Gemcitabine Plus Albumin-bound Paclitaxel In Patients With Advanced Metastatic Pancreatic Cancer
Study Details
Study Description
Brief Summary
To determine the maximum tolerated dose and dose-limiting toxicity of Gemcitabine plus Albumin-bound paclitaxel (ABI-007) in patients with advanced metastatic pancreatic cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Albumin-bound paclitaxel is a novel, solvent-free, albumin-bound, 130 nanometer particle form of paclitaxel designed to avoid the problems associated with solvents used in Taxol(Abraxane prescribing information 2005). Albumin has a number of properties that make it an attractive molecule to combine with paclitaxel. Albumin is a natural transporter of endogenous hydrophobic molecules such as water-insoluble vitamins and hormones (Vorum 1999)and albumin binding to the gp-60 receptor (albondin) initiates the caveolae-mediated endothelial transport of protein-bound and unbound plasma constituents (John et al 2003, Minshall et al 2003, Tiruppathi et al 1997).
This study consisted of a Phase 1 dose escalation phase, a Phase 2 treatment phase and a 24-month follow-up phase.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 100 mg/m^2 Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. |
Drug: Gemcitabine
Administered by intravenous infusion over 30 minutes.
Other Names:
Drug: Albumin-bound paclitaxel
Administered by intravenous infusion over 30 minutes.
Other Names:
|
| Experimental: 125 mg/m^2 Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. |
Drug: Gemcitabine
Administered by intravenous infusion over 30 minutes.
Other Names:
Drug: Albumin-bound paclitaxel
Administered by intravenous infusion over 30 minutes.
Other Names:
|
| Experimental: 150 mg/m^2 Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
Drug: Gemcitabine
Administered by intravenous infusion over 30 minutes.
Other Names:
Drug: Albumin-bound paclitaxel
Administered by intravenous infusion over 30 minutes.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose-limiting Toxicities [Cycle 1 (Days 1-28)]
A dose-limiting toxicity (DLT) is defined as one or more of the following toxicities related to study drug during Cycle 1, according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 3: Grade 4 neutropenia lasting >3 days in the absence of growth factor support; Grade 4 neutropenia associated with fever >38.5°C; Any other Grade 4 hematological toxicity; Grade 3 thrombocytopenia with hemorrhage; Grade 3 or 4 nausea, vomiting or diarrhea despite prophylaxis or treatment with an optimal anti-emetic or anti-diarrhea regimen; Any other Grade 3 or higher non-hematological toxicity attributable to the study drug, excluding alopecia and fatigue.
Secondary Outcome Measures
- Number of Participants With Adverse Events (AE) [Up to 25 months]
An AE was any untoward medical occurrence, not necessarily having a causal relationship with the patient's treatment, that began or worsened in grade after the start of study drug through 30 days after the last dose. A serious AE (SAE) is any untoward medical occurrence that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. Treatment-related AEs (TRAEs) include those assessed by the Investigator as possibly, probably, or definitely related to study treatment. Severity was graded according to the NCI CTCAE based on the following: Grade 1- Mild; Grade 2 -Moderate; Grade 3 - Severe; Grade 4 - Life-threatening or disabling; Grade 5 - Death related to AE.
- Percentage of Participants Who Achieved an Objective Confirmed Overall Response [Up to approximately 4 years]
Overall Response is defined as the percent of participants who achieve an objective confirmed complete (CR) or partial response (PR). Response was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, assessed by an Independent Radiological Reviewer. CR: The disappearance of all known disease and no new sites or disease-related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. PR: At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation and no new non-target lesions and/or unequivocal progression of existing non-target lesions. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing.
- Percentage of Participants With Disease Control [Up to approximately 4 years]
Disease control is defined as participants with Stable Disease for at least 16 weeks, or confirmed complete or partial overall response, based on RECIST guidelines and assessed by an Independent Radiological Reviewer. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for Progressive Disease, and no new non-target lesions or unequivocal progression of existing non-target lesions. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
- Progression-free Survival [Up to approximately 4 years]
Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first, assessed by an Independent Radiological Reviewer. Participants who do not have disease progression or have not died were censored at the last known time that the participant was progression free. Progression-free survival was summarized using Kaplan-Meier methods. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
- Duration of Response [Up to approximately 4 years]
Duration of response was assessed by progression-free survival for participants who achieved a confirmed Complete Response or Partial Response, assessed by an Independent Radiological Reviewer.
- Overall Survival [Up to approximately 4 years]
Overall survival was defined as the time from the date of first dose of study drug to the date of patient death from all causes. Participants who did not die were censored at the last known time the patient was alive. Patient survival was summarized using Kaplan-Meier methods.
- Maximal Degree of Myelosuppression [During the treatment phase, up to a maximum of 24 months.]
The maximal degree of myelosuppression was assessed by the overall nadir of absolute neutrophil count (ANC), white blood cell count and platelet count based on clinical laboratory measurements.
- Maximal Degree of Anemia [During the treatment phase, up to a maximum of 24 months.]
The maximal degree of anemia (and myelosuppression) was assessed by the overall (any time after first dose of study drug) nadir of hemoglobin levels based on clinical laboratory measurements.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patient has histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cell neoplasms are excluded.
-
Male or non-pregnant and non-lactating female, and age greater or equal to 18.
-
If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test beta-human chorionic gonadotropin (B-hCG) documented within 72 hours of the first administration of study drug.
-
If sexually active, the patient must agree to use contraception considered adequate and appropriate by the investigator.
-
Patient must have received no prior therapy for the treatment of metastatic disease. Prior treatment with 5-fluorouracil (5-FU) or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. If a patient received gemcitabine in the adjuvant setting, tumor recurrence must have occurred at least 6 months after completing the last dose of gemcitabine.
-
Patient has the following blood counts at baseline
-
Absolute neutrophil count (ANC) equal or greater to 1.5 x 10^9/L;
-
Platelets equal or greater to 100 x 10^9/L
-
Hemoglobin equal or greater to 9 g/dL.
-
Patient has the following blood chemistry levels at baseline:
-
Aspartate aminotransferase (SGOT), Alanine aminotransferase (SGPT) equal or less than 2.5 x upper limit of normal range (ULN) is allowed
-
Bilirubin less than or equal to ULN
-
Serum creatinine within normal limits or calculated clearance equal or greater to 60 mL/min/1.73M^2 patients with serum creatinine levels above the institutional normal value
-
Patient has no clinically significant abnormalities in urinalysis results
-
Patient has acceptable coagulation status as indicated by a prothrombin time (PT) within normal limits (plus or minus 15%) and partial thromboplastin time (PTT) within normal limits (plus or minus 15%).
-
Patient has a Karnofsky performance status (KPS) greater or equal to 70 (Eastern Cooperative Oncology Group [ECOG] PS 0-1).
-
Patient has one or more metastatic tumors measurable by computed tomography (CT) scan.
-
Patient has been informed about the nature of study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities.
Exclusion Criteria:
-
Patient has known brain metastases unless previously treated and well controlled for at least 3 months (defined as stable clinically, no edema, no steroids and stable in two scans at least 4 weeks apart).
-
Patient uses therapeutic coumadin for a history of pulmonary emboli and deep vein thrombosis (DVT).
-
Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
-
Patient has known infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C.
-
Patient has undergone major surgery, other than diagnostic surgery i.e.-- done to obtain a biopsy for diagnosis without removal of an organ), with 4 weeks prior to Day 1 of treatment in this study.
-
Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy within 3 weeks prior to study entry weeks (6 weeks for nitrosureas or mitomycin C).
-
Patient has a history of allergy or hypersensitivity to the study drug.
-
Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug.
-
Patient is unwilling or unable to comply with study procedures.
-
Patient is enrolled in any other clinical protocol or investigational trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham Comprehensive Cancer Ctr | Birmingham | Alabama | United States | |
| 2 | Scottsdale Healthcare/Virginia Pipe Cancer Institute | Scottsdale | Arizona | United States | 85258 |
| 3 | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University | Baltimore | Maryland | United States | 35233 |
| 4 | Virigina Piper Cancer Institute | Minneapolis | Minnesota | United States | 55407 |
| 5 | South Texas Oncology & Hematology | San Antonio | Texas | United States | 78258 |
Sponsors and Collaborators
- Celgene
Investigators
- Principal Investigator: Daniel Von Hoff, MD, Scottsdale Clinical Research Institute
Study Documents (Full-Text)
None provided.More Information
Publications
- CA040
Study Results
Participant Flow
| Recruitment Details | Enrollment was initiated in November 2006 and completed in September 2008. Sixty-seven patients were enrolled at four sites in the US. |
|---|---|
| Pre-assignment Detail | In Phase 1, patients were assigned sequentially to one of the three potential dose levels based on the dose cohort currently enrolling patients (a total of 30 patients). After the maximum tolerated dose (MTD) was determined, all subsequent patients were enrolled at that dose level in Phase 2 (37 patients). |
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
| Period Title: Overall Study | |||
| STARTED | 20 | 44 | 3 |
| Phase 1, Dose Escalation Population | 20 | 7 | 3 |
| COMPLETED | 11 | 21 | 1 |
| NOT COMPLETED | 9 | 23 | 2 |
Baseline Characteristics
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. | Total of all reporting groups |
| Overall Participants | 20 | 44 | 3 | 67 |
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
62.0
|
61.5
|
69.0
|
62.0
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
9
45%
|
25
56.8%
|
1
33.3%
|
35
52.2%
|
| Male |
11
55%
|
19
43.2%
|
2
66.7%
|
32
47.8%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||
| Asian |
1
5%
|
1
2.3%
|
0
0%
|
2
3%
|
| Black, of African Heritage |
0
0%
|
2
4.5%
|
0
0%
|
2
3%
|
| White, Non-Hispanic, and Non-Latino |
16
80%
|
37
84.1%
|
1
33.3%
|
54
80.6%
|
| White, Hispanic, or Latino |
2
10%
|
4
9.1%
|
2
66.7%
|
8
11.9%
|
| Other |
1
5%
|
0
0%
|
0
0%
|
1
1.5%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
20
100%
|
44
100%
|
3
100%
|
67
100%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number] | ||||
| 0 (Fully Active) |
9
45%
|
22
50%
|
2
66.7%
|
33
49.3%
|
| 1 (Restrictive but Ambulatory) |
11
55%
|
22
50%
|
1
33.3%
|
34
50.7%
|
| Histology of Primary Diagnosis: Adenocarcinoma (participants) [Number] | ||||
| Number [participants] |
20
100%
|
44
100%
|
3
100%
|
67
100%
|
| Time from First Documented Metastasis/Relapse to Study Entry (months) [Median (Full Range) ] | ||||
| Median (Full Range) [months] |
0.8
|
0.7
|
0.3
|
0.7
|
| Current Site(s) of Metastasis/Relapse (participants) [Number] | ||||
| Skin/Soft Tissue |
0
0%
|
1
2.3%
|
0
0%
|
1
1.5%
|
| Supraclavicular Nodes |
0
0%
|
2
4.5%
|
0
0%
|
2
3%
|
| Axilla |
2
10%
|
0
0%
|
0
0%
|
2
3%
|
| Bone |
1
5%
|
3
6.8%
|
0
0%
|
4
6%
|
| Lung/Thoracic |
5
25%
|
18
40.9%
|
1
33.3%
|
24
35.8%
|
| Liver |
11
55%
|
33
75%
|
2
66.7%
|
46
68.7%
|
| Abdomen/Peritoneum |
16
80%
|
37
84.1%
|
1
33.3%
|
54
80.6%
|
| Pelvis |
1
5%
|
3
6.8%
|
1
33.3%
|
5
7.5%
|
| Other |
8
40%
|
6
13.6%
|
0
0%
|
14
20.9%
|
| Dominant Current Site of Metastasis/Relapse (participants) [Number] | ||||
| Visceral |
19
95%
|
44
100%
|
3
100%
|
66
98.5%
|
| Non-visceral |
1
5%
|
0
0%
|
0
0%
|
1
1.5%
|
Outcome Measures
| Title | Number of Participants With Dose-limiting Toxicities |
|---|---|
| Description | A dose-limiting toxicity (DLT) is defined as one or more of the following toxicities related to study drug during Cycle 1, according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 3: Grade 4 neutropenia lasting >3 days in the absence of growth factor support; Grade 4 neutropenia associated with fever >38.5°C; Any other Grade 4 hematological toxicity; Grade 3 thrombocytopenia with hemorrhage; Grade 3 or 4 nausea, vomiting or diarrhea despite prophylaxis or treatment with an optimal anti-emetic or anti-diarrhea regimen; Any other Grade 3 or higher non-hematological toxicity attributable to the study drug, excluding alopecia and fatigue. |
| Time Frame | Cycle 1 (Days 1-28) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 1 treated population |
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 20 | 7 | 3 |
| Number [participants] |
4
20%
|
0
0%
|
1
33.3%
|
| Title | Number of Participants With Adverse Events (AE) |
|---|---|
| Description | An AE was any untoward medical occurrence, not necessarily having a causal relationship with the patient's treatment, that began or worsened in grade after the start of study drug through 30 days after the last dose. A serious AE (SAE) is any untoward medical occurrence that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. Treatment-related AEs (TRAEs) include those assessed by the Investigator as possibly, probably, or definitely related to study treatment. Severity was graded according to the NCI CTCAE based on the following: Grade 1- Mild; Grade 2 -Moderate; Grade 3 - Severe; Grade 4 - Life-threatening or disabling; Grade 5 - Death related to AE. |
| Time Frame | Up to 25 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated patients: all enrolled patients who received at least one dose of study drug. |
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 20 | 44 | 3 |
| Patients with at least 1 AE |
20
100%
|
44
100%
|
3
100%
|
| At least 1 grade 3 or higher AE |
15
75%
|
42
95.5%
|
3
100%
|
| At least 1 treatment-related AE |
18
90%
|
42
95.5%
|
3
100%
|
| At least 1 treatment-related grade 3 to 5 AE |
11
55%
|
38
86.4%
|
3
100%
|
| Patients with at least 1 SAE |
10
50%
|
24
54.5%
|
1
33.3%
|
| Patients with at least 1 treatment-related SAE |
4
20%
|
12
27.3%
|
1
33.3%
|
| At least 1 AE and drug permanently discontinued |
3
15%
|
12
27.3%
|
2
66.7%
|
| At least 1 TRAE and drug permanently discontinued |
2
10%
|
8
18.2%
|
2
66.7%
|
| At least 1 dose reduction due to TRAE |
4
20%
|
10
22.7%
|
1
33.3%
|
| At least 1 dose interruption due to AE |
1
5%
|
0
0%
|
0
0%
|
| At least 1 treatment-related AE dose interruption |
1
5%
|
0
0%
|
0
0%
|
| At least 1 treatment-emergent dose delay due to AE |
14
70%
|
27
61.4%
|
3
100%
|
| At least 1 treatment-related dose delay due to AE |
13
65%
|
27
61.4%
|
3
100%
|
| At least 1 AE resulting in death |
0
0%
|
1
2.3%
|
1
33.3%
|
| Title | Percentage of Participants Who Achieved an Objective Confirmed Overall Response |
|---|---|
| Description | Overall Response is defined as the percent of participants who achieve an objective confirmed complete (CR) or partial response (PR). Response was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, assessed by an Independent Radiological Reviewer. CR: The disappearance of all known disease and no new sites or disease-related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. PR: At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation and no new non-target lesions and/or unequivocal progression of existing non-target lesions. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. |
| Time Frame | Up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated patients |
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 20 | 44 | 3 |
| Number (95% Confidence Interval) [percentage of participants] |
25
125%
|
39
88.6%
|
0
0%
|
| Title | Percentage of Participants With Disease Control |
|---|---|
| Description | Disease control is defined as participants with Stable Disease for at least 16 weeks, or confirmed complete or partial overall response, based on RECIST guidelines and assessed by an Independent Radiological Reviewer. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for Progressive Disease, and no new non-target lesions or unequivocal progression of existing non-target lesions. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. |
| Time Frame | Up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated patients |
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 20 | 44 | 3 |
| Number (95% Confidence Interval) [percentage of participants] |
55
275%
|
55
125%
|
33
1100%
|
| Title | Progression-free Survival |
|---|---|
| Description | Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first, assessed by an Independent Radiological Reviewer. Participants who do not have disease progression or have not died were censored at the last known time that the participant was progression free. Progression-free survival was summarized using Kaplan-Meier methods. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. |
| Time Frame | Up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated patients |
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 20 | 44 | 3 |
| Median (95% Confidence Interval) [months] |
6.1
|
6.9
|
1.6
|
| Title | Duration of Response |
|---|---|
| Description | Duration of response was assessed by progression-free survival for participants who achieved a confirmed Complete Response or Partial Response, assessed by an Independent Radiological Reviewer. |
| Time Frame | Up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated patients with an overall confirmed Complete Response or Partial Response. |
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 5 | 17 | 0 |
| Median (95% Confidence Interval) [months] |
NA
|
7.3
|
| Title | Overall Survival |
|---|---|
| Description | Overall survival was defined as the time from the date of first dose of study drug to the date of patient death from all causes. Participants who did not die were censored at the last known time the patient was alive. Patient survival was summarized using Kaplan-Meier methods. |
| Time Frame | Up to approximately 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated patients |
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 20 | 44 | 3 |
| Median (95% Confidence Interval) [months] |
9.3
|
12.2
|
6.1
|
| Title | Maximal Degree of Myelosuppression |
|---|---|
| Description | The maximal degree of myelosuppression was assessed by the overall nadir of absolute neutrophil count (ANC), white blood cell count and platelet count based on clinical laboratory measurements. |
| Time Frame | During the treatment phase, up to a maximum of 24 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated patients with available data |
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 20 | 43 | 3 |
| Absolute neutrophil count |
1.38
(1.541)
|
0.96
(1.446)
|
0.47
(0.460)
|
| White blood cell count |
2.69
(1.734)
|
2.18
(1.849)
|
1.52
(1.484)
|
| Platelet count |
120.3
(79.02)
|
88.3
(62.10)
|
58.7
(48.64)
|
| Title | Maximal Degree of Anemia |
|---|---|
| Description | The maximal degree of anemia (and myelosuppression) was assessed by the overall (any time after first dose of study drug) nadir of hemoglobin levels based on clinical laboratory measurements. |
| Time Frame | During the treatment phase, up to a maximum of 24 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated patients with available data |
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 20 | 43 | 3 |
| Mean (Standard Deviation) [g/L] |
95.1
(12.85)
|
91.8
(10.43)
|
95.3
(15.37)
|
Adverse Events
| Time Frame | Adverse events were collected up to 30 days after the last dose (a maximum of 25 months). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 | |||
| Arm/Group Description | Participants received albumin-bound paclitaxel 100 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level one). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level two). Treatment continued until progressive disease or unacceptable toxicity. | Participants received albumin-bound paclitaxel 150 mg/m^2 followed by gemcitabine 1000 mg/m^2 by intravenous infusion (IV) on Days 1, 8 and 15 of each 28 day cycle (dose level three). Treatment continued until progressive disease or unacceptable toxicity. | |||
All Cause Mortality |
||||||
| 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/20 (50%) | 24/44 (54.5%) | 1/3 (33.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Pancytopenia | 0/20 (0%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Anaemia | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Neutropenia | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Thrombocytopenia | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Supraventricular tachycardia | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Gastrointestinal haemorrhage | 0/20 (0%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Intestinal obstruction | 0/20 (0%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Small intestinal obstruction | 0/20 (0%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Ascites | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Duodenal obstruction | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Enterocutaneous fistula | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Ileus | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Ileus paralytic | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Nausea | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Obstruction gastric | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| General disorders | ||||||
| Pyrexia | 1/20 (5%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Pain | 2/20 (10%) | 0/44 (0%) | 0/3 (0%) | |||
| Hernia obstructive | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Hepatobiliary disorders | ||||||
| Bile duct obstruction | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Cholangitis | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Infections and infestations | ||||||
| Pneumonia | 1/20 (5%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Bacteraemia | 0/20 (0%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Neutropenic sepsis | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Abdominal wall abscess | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Cellulitis | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Clostridium difficile colitis | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Endocarditis | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Infection | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Sepsis | 0/20 (0%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Urinary tract infection | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Hip fracture | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Medical device complication | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Dehydration | 2/20 (10%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Muscular weakness | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Nervous system disorders | ||||||
| Loss of consciousness | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Cerebrovascular accident | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Convulsion | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Migraine with aura | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Sedation | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Syncope | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Psychiatric disorders | ||||||
| Mental status changes | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Renal and urinary disorders | ||||||
| Hydronephrosis | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Ureteric obstruction | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Respiratory failure | 0/20 (0%) | 1/44 (2.3%) | 0/3 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| 100 mg/m^2 | 125 mg/m^2 | 150 mg/m^2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/20 (100%) | 44/44 (100%) | 3/3 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 12/20 (60%) | 30/44 (68.2%) | 2/3 (66.7%) | |||
| Bone marrow failure | 0/20 (0%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Leukopenia | 4/20 (20%) | 18/44 (40.9%) | 2/3 (66.7%) | |||
| Lymphadenitis | 0/20 (0%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Lymphadenopathy | 0/20 (0%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Neutropenia | 10/20 (50%) | 25/44 (56.8%) | 2/3 (66.7%) | |||
| Thrombocytopenia | 5/20 (25%) | 26/44 (59.1%) | 2/3 (66.7%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 1/20 (5%) | 1/44 (2.3%) | 1/3 (33.3%) | |||
| Bradycardia | 0/20 (0%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Palpitations | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Tachycardia | 2/20 (10%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Ventricular extrasystoles | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Ear pain | 2/20 (10%) | 0/44 (0%) | 0/3 (0%) | |||
| Hypoacusis | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Endocrine disorders | ||||||
| Steroid withdrawal syndrome | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Eye disorders | ||||||
| Blepharitis | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Conjunctival haemorrhage | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Conjunctivitis | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Diplopia | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Dry eye | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Eye swelling | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Vision blurred | 2/20 (10%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Visual impairment | 1/20 (5%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal distension | 4/20 (20%) | 9/44 (20.5%) | 1/3 (33.3%) | |||
| Abdominal pain | 7/20 (35%) | 17/44 (38.6%) | 2/3 (66.7%) | |||
| Abdominal pain lower | 3/20 (15%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Abdominal pain upper | 2/20 (10%) | 4/44 (9.1%) | 0/3 (0%) | |||
| Colitis | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Constipation | 6/20 (30%) | 21/44 (47.7%) | 0/3 (0%) | |||
| Diarrhoea | 7/20 (35%) | 23/44 (52.3%) | 2/3 (66.7%) | |||
| Dry mouth | 3/20 (15%) | 0/44 (0%) | 0/3 (0%) | |||
| Dyspepsia | 0/20 (0%) | 5/44 (11.4%) | 0/3 (0%) | |||
| Dysphagia | 2/20 (10%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Eructation | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Faecal incontinence | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Flatulence | 1/20 (5%) | 2/44 (4.5%) | 1/3 (33.3%) | |||
| Gastrooesophageal reflux disease | 1/20 (5%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Haemorrhoids | 0/20 (0%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Hiatus hernia | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Impaired gastric emptying | 0/20 (0%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Melaena | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Mouth ulceration | 1/20 (5%) | 2/44 (4.5%) | 1/3 (33.3%) | |||
| Nausea | 8/20 (40%) | 29/44 (65.9%) | 2/3 (66.7%) | |||
| Odynophagia | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Oral mucosal erythema | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Oral pain | 2/20 (10%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Retching | 1/20 (5%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Stomatitis | 2/20 (10%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Vomiting | 5/20 (25%) | 20/44 (45.5%) | 2/3 (66.7%) | |||
| General disorders | ||||||
| Asthenia | 1/20 (5%) | 7/44 (15.9%) | 1/3 (33.3%) | |||
| Catheter related complication | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Catheter site inflammation | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Chest discomfort | 2/20 (10%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Chest pain | 2/20 (10%) | 3/44 (6.8%) | 1/3 (33.3%) | |||
| Chills | 5/20 (25%) | 10/44 (22.7%) | 1/3 (33.3%) | |||
| Fatigue | 15/20 (75%) | 39/44 (88.6%) | 3/3 (100%) | |||
| Influenza like illness | 1/20 (5%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Infusion site pain | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Injection site extravasation | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Local swelling | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Malaise | 0/20 (0%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Mucosal dryness | 0/20 (0%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Mucosal inflammation | 1/20 (5%) | 11/44 (25%) | 1/3 (33.3%) | |||
| Oedema peripheral | 7/20 (35%) | 27/44 (61.4%) | 1/3 (33.3%) | |||
| Pain | 3/20 (15%) | 4/44 (9.1%) | 0/3 (0%) | |||
| Pyrexia | 8/20 (40%) | 20/44 (45.5%) | 1/3 (33.3%) | |||
| Hepatobiliary disorders | ||||||
| Bile duct obstruction | 0/20 (0%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Hyperbilirubinaemia | 1/20 (5%) | 1/44 (2.3%) | 1/3 (33.3%) | |||
| Portal vein thrombosis | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Immune system disorders | ||||||
| Seasonal allergy | 2/20 (10%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Infections and infestations | ||||||
| Candidiasis | 2/20 (10%) | 5/44 (11.4%) | 0/3 (0%) | |||
| Cellulitis | 3/20 (15%) | 5/44 (11.4%) | 0/3 (0%) | |||
| Folliculitis | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Fungal infection | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Infection | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Lobar pneumonia | 0/20 (0%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Localised infection | 0/20 (0%) | 1/44 (2.3%) | 1/3 (33.3%) | |||
| Oral candidiasis | 1/20 (5%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Pneumonia | 1/20 (5%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Rash pustular | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Sinusitis | 3/20 (15%) | 4/44 (9.1%) | 0/3 (0%) | |||
| Upper respiratory tract infection | 0/20 (0%) | 4/44 (9.1%) | 0/3 (0%) | |||
| Urinary tract infection | 1/20 (5%) | 7/44 (15.9%) | 0/3 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 1/20 (5%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Incision site complication | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Medical device pain | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Nail avulsion | 0/20 (0%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Post-traumatic pain | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Procedural pain | 0/20 (0%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Procedural site reaction | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Stent occlusion | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Sunburn | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 6/20 (30%) | 4/44 (9.1%) | 0/3 (0%) | |||
| Aspartate aminotransferase increased | 5/20 (25%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Blood albumin decreased | 1/20 (5%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Blood alkaline phosphatase increased | 4/20 (20%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Blood creatinine increased | 2/20 (10%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Blood urine present | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Neutrophil count decreased | 0/20 (0%) | 9/44 (20.5%) | 0/3 (0%) | |||
| Platelet count decreased | 1/20 (5%) | 1/44 (2.3%) | 1/3 (33.3%) | |||
| Weight decreased | 2/20 (10%) | 8/44 (18.2%) | 1/3 (33.3%) | |||
| Weight increased | 1/20 (5%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 9/20 (45%) | 22/44 (50%) | 2/3 (66.7%) | |||
| Dehydration | 6/20 (30%) | 12/44 (27.3%) | 2/3 (66.7%) | |||
| Hyperglycaemia | 0/20 (0%) | 4/44 (9.1%) | 1/3 (33.3%) | |||
| Hypoalbuminaemia | 2/20 (10%) | 4/44 (9.1%) | 1/3 (33.3%) | |||
| Hypocalcaemia | 1/20 (5%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Hypoglycaemia | 0/20 (0%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Hypokalaemia | 2/20 (10%) | 12/44 (27.3%) | 1/3 (33.3%) | |||
| Hypomagnesaemia | 1/20 (5%) | 4/44 (9.1%) | 1/3 (33.3%) | |||
| Hyponatraemia | 2/20 (10%) | 4/44 (9.1%) | 1/3 (33.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/20 (10%) | 10/44 (22.7%) | 0/3 (0%) | |||
| Back pain | 2/20 (10%) | 5/44 (11.4%) | 0/3 (0%) | |||
| Bone pain | 2/20 (10%) | 2/44 (4.5%) | 1/3 (33.3%) | |||
| Bunion | 0/20 (0%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Flank pain | 1/20 (5%) | 1/44 (2.3%) | 1/3 (33.3%) | |||
| Joint contracture | 0/20 (0%) | 0/44 (0%) | 1/3 (33.3%) | |||
| Muscle spasms | 0/20 (0%) | 1/44 (2.3%) | 1/3 (33.3%) | |||
| Muscular weakness | 2/20 (10%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Musculoskeletal chest pain | 1/20 (5%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Musculoskeletal pain | 2/20 (10%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Musculoskeletal stiffness | 0/20 (0%) | 4/44 (9.1%) | 0/3 (0%) | |||
| Myalgia | 0/20 (0%) | 10/44 (22.7%) | 1/3 (33.3%) | |||
| Neck pain | 1/20 (5%) | 3/44 (6.8%) | 1/3 (33.3%) | |||
| Pain in extremity | 4/20 (20%) | 9/44 (20.5%) | 0/3 (0%) | |||
| Nervous system disorders | ||||||
| Balance disorder | 2/20 (10%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Burning sensation | 2/20 (10%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Cognitive disorder | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Dizziness | 8/20 (40%) | 13/44 (29.5%) | 2/3 (66.7%) | |||
| Dysarthria | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Dysgeusia | 3/20 (15%) | 16/44 (36.4%) | 2/3 (66.7%) | |||
| Head discomfort | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Headache | 7/20 (35%) | 9/44 (20.5%) | 1/3 (33.3%) | |||
| Hypoaesthesia | 1/20 (5%) | 4/44 (9.1%) | 0/3 (0%) | |||
| Migraine | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Neuropathy peripheral | 5/20 (25%) | 29/44 (65.9%) | 2/3 (66.7%) | |||
| Paraesthesia | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Peripheral motor neuropathy | 0/20 (0%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Peripheral nerve palsy | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Peripheral sensory neuropathy | 3/20 (15%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Sinus headache | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Somnolence | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Syncope | 1/20 (5%) | 2/44 (4.5%) | 1/3 (33.3%) | |||
| Psychiatric disorders | ||||||
| Agitation | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Anxiety | 2/20 (10%) | 13/44 (29.5%) | 0/3 (0%) | |||
| Confusional state | 2/20 (10%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Depressed mood | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Depression | 1/20 (5%) | 8/44 (18.2%) | 0/3 (0%) | |||
| Insomnia | 7/20 (35%) | 13/44 (29.5%) | 0/3 (0%) | |||
| Restlessness | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Renal and urinary disorders | ||||||
| Bladder spasm | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Dysuria | 1/20 (5%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Haematuria | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Incontinence | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Proteinuria | 1/20 (5%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Renal pain | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Urinary incontinence | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Urinary tract disorder | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Breast pain | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 5/20 (25%) | 13/44 (29.5%) | 0/3 (0%) | |||
| Dyspnoea | 7/20 (35%) | 11/44 (25%) | 1/3 (33.3%) | |||
| Dyspnoea exertional | 1/20 (5%) | 4/44 (9.1%) | 1/3 (33.3%) | |||
| Epistaxis | 2/20 (10%) | 10/44 (22.7%) | 0/3 (0%) | |||
| Hypoxia | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Lung infiltration | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Nasal congestion | 2/20 (10%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Oropharyngeal pain | 1/20 (5%) | 6/44 (13.6%) | 0/3 (0%) | |||
| Pleural effusion | 1/20 (5%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Rhinorrhoea | 2/20 (10%) | 6/44 (13.6%) | 0/3 (0%) | |||
| Wheezing | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 15/20 (75%) | 35/44 (79.5%) | 1/3 (33.3%) | |||
| Decubitus ulcer | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Dry skin | 2/20 (10%) | 3/44 (6.8%) | 1/3 (33.3%) | |||
| Erythema | 1/20 (5%) | 10/44 (22.7%) | 1/3 (33.3%) | |||
| Hyperhidrosis | 1/20 (5%) | 5/44 (11.4%) | 1/3 (33.3%) | |||
| Nail discolouration | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Nail disorder | 2/20 (10%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Night sweats | 4/20 (20%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Palmar-plantar erythrodysaesthesia syndrome | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Petechiae | 0/20 (0%) | 1/44 (2.3%) | 1/3 (33.3%) | |||
| Pruritus | 5/20 (25%) | 10/44 (22.7%) | 0/3 (0%) | |||
| Rash | 7/20 (35%) | 22/44 (50%) | 2/3 (66.7%) | |||
| Skin hyperpigmentation | 1/20 (5%) | 1/44 (2.3%) | 0/3 (0%) | |||
| Skin lesion | 0/20 (0%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Urticaria | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Surgical and medical procedures | ||||||
| Biliary drainage | 1/20 (5%) | 0/44 (0%) | 0/3 (0%) | |||
| Vascular disorders | ||||||
| Deep vein thrombosis | 0/20 (0%) | 5/44 (11.4%) | 0/3 (0%) | |||
| Flushing | 2/20 (10%) | 2/44 (4.5%) | 0/3 (0%) | |||
| Hypertension | 1/20 (5%) | 3/44 (6.8%) | 0/3 (0%) | |||
| Hypotension | 3/20 (15%) | 5/44 (11.4%) | 0/3 (0%) | |||
| Orthostatic hypotension | 2/20 (10%) | 6/44 (13.6%) | 1/3 (33.3%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Institution may publish the results of its findings if a multicenter publication is not forthcoming within 18 months after study completion. Institution shall provide Celgene with a copy of the papers prior to their submission; Celgene shall complete its review within 30 days after receipt. Upon Celgene's request, proposed publication or presentation can be delayed up to 60 additional days to enable Celgene to secure adequate intellectual property protection of patentable material.
Results Point of Contact
| Name/Title | Associate Director, Clinical Trials Disclosure |
|---|---|
| Organization | Celgene Corporation |
| Phone | 1-888-260-1599 |
| clinicaltrialdisclosure@celgene.com |
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