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

December 22, 2020 updated by: Baxalta now part of Shire

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Georgia Regents University
    • Maryland
      • Silver Spring, Maryland, United States, 20910
        • Women's Health Specialists
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Stephenson Cancer Center at the University of Oklahoma
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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:
  • Macrophage Migration Inhibitory Factor Antibody (Anti-MIF)
  • Imalumab

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
4 weeks
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.
4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
4 weeks
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.
Up to 4 weeks
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
Baseline, weekly during the treatment period, and every 2 weeks during the safety follow-up period, up to approximately 6 months)
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
Throughout the study period of approximately 22 months
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
Throughout the study period of approximately 22 months
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
Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
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
Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
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
Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
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
Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
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
Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
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
Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
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.
Weekly from the baseline visit to the last week of safety follow-up (8 weeks or longer, if additional treatment will be implemented)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Baxalta now part of Shire

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 2, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 26, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 26, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 24, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 3, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 12, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 22, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 391402
  • 2015-003492-29 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the low number of study participants).

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Conditions

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