Ovarian Cancer
Conditions
Keywords
Epithelial Cancer, Epithelial Carcinoma, Epithelial Ovarian Cancer, Epithelial Ovarian Carcinoma, Fallopian Tube Cancer, Fallopian Tube Carcinoma, Ovarian Cancer, Ovarian Carcinoma, Ovarian Epithelial Cancer, Ovarian Epithelial Carcinoma, Peritoneal Cancer, Peritoneal Carcinoma, Advanced Epithelial Ovarian Cancer
Brief summary
The purpose of this study is to determine whether the investigational drug catumaxomab delivered in the planned treatment schedule is a safe and effective treatment for women with advanced ovarian cancer who experience a complete response to chemotherapy.
Detailed description
A multi-center, phase II study of catumaxomab in ovarian cancer patients who experience a complete response to chemotherapy. Each eligible patient will receive four ascending doses of catumaxomab, administered intraperitoneally via an indwelling catheter or port. Catumaxomab will be administered as a 3-hour constant rate infusion with a dosing interval of 3-4 days. Each patient will participate in this study for up to 4 months (includes the baseline screening period, 11 to 21 days treatment period, and up to 90 days/3 months follow-up), with post-study follow-up every 3 months for 2 years. Catumaxomab is a trifunctional antibody targeting epithelial cell adhesion molecule (EpCAM) on tumor cells and CD3 (cluster of differentiation 3) on T cells. Trifunctional antibodies represent a new concept for targeted anticancer therapy. This new antibody class has the capability to redirect T cells and accessory cells (e.g. macrophages, dendritic cells \[DCs\] and natural killer \[NK\] cells) to the tumor site. According to preclinical data, trifunctional antibodies activate these different immune effector cells, which can trigger a complex anti-tumor immune response.
Interventions
DRUGcatumaxomab
Catumaxomab administered as four 3-hour, constant-rate, intraperitoneal (IP) infusions of 10, 20, 50, 150 microgram (mcg).
Sponsors
Fresenius Biotech North America
Neovii Biotech
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent form before any protocol-specific screening procedures * Histologically confirmed diagnosis of epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIb - IV * Optimal or sub-optimal cytoreductive surgery * Clinical complete response to platinum and taxane-based therapy consisting of at least four cycles, based on computed tomography (CT) scan and a CA-125 (cancer antigen 125) level below 35 U/mL * Age ≥18 years * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Last dose of platinum and taxane-based therapy completed within 6 weeks prior to the start of catumaxomab treatment * Negative serum pregnancy test result at screening in women of childbearing potential (applies to patients without documented menopause or sterility) * Willingness of patients of childbearing potential to use an effective contraceptive method (i.e. oral contraceptive, cervical cap, diaphragm with spermicide, condom with spermicide, or intrauterine device) during the study and for at least 6 months after the last infusion
Exclusion criteria
* Acute or chronic systemic infection * Exposure to chemotherapy, radiotherapy, immunotherapy or investigational anti-cancer therapy within 6 weeks of first dose of catumaxomab other than last regimen of platinum and taxane chemotherapy as outlined in protocol * Known human immunodeficiency virus (HIV) infection * Previous treatment with non-humanized murine (rat or mouse) monoclonal antibodies (mAb) * Inadequate renal function (creatinine \> 1.5 x upper limit of normal \[ULN\]) * Inadequate hepatic function: * Alanine aminotransferase (ALT) \> 2.5 x ULN or * Aspartate aminotransferase (AST) \> 2.5 x ULN or * Bilirubin \> 1.5 x ULN * Platelets \< 100,000 cells/mm\^3 * Absolute neutrophil count (ANC) \< 1,500 cells/mm\^3 * History of myocardial infarction, congestive heart failure or relevant cardiac arrhythmia within the last 6 months * No other malignancy within the past 5 years except non-melanoma skin cancer or carcinoma in situ of the cervix if adequately treated * No history of brain metastases * Any further condition or disease that would, in the opinion of the Investigator, expose the patient to undue risk
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Completed a 4-dose Series of Catumaxomab Infusions (Defined as 10-20-50-150 Micrograms) Within 21 Days | 21 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Negative (Undetectable) Humoral Immune Responses to Catumaxomab Therapy | 2 months | Humoral immune response of participants with functional immune system to catumaxomab can provide important information regarding why a therapy may work for some participants and not for others. An undetectable humoral response by itself does not necessarily imply lack of study drug activity. Humoral response is one of the possible selected measurements of the study drug activity at a time point in the study. |
| Number of Participants With no Residual Disease Prior to Catumaxomab Treatment Via 2nd-look Laparoscopy or Laparotomy (These Procedures Are Optional) | Baseline | — |
| Median Time of Progression-free Survival in Weeks (Post-study for 24 Months) | 2 years | — |
| Number of Participants Who Survived (Post-study at 24 Month Visit) | 2 years | Number of participants who survived (post-study at 24 month visit) is the number of participants who did not die |
| Number of Participants With no Residual Disease at 3 Months After Catumaxomab Treatment Via 3rd-look Laparoscopy or Laparotomy (These Procedures Are Optional) | 3 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Catumaxomab 4 dose series (10-20-50-150 micrograms) within 21 days | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Patient non-compliance | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Catumaxomab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants |
| Age Continuous | 56.6 years STANDARD_DEVIATION 9.36 |
| Region of Enrollment United States | 47 participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 47 |
| serious Total, serious adverse events | 19 / 47 |
Outcome results
Primary
Number of Participants Who Completed a 4-dose Series of Catumaxomab Infusions (Defined as 10-20-50-150 Micrograms) Within 21 Days
Time frame: 21 days
Population: Treated population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catumaxomab | Number of Participants Who Completed a 4-dose Series of Catumaxomab Infusions (Defined as 10-20-50-150 Micrograms) Within 21 Days | 29 Participants |
Secondary
Median Time of Progression-free Survival in Weeks (Post-study for 24 Months)
Time frame: 2 years
Population: Post study full analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Catumaxomab | Median Time of Progression-free Survival in Weeks (Post-study for 24 Months) | 86.1 weeks |
Secondary
Number of Participants Who Survived (Post-study at 24 Month Visit)
Number of participants who survived (post-study at 24 month visit) is the number of participants who did not die
Time frame: 2 years
Population: Post study full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catumaxomab | Number of Participants Who Survived (Post-study at 24 Month Visit) | 39 participants |
Secondary
Number of Participants With Negative (Undetectable) Humoral Immune Responses to Catumaxomab Therapy
Humoral immune response of participants with functional immune system to catumaxomab can provide important information regarding why a therapy may work for some participants and not for others. An undetectable humoral response by itself does not necessarily imply lack of study drug activity. Humoral response is one of the possible selected measurements of the study drug activity at a time point in the study.
Time frame: 2 months
Population: Full analysis population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catumaxomab | Number of Participants With Negative (Undetectable) Humoral Immune Responses to Catumaxomab Therapy | 41 Participants |
Secondary
Number of Participants With no Residual Disease at 3 Months After Catumaxomab Treatment Via 3rd-look Laparoscopy or Laparotomy (These Procedures Are Optional)
Time frame: 3 months
Population: Only 1 patient received 3rd-look laparoscopy/laparotomy as determined by the investigator and no residual disease was found.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catumaxomab | Number of Participants With no Residual Disease at 3 Months After Catumaxomab Treatment Via 3rd-look Laparoscopy or Laparotomy (These Procedures Are Optional) | 0 participants |
Secondary
Number of Participants With no Residual Disease Prior to Catumaxomab Treatment Via 2nd-look Laparoscopy or Laparotomy (These Procedures Are Optional)
Time frame: Baseline
Population: 2nd look laparoscopy/laparotomy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Catumaxomab | Number of Participants With no Residual Disease Prior to Catumaxomab Treatment Via 2nd-look Laparoscopy or Laparotomy (These Procedures Are Optional) | 7 Participants |