Ovarian Cancer
Conditions
Keywords
Ovarian, Cancer, Epithelial, Recurrent, Platinum, Second-line therapy, Maintenance Therapy, Biologic, Targeted Therapy, Antibody
Brief summary
The purpose of this study is to determine if either of two doses of EMD 273066 when given with a low dose of cyclophosphamide will result in a second time to progression that is as long or longer than the first time to progression
Interventions
DRUGTucotuzumab celmoleukin (EMD 273066)
Sponsors
EMD Serono
Study design
Allocation
RANDOMIZED
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 written informed consent * Age 18 years or older * Have histologically documented ovarian carcinoma (including primary peritoneal carcinoma) * Have archival tumor tissue available for EpCAM expression determination by immunohistochemistry * Received first-line platinum-based chemotherapy of up to 8 cycles (approximately 15 to 24 weeks) * Experienced a complete response to first-line platinum-based chemotherapy * Experienced a platinum-free interval of at least 6 but not more than 24 months starting at the end of the last cycle of first-line chemotherapy until recurrence * Treatment with Avastin (bevacizumab) is permitted during first-line platinum-based chemotherapy through TTP and platinum-based reinduction therapy up to 28 days prior to start of EMD 273066 * Experienced a partial or complete response after up to 8 cycles of second-line platinum-based chemotherapy * Have a CT/MRI scan within 4 weeks prior to starting treatment * Be able to start cyclophosphamide and EMD 273066 treatment within 3 to 5 weeks of completion of second-line chemotherapy * KPS ≥70% * No clinical history of significantly impaired renal function or chronic kidney disease. Must have an estimated glomerular filtration rate ≥50 mL/min determined by the Cockgroft-Gault-formula * WBC count ≥2.5x10³/µL (or total granulocytes ≥1x10³/µL) * Absolute lymphocyte count (ALC) ≥0.5x103/µL * Platelet count ≥100,000/µL * Hemoglobin (Hgb) level ≥9 g/dl * ALT and AST ≤2.5xULN, total bilirubin \<1.5xULN * Serum sodium, potassium and phosphorus within normal limits * Serum amylase within normal limits * Serologic testing within 4 weeks prior to starting study treatment with negative results for hepatitis C virus (HCV), human immunodeficiency virus (HIV) and hepatitis B virus (HBV) demonstrated by negative hepatitis B core antibody (HBc Ab) and hepatitis B surface antigen (HbsAg) * Negative pregnancy test and willingness to use effective contraception for the study duration and 1 month thereafter if of procreative potential
Exclusion criteria
* Dyspnea at rest, exercise intolerance * In any subject with clinically significant non-malignant pulmonary disease: Pulmonary function testing (to include Forced Vital Capacity \[FVC\] and 1-second Forced Expiratory Volume \[FEV-1\]) showing \<70% of predicted values for FVC or FEV-1 and/or DLCO \<50%. * In any subject with pulmonary or pleural metastatic disease: Arterial oxygen saturation at rest measured transcutaneously on room air \< 90% or increased risk for respiratory compromise related to IL2 exposure in the judgment of the investigator. * ECG with evidence of clinically significant disease within 4 weeks prior to starting study treatment * Cardiac stress test (e.g., exercise or pharmacological thallium test; exercise or pharmacological echocardiography) with abnormal results within 4 weeks prior to starting treatment in subjects who have a history of coronary heart disease (myocardial infarction, angina pectoris or pathologic coronary angiography) * Any current evidence of congestive heart failure with NY Heart Association Grade 2 through 4 or echocardiogram with a left ventricular ejection fraction \<45% or other signs of clinical significant heart disease * History of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other clinically significant arrhythmias * Evidence of active brain metastases * Previous malignancy other than ovarian cancer in the last 5 years except basal cell cancer of the skin or pre-invasive cancer of the cervix * Pregnant or lactating female * An immediate need for palliative radiotherapy or systemic corticosteroid therapy * Significant active infection * Major surgery, chemotherapy, or radiation within 21 days of starting study treatment * Received another experimental drug within 28 days of starting study treatment * Uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥100 mmHg) or hypotension (systolic ≤90 mmHg) * Presence of medically significant third space fluids such as pleural or pericardial effusions or edema of toxicity grade ≥2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 \[17\]. * Exception allowed for disease-related peritoneal ascites unless patient requires frequent and repetitive paracentesis management. Previous diagnosis of an autoimmune disease involving a major organ system * Transplant recipient on immunosuppressive therapy * Acute esophageal or gastroduodenal ulcers * History of prior therapy or a serious uncontrolled medical disorder that in the Investigator's opinion would impair participation in the study
Outcome results
None listed