Determine if Either of 2 Doses of Study Drug Given With a Low-dose of Cyclophosphamide After a Complete or Partial Response to a Platinum-based Second-line Therapy in Women With Recurrent Ovarian Carcinoma Results in a Longer Time to Progression Whe

• Status: Withdrawn
• Trial end date: 2008-05-31
• Target enrollment: 0
• Participant gender: Female

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: EMD Serono
• Treatments: Cyclophosphamide

Criteria

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