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 When Compared to the First Time to Progression.

An Open-label Phase II Study of Two Dose Levels of EMD 273066 Administered With Low-dose Cyclophosphamide Following Objective Response to Second-line Chemotherapy in Women With Recurrent Ovarian Carcinoma

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

Study Overview

• Status: Withdrawn
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Tucotuzumab celmoleukin (EMD 273066)

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tucotuzumab celmoleukin (EMD 273066)	Drug: Tucotuzumab celmoleukin (EMD 273066)

Collaborators and Investigators

• Sponsor: EMD Serono

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2006
• Primary Completion (Actual): May 31, 2008
• Study Completion (Actual): May 31, 2008

Study Registration Dates

• First Submitted: December 6, 2006
• First Submitted That Met QC Criteria: December 7, 2006
• First Posted (Estimate): December 8, 2006

Study Record Updates

• Last Update Posted (Actual): August 18, 2017
• Last Update Submitted That Met QC Criteria: August 15, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Cancer; Antibody; Biologic; Platinum; Recurrent; Epithelial; Ovarian; Maintenance Therapy; Targeted Therapy; Second-line therapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: EMR 62206-016