, 1 injection in each of the upper portions of both arms and both thighs. Placebo consisted of the Cvac formulation buffer (5% HSA, 10% DMSO) with 0.9% simethicone provided in 1 mL vials that had been cryopreserved and stored at the manufacturing facility.
LAC-USC Medical Center
Los Angeles, California, United States
Collaborative Research Group
Boynton Beach, Florida, United States
Sarasota Memorial Hospital
Sarasota, Florida, United States
University Gynecologic Oncology
Atlanta, Georgia, United States
Women's Cancer Center
Morristown, New Jersey, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Greenslopes Private Hospital
Greenslopes, Australia
Royal Brisbane and Women's Hospital
Herston, Australia
Part A - Overall Survival
Overall survival was defined as the number of days from Baseline to the date of death from any cause.
Time frame: Baseline to the end of the study (up to 3 years, 2 months)
Part A - Time to Next Treatment
Time to next treatment was defined as the number of days from Baseline to the date when the next treatment for epithelial ovarian cancer was started.
Time frame: Baseline to the end of the study (up to 3 years, 2 months)
Part A - Progression-free Survival
Progression-free survival was defined as the number of days from Baseline and the documented disease progression as defined by response evaluation criteria in solid tumors (RECIST) or death, whichever occurred earlier. Disease progression was defined as any measurable new lesion(s) that were accurately measured in at least 1 dimension. Any new lesion(s) with a minimum size of 20 mm were deemed as unequivocal (ie, clear or definite) progression. Any new lesion(s) with a minimum size of 15 mm but smaller than 20 mm were considered equivocal progression and had to be confirmed by a follow-up radiological procedure.
Time frame: Baseline to the end of the study (up to 3 years, 2 months)
Part B - Overall Survival
Overall survival was defined as the number of days from Baseline to the date of death from any cause.
Time frame: Baseline to the end of the study (up to 3 years, 2 months)
Part B - Time to Next Treatment
Time to next treatment was defined as the number of days from Baseline to the date when the next treatment for epithelial ovarian cancer was started.
Time frame: Baseline to the end of the study (up to 3 years, 2 months)
Part B - Progression-free Survival
Progression-free survival was defined as the number of days from Baseline and the documented disease progression as defined by response evaluation criteria in solid tumors (RECIST) or death, whichever occurred earlier. Disease progression was defined as any measurable new lesion(s) that were accurately measured in at least 1 dimension. Any new lesion(s) with a minimum size of 20 mm were deemed as unequivocal (ie, clear or definite) progression. Any new lesion(s) with a minimum size of 15 mm but smaller than 20 mm were considered equivocal progression and had to be confirmed by a follow-up radiological procedure.
Time frame: Baseline to the end of the study (up to 3 years, 2 months)
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