Refractory Ovarian Cancer With Recurrent Symptomatic Malignant AscitesPhase 1/2NCT02540356
Phase 1/2a Two-Arm Dose-Escalation Study of BAX69 in Subjects With Malignant Ascites of Ovarian Cancer
A Phase 1/2 study testing BAX69 Single-Route Arm and BAX69 Double-Route Arm in people with Refractory Ovarian Cancer With Recurrent Symptomatic Malignant Ascites, run by Baxalta now part of Shire at 6 sites in United States.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Refractory Ovarian Cancer With Recurrent Symptomatic Malignant Ascites
- What is being tested?
- BAX69 Single-Route Arm and BAX69 Double-Route Arm
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 6 sitesUnited States
- Study dates
- 2 Nov 2015to 26 May 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of a signed informed consent
- Female participants of non-childbearing potential, ≥18 years of age
- Anticipated life expectancy >3 months at the time of screening
- Metastatic ovarian epithelial cancer that are platinum-resistant, and has no better option available in the investigator's opinion
- Recurrent symptomatic malignant ascites having required at least 2 paracenteses within a 45-day interval prior to baseline paracentesis
- Participants who have an indwelling draining IP catheter (to be drained only under medical supervision)
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- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2
- 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
- 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
- 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
- Adequate venous access
- Participant is willing and able to comply with the requirements of the protocol
Who cannot join
- Known central nervous system metastasis that is unstable within the last 2 months
- 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
- Residual AEs >Grade 2 from previous treatment
- 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)
- Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg confirmed upon repeated measures
- Left ventricular ejection fraction <50% as determined by echocardiogram (ECHO) performed at screening or within 30 days prior to C1D1
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- QT/QTc interval >480 msec, before C1D1 treatment administration, as determined by screening electrocardiogram (ECG)
- 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
- Major surgery within 4 weeks (less than 28 days) prior to C1D1
- Active joint inflammation or other immune disorder involving joints (osteoarthritis is not exclusionary)
- Active infection involving IV antibiotics within 2 weeks prior to C1D1
- Positive serology test for hepatitis B virus (HBV), hepatitis C virus (HCV), or active tuberculosis
- Positive serology test for human immunodeficiency virus (HIV) type 1 and 2, or known history of other immunodeficiency disease
- Participant has received a live vaccine within 2 weeks (less than 14 days) prior to C1D1
- Known hypersensitivity to any component of recombinant protein production by Chinese Hamster Ovary (CHO) cells
- 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
- Participant is a family member or employee of the investigator
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Georgia Regents University
Augusta, Georgia, 30912
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of Miami Miller School of Medicine
Miami, Florida, 33136
Stephenson Cancer Center at The University of Oklahoma
Oklahoma City, Oklahoma, 73104
Women's Health Specialists
Silver Spring, Maryland, 20910
Montefiore Medical Center
The Bronx, New York, 10461
About this study
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
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.
- Being tested
- BAX69 Single-Route Arm, BAX69 Double-Route Arm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BAX69 Single-Route ArmBiological
Also called Macrophage Migration Inhibitory Factor Antibody (Anti-MIF), Imalumab
Intraperitoneal (IP) only
BAX69 Double-Route ArmBiological
Also called Imalumab, Macrophage Migration Inhibitory Factor Antibody (Anti-MIF)
Intravenous (IV) infusion + intraperitoneal (IP) infusion
| Study group | Role | What they receive |
|---|---|---|
| Single-Route Arm | Experimental | BAX69 administered weekly by intraperitoneal (IP) infusion only Receives: Biological: BAX69 Single-Route Arm |
| Double-Route Arm | Experimental | BAX69 administered weekly by intravenous (IV) infusion + intraperitoneal (IP) infusion Receives: Biological: BAX69 Double-Route Arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Occurrence of Dose-limiting Toxicity (DLT)
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
Measured: 4 weeks
The Ratio of Puncture Free Survival (PuFS) Over Puncture-free Interval at Baseline
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.
Measured: 4 weeks
Secondary outcomes (12)
Ratio of Time to First Paracentesis Post-treatment Over Puncture-free Interval at Baseline
Time to first paracentesis post-treatment is calculated as the time between the last dose of Imalumab to subsequent first therapeutic paracentesis.
Measured: 4 weeks
Change in Ascites Volume Per Unit Time With Treatment
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.
Measured: Up to 4 weeks
Changes in Ascites-related Symptoms
Ascites related symptoms: anorexia, nausea, early satiety, vomiting, abdominal pain, abdominal swelling, dyspnea, fatigue, swollen ankles, heartburn
Measured: 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
Measured: Throughout the study period of approximately 22 months
Occurrence of Binding and/or Neutralizing Anti-imalumab (BAX69) Antibodies Following Treatment With Imalumab (BAX69)
Measured: Throughout the study period of approximately 22 months
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)
Measured: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Minimum Observed Concentration (Cmin)
Measured: 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)
Measured: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Half-life (t1/2)
Measured: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Apparent Systemic Clearance (CL)
Measured: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Volume of Distribution (V)
Measured: 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
QoL will be assessed using EORTC QLQ-C30.
Measured: Weekly from the baseline visit to the last week of safety follow-up (8 weeks or longer, if additional treatment will be implemented)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2015 (estimated)
- Study start2 Nov 2015
- Primary completion26 May 2016
- Study completion26 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Refractory Ovarian Cancer With Recurrent Symptomatic Malignant AscitesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Shire
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02540356
- Sponsor's protocol ID
- 391402
- Other IDs
- 2015-003492-29, 2015
- Status last verified
- Dec 2020
- First submitted
- 24 Aug 2015
- Last updated
- 12 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: 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).
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02540356
- Acronym / sponsor ID
- 391402
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 2 Nov 2015 (actual)
- Primary completion
- 26 May 2016 (actual)
- Study completion
- 26 May 2016 (actual)
- First posted
- 3 Sep 2015 (estimated)
- Results
- Posted 15 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single-Route Arm | Experimental | Biological: BAX69 Single-Route ArmBAX69 administered weekly by intraperitoneal (IP) infusion only |
| Double-Route Arm | Experimental | Biological: BAX69 Double-Route ArmBAX69 administered weekly by intravenous (IV) infusion + intraperitoneal (IP) infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Provision of a signed informed consent
- Female participants of non-childbearing potential, ≥18 years of age
- Anticipated life expectancy >3 months at the time of screening
- Metastatic ovarian epithelial cancer that are platinum-resistant, and has no better option available in the investigator's opinion
- Recurrent symptomatic malignant ascites having required at least 2 paracenteses within a 45-day interval prior to baseline paracentesis
Key exclusion criteria (17 listed)
- Known central nervous system metastasis that is unstable within the last 2 months
- 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
- Residual AEs >Grade 2 from previous treatment
- 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)
- Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg confirmed upon repeated measures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BAX69 Single-Route ArmAlso: Macrophage Migration Inhibitory Factor Antibody (Anti-MIF), ImalumabIntraperitoneal (IP) only | Biological | Single-Route Arm |
| BAX69 Double-Route ArmAlso: Imalumab, Macrophage Migration Inhibitory Factor Antibody (Anti-MIF)Intravenous (IV) infusion + intraperitoneal (IP) infusion | Biological | Double-Route Arm |
Primary outcome
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
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.
12 secondary outcomes
Ratio of Time to First Paracentesis Post-treatment Over Puncture-free Interval at Baseline
Time frame: 4 weeks
Change in Ascites Volume Per Unit Time With Treatment
Time frame: 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)
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
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
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
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
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
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
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
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
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. 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).
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Shire
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BAX69 Single-Route Arm and BAX69 Double-Route Arm in people with Refractory Ovarian Cancer With Recurrent Symptomatic Malignant Ascites, run by Baxalta now part of Shire at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Occurrence of Dose-limiting Toxicity (DLT) (time frame: 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2021.