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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-003492-29 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single-Route Arm | Experimental | BAX69 administered weekly by intraperitoneal (IP) infusion only |
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| Double-Route Arm | Experimental | BAX69 administered weekly by intravenous (IV) infusion + intraperitoneal (IP) infusion |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BAX69 Single-Route Arm | Biological | Intraperitoneal (IP) only |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 4 weeks |
| Change in Ascites Volume Per Unit Time With Treatment |
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Inclusion Criteria:
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)
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2
Adequate hematological function, defined as:
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:
Adequate venous access
Participant is willing and able to comply with the requirements of the protocol
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Shire | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami Miller School of Medicine | Miami | Florida | 33136 | United States | ||
| Georgia Regents University |
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).
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2 participants were enrolled for this study and 1 participant was a screen failure. Study was stopped early with only 1 participant having been dosed.
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| ID | Title | Description |
|---|---|---|
| FG000 | Single-Route Arm | BAX69 administered weekly by intraperitoneal (IP) infusion as 1 of the following predefined dose regimens: 5mg/kg (Cohort S1), 10mg/kg (Cohort S2), 15mg/kg (Cohort S3) |
| FG001 | Double-Route Arm |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| BAX69 Double-Route Arm | Biological | Intravenous (IV) infusion + intraperitoneal (IP) infusion |
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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 | 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 | Throughout the study period of approximately 22 months |
| Occurrence of Binding and/or Neutralizing Anti-imalumab (BAX69) Antibodies Following Treatment With Imalumab (BAX69) | Throughout the study period of approximately 22 months |
| Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) | Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours |
| Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Minimum Observed Concentration (Cmin) | 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) | Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours |
| Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Half-life (t1/2) | Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours |
| Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Apparent Systemic Clearance (CL) | Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours |
| Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Volume of Distribution (V) | 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. | Weekly from the baseline visit to the last week of safety follow-up (8 weeks or longer, if additional treatment will be implemented) |
| Augusta |
| Georgia |
| 30912 |
| United States |
| Women's Health Specialists | Silver Spring | Maryland | 20910 | United States |
| Montefiore Medical Center | The Bronx | New York | 10461 | United States |
| Stephenson Cancer Center at The University of Oklahoma | Oklahoma City | Oklahoma | 73104 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
BAX69 administered weekly by intravenous (IV) infusion + intraperitoneal (IP) infusion as 1 of the following predefined dose regimens: 5mg/kg IV + 5mg/kg IP (Cohort D1), 10mg/kg IV + 5mg/kg IP (Cohort D2), 10mg/kg IV + 10mg/kg IP (Cohort D3)
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| ID | Title | Description |
|---|---|---|
| BG000 | Single-Route Arm | BAX69 administered weekly by intraperitoneal (IP) infusion as 1 of the following predefined dose regimens: 5mg/kg (Cohort S1), 10mg/kg (Cohort S2), 15mg/kg (Cohort S3) |
| BG001 | Double-Route Arm | BAX69 administered weekly by intravenous (IV) infusion + intraperitoneal (IP) infusion as 1 of the following predefined dose regimens: 5mg/kg IV + 5mg/kg IP (Cohort D1), 10mg/kg IV + 5mg/kg IP (Cohort D2), 10mg/kg IV + 10mg/kg IP (Cohort D3) |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
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| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. | Posted | Count of Participants | Participants | 4 weeks |
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| Primary | 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. | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | 4 weeks |
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| Secondary | 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. | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | 4 weeks |
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| Secondary | 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. | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | Up to 4 weeks |
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| Secondary | Changes in Ascites-related Symptoms | Ascites related symptoms: anorexia, nausea, early satiety, vomiting, abdominal pain, abdominal swelling, dyspnea, fatigue, swollen ankles, heartburn | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | Baseline, weekly during the treatment period, and every 2 weeks during the safety follow-up period, up to approximately 6 months) |
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| Secondary | Occurrence of Serious Adverse Events (SAEs) and/or Treatment-emergent Adverse Events (TEAEs), Regardless of Causality or Relationship to Study Drug | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. | Posted | Count of Participants | Participants | Throughout the study period of approximately 22 months |
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| Secondary | Occurrence of Binding and/or Neutralizing Anti-imalumab (BAX69) Antibodies Following Treatment With Imalumab (BAX69) | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | Throughout the study period of approximately 22 months |
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| Secondary | Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours |
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| Secondary | Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Minimum Observed Concentration (Cmin) | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours |
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| Secondary | Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Area Under the Concentration vs Time Curve (AUC) | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours |
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| Secondary | Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Half-life (t1/2) | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours |
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| Secondary | Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Apparent Systemic Clearance (CL) | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours |
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| Secondary | Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Volume of Distribution (V) | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours |
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| Secondary | 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. | Study was terminated early with only one participant dosed. No statistical analysis was performed on this outcome measure. Additionally, due to concerns that the participant would be at risk of being re-identified, study results are not posted. | Posted | Weekly from the baseline visit to the last week of safety follow-up (8 weeks or longer, if additional treatment will be implemented) |
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From the first dose of Imalumab (BAX69) until study completion/discontinuation or 56 (±2 days) following the last dose of Imalumab.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Overall Trial | Treatment with Imalumab (BAX69) over a 4-week treatment period administered weekly at one of the following dose regimens: BAX69 5mg/kg IP (intraperitoneal) (Cohort S1), 10mg/kg IP (Cohort S2), 15mg/kg IP (Cohort S3), 5mg/kg IV (intravenous) + 5mg/kg IP (intraperitoneal) (Cohort D1), 10mg/kg IV + 5mg/kg IP (Cohort D2), 10mg/kg IV + 10mg/kg IP (Cohort D3) | 0 | 1 | 0 | 1 | 1 | 1 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distention (Grade 2) | Gastrointestinal disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Hypokalemia (Grade 1) | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Hypomagnesemia (Grade 1) | Metabolism and nutrition disorders | MedDRA 18.0 | Non-systematic Assessment |
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| Right knee pain (Grade 1) | Musculoskeletal and connective tissue disorders | MedDRA 18.0 | Non-systematic Assessment |
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Study was terminated early with only 1 subject having been dosed. Therefore no statistical analysis was performed on the outcome measures. Only descriptive data for one subject are available.
Agreements with PIs may vary per requirements of individual PI, but contain common elements. For this study, PIs are restricted from independently publishing results until completion of the multi-center publication or twelve months following the conclusion of the study at all sites, whichever is first. Baxalta requires a review of results communication at least 90 days prior to submission. Baxalta may request an additional delay up to 60 days (e.g. for intellectual property protection).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Registries and Results Disclosure | Baxalta, now part of Shire | ClinicalTrialsDisclosure@baxalta.com |
| >=65 years |
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| Participants |
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