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Phase 1/2a Two-Arm Dose-Escalation Study of BAX69 in Subjects With Malignant Ascites of Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02540356
Recruitment Status : Terminated
First Posted : September 3, 2015
Results First Posted : June 15, 2017
Last Update Posted : May 15, 2019
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Brief Summary:
The purpose of this study is to evaluate the safety and tolerability of BAX69 monotherapy given either as intraperitoneal (IP) infusion (Single-Route Arm); or as IP infusion after intravenous (IV) infusion (IV+IP) (Double-Route Arm), and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for each Arm separately, in subjects with refractory ovarian cancer and recurrent malignant ascites. In both Arms, the plasma pharmacokinetics (PK) of BAX69 will be characterized, and pharmacodynamics (PD) markers will be explored in plasma and ascites. Two expansion cohorts will further assess the tolerability of the RP2D and explore clinical signs of efficacy.

Condition or disease Intervention/treatment Phase
Refractory Ovarian Cancer With Recurrent Symptomatic Malignant Ascites Biological: BAX69 Single-Route Arm Biological: BAX69 Double-Route Arm Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a, Open-Label, Parallel, Two-Arm Dose-Escalation Study to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of BAX69 in Subjects With Refractory Ovarian Cancer With Malignant Ascites
Actual Study Start Date : November 2, 2015
Actual Primary Completion Date : May 26, 2016
Actual Study Completion Date : May 26, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer

Arm Intervention/treatment
Experimental: Single-Route Arm
BAX69 administered weekly by intraperitoneal (IP) infusion only
Biological: BAX69 Single-Route Arm
Intraperitoneal (IP) only
Other Names:
  • Macrophage Migration Inhibitory Factor Antibody (Anti-MIF)
  • Imalumab

Experimental: Double-Route Arm
BAX69 administered weekly by intravenous (IV) infusion + intraperitoneal (IP) infusion
Biological: BAX69 Double-Route Arm
Intravenous (IV) infusion + intraperitoneal (IP) infusion
Other Names:
  • Imalumab
  • Macrophage Migration Inhibitory Factor Antibody (Anti-MIF)

Primary Outcome Measures :
  1. The Occurrence of Dose-limiting Toxicity (DLT) [ Time Frame: 4 weeks ]

    DLT is defined as any drug related treatment-emergent adverse event that occurs during the 28-day period after the first dose of Imalumab and that meets any of these criteria:

    • Any ≥ grade 3 non-hematologic toxicity assessed by the investigator as related to study drug (except: single lab value out of normal range not necessarily translating or considered a feature of clinical diagnosis requiring an intervention per investigator's interpretation and resolves to ≤ Grade 2 with adequate measure in 7 days; Transient grade 3 elevations of hepatic transaminases in the absence of simultaneous increase in serum bilirubin; Alopecia)
    • Any toxicity resulted in dose delay for ≥14 days
    • Any grade 4 hematologic toxicity (except lymphopenia)
    • Grade 3 febrile neutropenia
    • Grade 3 thrombocytopenia associated with bleeding
    • Any life-threatening complication/abnormality not covered in the NCICTCAE v4.03

  2. The Ratio of Puncture Free Survival (PuFS) Over Puncture-free Interval at Baseline [ Time Frame: 4 weeks ]

    PuFS is defined as the time from the last dose of Imalumab to the first therapeutic paracentesis after that, or death, whichever occurs first.

    Puncture-free interval at baseline is calculated as the time between the last 2 therapeutic paracenteses immediately before the first dose of Imalubmab.

Secondary Outcome Measures :
  1. Ratio of Time to First Paracentesis Post-treatment Over Puncture-free Interval at Baseline [ Time Frame: 4 weeks ]
    Time to first paracentesis post-treatment is calculated as the time between the last dose of Imalumab to subsequent first therapeutic paracentesis.

  2. Change in Ascites Volume Per Unit Time With Treatment [ Time Frame: Up to 4 weeks ]
    The volume of ascites from the last dose of Imalumab to the first post-treatment paracentesis per unit time will be compared to the volume of the last pre-treatment paracentesis per unit time. At each paracentesis, the volume of fluid that can be removed safely (measured by ultrasound-guided paracentesis) to achieve close to dryness should be withdrawn, measured, and documented.

  3. Changes in Ascites-related Symptoms [ Time Frame: Baseline, weekly during the treatment period, and every 2 weeks during the safety follow-up period, up to approximately 6 months) ]
    Ascites related symptoms: anorexia, nausea, early satiety, vomiting, abdominal pain, abdominal swelling, dyspnea, fatigue, swollen ankles, heartburn

  4. Occurrence of Serious Adverse Events (SAEs) and/or Treatment-emergent Adverse Events (TEAEs), Regardless of Causality or Relationship to Study Drug [ Time Frame: Throughout the study period of approximately 22 months ]
  5. Occurrence of Binding and/or Neutralizing Anti-imalumab (BAX69) Antibodies Following Treatment With Imalumab (BAX69) [ Time Frame: Throughout the study period of approximately 22 months ]
  6. Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) [ Time Frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours ]
  7. Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Minimum Observed Concentration (Cmin) [ Time Frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours ]
  8. Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Area Under the Concentration vs Time Curve (AUC) [ Time Frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours ]
  9. Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Half-life (t1/2) [ Time Frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours ]
  10. Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Apparent Systemic Clearance (CL) [ Time Frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours ]
  11. Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Volume of Distribution (V) [ Time Frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours ]
  12. Quality of Life (QoL) Measure - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Questionnaire [ Time Frame: Weekly from the baseline visit to the last week of safety follow-up (8 weeks or longer, if additional treatment will be implemented) ]
    QoL will be assessed using EORTC QLQ-C30.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Provision of a signed informed consent
  2. Female participants of non-childbearing potential, ≥18 years of age
  3. Anticipated life expectancy >3 months at the time of screening
  4. Metastatic ovarian epithelial cancer that are platinum-resistant, and has no better option available in the investigator's opinion
  5. Recurrent symptomatic malignant ascites having required at least 2 paracenteses within a 45-day interval prior to baseline paracentesis
  6. Participants who have an indwelling draining IP catheter (to be drained only under medical supervision)
  7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2
  8. Adequate hematological function, defined as:

    • Platelet count ≥100,000/μL
    • Prothrombin time (PT) and activated partial thromboplastin time (aPTT) <1.5 times the upper limit of normal (ULN)
    • Absolute neutrophil count ≥1,000/μL
    • Hemoglobin ≥9 g/dL, without the need for transfusion in the 2 weeks prior to screening
  9. Adequate renal function, defined as serum creatinine ≤2.0 times ULN and creatinine clearance >50 mL/min or estimated glomerular filtration rate (eGFR) >50 mL/min/1.73 m^2
  10. Adequate liver function, defined as:

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times ULN for participants without liver metastases, or ≤5 times ULN in the presence of liver metastases
    • Bilirubin ≤2.0 times ULN, unless participant has known Gilbert's syndrome
  11. Adequate venous access
  12. Participant is willing and able to comply with the requirements of the protocol

Exclusion Criteria:

  1. Known central nervous system metastasis that is unstable within the last 2 months
  2. Prior malignancy within the past 3 years, with the exception of curatively treated basal or squamous cell carcinoma of the skin, ductal carcinoma in situ of breast, in situ cervical carcinoma, and superficial bladder cancer
  3. Residual AEs >Grade 2 from previous treatment
  4. Myocardial infarction within 6 months prior to C1D1 treatment, and/or prior diagnoses of congestive heart failure (New York Heart Association Class III or IV), unstable angina, unstable cardiac arrhythmia requiring medication; and/or the participant is at risk for polymorphic ventricular tachycardia (eg, hypokalemia, family history or long QT syndrome)
  5. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg confirmed upon repeated measures
  6. Left ventricular ejection fraction <50% as determined by echocardiogram (ECHO) performed at screening or within 30 days prior to C1D1
  7. QT/QTc interval >480 msec, before C1D1 treatment administration, as determined by screening electrocardiogram (ECG)
  8. Received anti-tumor therapy (chemotherapy, investigational product, radiotherapy, retinoid therapy, or hormonal therapy) within 2 weeks (less than 14 days) prior to C1D1 with no residual toxicity >Grade 1; antibody therapy, molecular targeted therapy within 5 half-lives prior to C1D1
  9. Major surgery within 4 weeks (less than 28 days) prior to C1D1
  10. Active joint inflammation or other immune disorder involving joints (osteoarthritis is not exclusionary)
  11. Active infection involving IV antibiotics within 2 weeks prior to C1D1
  12. Positive serology test for hepatitis B virus (HBV), hepatitis C virus (HCV), or active tuberculosis
  13. Positive serology test for human immunodeficiency virus (HIV) type 1 and 2, or known history of other immunodeficiency disease
  14. Participant has received a live vaccine within 2 weeks (less than 14 days) prior to C1D1
  15. Known hypersensitivity to any component of recombinant protein production by Chinese Hamster Ovary (CHO) cells
  16. Any disorder or disease, or clinically significant abnormality on laboratory or other clinical test(s) (eg, blood tests and ECG), that in medical judgment of the investigator may impede the participant's participation in the study, pose increased risk to the participant, and/or confound the results of the study
  17. Participant is a family member or employee of the investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02540356

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United States, Florida
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
United States, Georgia
Georgia Regents University
Augusta, Georgia, United States, 30912
United States, Maryland
Women's Health Specialists
Silver Spring, Maryland, United States, 20910
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461
United States, Oklahoma
Stephenson Cancer Center at The University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baxalta now part of Shire
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Study Director: Study Director Shire

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Responsible Party: Baxalta now part of Shire Identifier: NCT02540356     History of Changes
Other Study ID Numbers: 391402
2015-003492-29 ( EudraCT Number )
First Posted: September 3, 2015    Key Record Dates
Results First Posted: June 15, 2017
Last Update Posted: May 15, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the website. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Pathologic Processes
Immunologic Factors
Physiological Effects of Drugs