A Study of Trabectedin or Dacarbazine for the Treatment of Patients With Advanced Liposarcoma or Leiomyosarcoma
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate whether overall survival for the trabectedin group is superior to the dacarbazine group for patients with advanced L-sarcoma (liposarcoma or leiomyosarcoma).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This is a randomized study (study drug assigned by chance) using a 2:1 randomization. It is an open-label (all people know study drug), active-controlled (comparing to a different drug used for the same condition), parallel-group (different treatment groups continue with separate treatments throughout the study), multicenter study. This study will be divided into 3 phases, screening, treatment, follow-up and optional extension phase (OEP). During screening, potential participants will be assessed for study eligibility after providing signed informed consent. Approximately 570 patients who satisfy all inclusion and exclusion criteria will be randomly assigned in a 2:1 ratio to either the trabectedin (n=380) or dacarbazine (n=190) treatment groups. During the treatment phase, patients will receive study drug once every 3 weeks, until disease progression (defined by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1 criteria) or signs of toxicity. Assessments will be performed to evaluate the effectiveness of the drug, and patient safety will be monitored. During the follow-up phase, after the last dose of study drug, clinical outcomes for patients will be evaluated. Trabectedin will be administered at a dose of 1.5 milligram per square meters (mg/m2) through a catheter into a large vein as a 24-hour intravenous (IV) infusion, once every 3 weeks, until disease progression or signs of toxicity. Dacarbazine will be administered at a dose of 1.0 g/m2 as a 20-120 minute infusion, once every 3 weeks, until disease progression or signs of toxicity. In the OEP, participants who were previously randomized to the dacarbazine group will have the option to receive trabectedin at the discretion of the investigator.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Trabectedin
|
Drug: Trabectedin
Type=exactly number, unit=mg/m2, number=1.5, form=intravenous infusion, route=intravenous use. Once every 3 weeks until disease progression or signs of toxicity.
|
| Active Comparator: Dacarbazine
|
Drug: Dacarbazine
Type=exactly number, unit=g/m2, number=1, form=intravenous infusion, route=intravenous use. Once every 3 weeks until disease progression or signs of toxicity.
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015]]
The OS is defined as the time from the date of first dose of study drug to date of death from any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive.
Secondary Outcome Measures
- Progression-Free Survival (PFS) [approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013])]
The Progression-Free Survival (PFS) was assessed as median number of months from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier. Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed.
- Time to Progression [approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013])]
Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first. Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed.
- Objective Response Rate [approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013])]
The objective response rate (ORR) is defined as the percentage of participants who achieved a Complete response (CR) or partial response (PR) as best responses. according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST). CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response. Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed.
- Duration of Response [approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013])]
Duration of response is defined as the time from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death. Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed.
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015])]
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically proven, unresectable, locally advanced or metastatic liposarcoma (dedifferentiated, myxoid round cell, or pleomorphic) or leiomyosarcoma. Participants must have a pathology report indicating the diagnosis of liposarcoma or leiomyosarcoma that has been reviewed by the sponsor before randomization may occur
-
Treated in any order with at least: an anthracycline and ifosfamide containing regimen, or an anthracycline containing regimen and 1 additional cytotoxic chemotherapy regimen
-
Measurable disease at baseline in accordance with RECIST Version 1.1
-
Pathology specimens (example [e.g.], tumor blocks or unstained slides) for potential centralized pathology review and biomarker studies
-
ECOG Performance Status score of 0 or 1
-
Adequate recovery from prior therapy, all side effects (except alopecia) have resolved to Grade 1 or less according to the National Cancer Institute - Common Terminology Criteria of Adverse Events (NCI-CTCAE) Version 4.0
-
Adequate organ function as evidenced by the following peripheral blood counts or serum chemistry values: hemoglobin 9 gram per deciliters (g/dL), absolute neutrophil count (ANC) 1,500/L, platelet count 100,000/L, serum creatinine 1.5*the upper limit of normal (ULN), creatine phosphokinase (CPK) 2.5 Upper Limit of Normal [ULN]
-
Adequate hepatic function as evidenced by the following serum chemistry values: total bilirubin, ULN. If total bilirubin is greater than (>) ULN, measure indirect bilirubin to evaluate for Gilbert's syndrome (if direct bilirubin is within normal range, participant may be eligible) ALP 2.5 x ULN; Trabectedin: if the ALP is >2.5 x ULN, then an ALP liver fraction or 5-nucleotidase must be obtained and ULN, AST and ALT 2.5 ULN
-
Negative pregnancy test (urinary or serum beta-HCG) at screening (applicable to women of child bearing potential who are sexually active)
-
Female participants must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent (at the discretion of the investigator), or if sexually active, be practicing an effective method of birth control. Male participants must agree to use an adequate contraception method as deemed appropriate by the investigator (e.g., vasectomy, double-barrier, partner using effective contraception) and to not donate sperm for a minimum of 5 months after treatment discontinuation
Optional Extension Phase (OEP) Phase:
-
Documentation for inclusion criteria histologically proven, unresectable, locally advanced or metastatic liposarcoma (dedifferentiated, myxoid round cell, or pleomorphic) or leiomyosarcoma. Participants must have a pathology report indicating the diagnosis of liposarcoma or leiomyosarcoma that has been reviewed by the sponsor before randomization may occur and treated in any order with at least: an anthracycline and ifosfamide containing regimen, or an anthracycline containing regimen and 1 additional cytotoxic chemotherapy regimen do not need to be reviewed by the Sponsor
-
Collection of the specimen: Pathology specimens (example (e.g.), tumor blocks or unstained slides) for potential centralized pathology review and biomarker studies is not applicable
-
Documentation of inclusion criteria adequate organ function as evidenced by the following peripheral blood counts or serum chemistry values: hemoglobin 9 gram per deciliters (g/dL), absolute neutrophil count (ANC) 1,500/L, platelet count 100,000/L, serum creatinine 1.5the upper limit of normal (ULN), creatine phosphokinase (CPK) 2.5ULN and adequate hepatic function as evidenced by the following serum chemistry values: total bilirubin, ULN. If total bilirubin is greater than (>) ULN, measure indirect bilirubin to evaluate for Gilbert's syndrome (if direct bilirubin is within normal range, participant may be eligible) ALP <= 2.5*ULN; Trabectedin: if the ALP is
2.5*ULN, then an ALP liver fraction or 5-nucleotidase must be obtained and ULN, AST and ALT 2.5 ULN will be reviewed by the Sponsor before enrollment in the OEP may occur
Exclusion Criteria:
-
Potential participants who meet any of the following criteria will be excluded from participating in the study: Prior exposure to trabectedin or dacarabazine, less than 3 weeks from last dose of systemic cytotoxic therapy, radiation therapy, or therapy with any investigational agent, other malignancy within past 3 years. Exceptions: basal or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, or Federation Internationale de Gynecologie et d'Obstetrique (FIGO) Stage 1 carcinoma of the cervix
-
Known central nervous system metastasis
-
Known significant chronic liver disease, such as cirrhosis or active hepatitis (potential participants who test positive for hepatitis B surface antigen or hepatitis C antibodies are allowed provided they do not have active disease requiring antiviral therapy)
-
Myocardial infarct within 6 months before enrollment, New York Heart Association Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
-
Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, ongoing active infection, or psychiatric illness/social situation that may potentially impair the participant's compliance with study procedures
-
Unwilling or unable to have a central venous catheter
-
Known allergies, hypersensitivity, or intolerance to trabectedin, dacarbazine, dexamethasone, or their excipients
-
Pregnant or breast-feeding
-
Any condition that, in the opinion of the investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements
OEP phase:
-
Potential participants who meet any of the following criteria will be excluded from Participating in the study: Prior exposure to trabectedin, less than 3 weeks from last dose of systemic cytotoxic therapy, radiation therapy, or therapy with any investigational agent, other malignancy within past 3 years. Exceptions: basal or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, or Federation Internationale de Gynecologie et d'Obstetrique (FIGO) Stage 1 carcinoma of the cervix does not apply
-
Treated in any order with at least: an anthracycline and ifosfamide containing regimen, or an anthracycline containing regimen and 1 additional cytotoxic chemotherapy regimen with less than 3 weeks from last dose of systemic anticancer therapy, radiation therapy, or therapy with any investigational agent
-
Known allergies, hypersensitivity, or intolerance to dacarbazine does not apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Phoenix | Arizona | United States | ||
| 2 | Tucson | Arizona | United States | ||
| 3 | Little Rock | Arkansas | United States | ||
| 4 | La Jolla | California | United States | ||
| 5 | Los Angeles | California | United States | ||
| 6 | San Diego | California | United States | ||
| 7 | San Francisco | California | United States | ||
| 8 | Santa Monica | California | United States | ||
| 9 | Aurora | Colorado | United States | ||
| 10 | Denver | Colorado | United States | ||
| 11 | Hartford | Connecticut | United States | ||
| 12 | New Haven | Connecticut | United States | ||
| 13 | Boynton Beach | Florida | United States | ||
| 14 | Hollywood | Florida | United States | ||
| 15 | Miami | Florida | United States | ||
| 16 | Orlando | Florida | United States | ||
| 17 | Tampa | Florida | United States | ||
| 18 | Atlanta | Georgia | United States | ||
| 19 | Augusta | Georgia | United States | ||
| 20 | Savannah | Georgia | United States | ||
| 21 | Post Falls | Idaho | United States | ||
| 22 | Chicago | Illinois | United States | ||
| 23 | Naperville | Illinois | United States | ||
| 24 | Park Ridge | Illinois | United States | ||
| 25 | Peoria | Illinois | United States | ||
| 26 | Springfield | Illinois | United States | ||
| 27 | Indianapolis | Indiana | United States | ||
| 28 | Iowa City | Iowa | United States | ||
| 29 | Sioux City | Iowa | United States | ||
| 30 | Overland Park | Kansas | United States | ||
| 31 | Wichita | Kansas | United States | ||
| 32 | Louisville | Kentucky | United States | ||
| 33 | Covington | Louisiana | United States | ||
| 34 | Baltimore | Maryland | United States | ||
| 35 | Boston | Massachusetts | United States | ||
| 36 | Ann Arbor | Michigan | United States | ||
| 37 | Detroit | Michigan | United States | ||
| 38 | Lansing | Michigan | United States | ||
| 39 | Jackson | Mississippi | United States | ||
| 40 | Saint Joseph | Missouri | United States | ||
| 41 | Saint Louis | Missouri | United States | ||
| 42 | Omaha | Nebraska | United States | ||
| 43 | Henderson | Nevada | United States | ||
| 44 | Las Vegas | Nevada | United States | ||
| 45 | Lebanon | New Hampshire | United States | ||
| 46 | Hackensack | New Jersey | United States | ||
| 47 | Morristown | New Jersey | United States | ||
| 48 | Newark | New Jersey | United States | ||
| 49 | Albuquerque | New Mexico | United States | ||
| 50 | Bronx | New York | United States | ||
| 51 | Johnson City | New York | United States | ||
| 52 | New York | New York | United States | ||
| 53 | Syracuse | New York | United States | ||
| 54 | Chapel Hill | North Carolina | United States | ||
| 55 | Charlotte | North Carolina | United States | ||
| 56 | Akron | Ohio | United States | ||
| 57 | Cleveland | Ohio | United States | ||
| 58 | Columbus | Ohio | United States | ||
| 59 | Oklahoma City | Oklahoma | United States | ||
| 60 | Tulsa | Oklahoma | United States | ||
| 61 | Portland | Oregon | United States | ||
| 62 | Philadelphia | Pennsylvania | United States | ||
| 63 | Pittsburgh | Pennsylvania | United States | ||
| 64 | State College | Pennsylvania | United States | ||
| 65 | Charleston | South Carolina | United States | ||
| 66 | Knoxville | Tennessee | United States | ||
| 67 | Nashville | Tennessee | United States | ||
| 68 | Austin | Texas | United States | ||
| 69 | Dallas | Texas | United States | ||
| 70 | Houston | Texas | United States | ||
| 71 | San Antonio | Texas | United States | ||
| 72 | Salt Lake City | Utah | United States | ||
| 73 | Fairfax | Virginia | United States | ||
| 74 | Seattle | Washington | United States | ||
| 75 | Morgantown | West Virginia | United States | ||
| 76 | Green Bay | Wisconsin | United States | ||
| 77 | Milwaukee | Wisconsin | United States | ||
| 78 | Malvern | Australia | |||
| 79 | Randwick | Australia | |||
| 80 | Subiaco | Australia | |||
| 81 | Woolloongabba | Australia | |||
| 82 | Bahia | Brazil | |||
| 83 | Barretos | Brazil | |||
| 84 | Ijuà | Brazil | |||
| 85 | Porto Alegre | Brazil | |||
| 86 | Sao Paulo | Brazil | |||
| 87 | São Paulo | Brazil | |||
| 88 | Auckland | New Zealand | |||
| 89 | Wellington | New Zealand |
Sponsors and Collaborators
- Janssen Research & Development, LLC
- PharmaMar
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR018004
- ET743SAR3007
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Total enrolled participants were 577, but 2 participants were randomized twice, therefore counted twice in enrollment. Thus, enrolled participants are reported as 579. |
| Arm/Group Title | Trabectedin | Dacarbazine |
|---|---|---|
| Arm/Group Description | Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion. | Dacarbazine at a dose of 1 gram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion. |
| Period Title: Overall Study | ||
| STARTED | 384 | 193 |
| Treated | 378 | 172 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 384 | 193 |
Baseline Characteristics
| Arm/Group Title | Trabectedin | Dacarbazine | Total |
|---|---|---|---|
| Arm/Group Description | Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion. | Dacarbazine at a dose of 1 gram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion. | Total of all reporting groups |
| Overall Participants | 384 | 193 | 577 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
56.5
(11.04)
|
54.1
(11.92)
|
55.7
(11.39)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
262
68.2%
|
140
72.5%
|
402
69.7%
|
| Male |
122
31.8%
|
53
27.5%
|
175
30.3%
|
| Region of Enrollment (participants) [Number] | |||
| AUS |
15
3.9%
|
8
4.1%
|
23
4%
|
| BRA |
10
2.6%
|
2
1%
|
12
2.1%
|
| NZL |
3
0.8%
|
0
0%
|
3
0.5%
|
| USA |
356
92.7%
|
183
94.8%
|
539
93.4%
|
Outcome Measures
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | The Progression-Free Survival (PFS) was assessed as median number of months from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier. Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed. |
| Time Frame | approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all the randomized participants up to interim analysis cut-off date (16 September 2013). "N" (number of participants analyzed) signifies the participants evaluable for this measure. |
| Arm/Group Title | Trabectedin | Dacarbazine |
|---|---|---|
| Arm/Group Description | Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion. | Dacarbazine at a dose of 1 gram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion. |
| Measure Participants | 345 | 173 |
| Median (95% Confidence Interval) [Months] |
4.21
|
1.54
|
| Title | Time to Progression |
|---|---|
| Description | Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first. Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed. |
| Time Frame | approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all the randomized participants up to interim analysis cut-off date (16 September 2013). "N" (number of participants analyzed) signifies the participants evaluable for this measure. |
| Arm/Group Title | Trabectedin | Dacarbazine |
|---|---|---|
| Arm/Group Description | Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion. | Dacarbazine at a dose of 1 gram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion. |
| Measure Participants | 345 | 173 |
| Median (95% Confidence Interval) [Months] |
4.24
|
1.54
|
| Title | Objective Response Rate |
|---|---|
| Description | The objective response rate (ORR) is defined as the percentage of participants who achieved a Complete response (CR) or partial response (PR) as best responses. according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST). CR defined as disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of the diameters of the target lesions taking as reference the Baseline sum diameters. Confirmed responses are those that persist on repeat imaging study for at least 4 weeks after initial documentation of response. Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed. |
| Time Frame | approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all the randomized participants up to interim analysis cut-off date (16 September 2013). "N" (number of participants analyzed) signifies the participants evaluable for this measure. |
| Arm/Group Title | Trabectedin | Dacarbazine |
|---|---|---|
| Arm/Group Description | Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion. | Dacarbazine at a dose of 1 gram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion. |
| Measure Participants | 345 | 173 |
| Number (95% Confidence Interval) [Percentage of Participants] |
9.9
2.6%
|
6.9
3.6%
|
| Title | Duration of Response |
|---|---|
| Description | Duration of response is defined as the time from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death. Independent Data Monitoring Committee performed ongoing safety monitoring and conducted the interim analysis after 189 death events and 329 PFS events were observed. |
| Time Frame | approximately 2 years 4 months (From Study start date [27 May 2011] up to interim analysis data cut-off [16 September 2013]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all the randomized participants up to interim analysis cut-off date (16 September 2013). "N" (number of participants analyzed) signifies the participants evaluable for this measure. |
| Arm/Group Title | Trabectedin | Dacarbazine |
|---|---|---|
| Arm/Group Description | Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion. | Dacarbazine at a dose of 1 gram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion. |
| Measure Participants | 34 | 12 |
| Median (95% Confidence Interval) [Months] |
6.47
|
4.17
|
| Title | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Time Frame | approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all the treated participants. |
| Arm/Group Title | Trabectedin | Dacarbazine |
|---|---|---|
| Arm/Group Description | Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion. | Dacarbazine at a dose of 1 gram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion. |
| Measure Participants | 378 | 172 |
| Serious Adverse Events (SAEs) |
155
40.4%
|
52
26.9%
|
| Adverse Events (AEs) |
375
97.7%
|
166
86%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | The OS is defined as the time from the date of first dose of study drug to date of death from any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive. |
| Time Frame | approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all the randomized participants up to up to final analysis cut-off date (05 January 2015). |
| Arm/Group Title | Trabectedin | Dacarbazine |
|---|---|---|
| Arm/Group Description | Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion. | Dacarbazine at a dose of 1 gram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion. |
| Measure Participants | 384 | 193 |
| Median (95% Confidence Interval) [Months] |
13.73
|
13.14
|
Adverse Events
| Time Frame | approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015] | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population included all the treated participants. | |||
| Arm/Group Title | Trabectedin | Dacarbazine | ||
| Arm/Group Description | Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 24-hour every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each trabectedin infusion. | Dacarbazine at a dose of 1 gram per meter square (mg/m^2) was given as an intravenous (IV) infusion over 20-120 minutes every 3 weeks on Day 1 of every cycle (21 days) until disease progression. Dexamethasone 20 mg IV was also administered within 30 minutes before start of each dacarbazine infusion. | ||
All Cause Mortality |
||||
| Trabectedin | Dacarbazine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Trabectedin | Dacarbazine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 155/378 (41%) | 52/172 (30.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 15/378 (4%) | 4/172 (2.3%) | ||
| Febrile Neutropenia | 12/378 (3.2%) | 2/172 (1.2%) | ||
| Leukocytosis | 3/378 (0.8%) | 0/172 (0%) | ||
| Leukopenia | 4/378 (1.1%) | 3/172 (1.7%) | ||
| Microangiopathic Haemolytic Anaemia | 1/378 (0.3%) | 0/172 (0%) | ||
| Neutropenia | 9/378 (2.4%) | 1/172 (0.6%) | ||
| Thrombocytopenia | 7/378 (1.9%) | 3/172 (1.7%) | ||
| Cardiac disorders | ||||
| Atrial Fibrillation | 2/378 (0.5%) | 1/172 (0.6%) | ||
| Atrial Flutter | 1/378 (0.3%) | 0/172 (0%) | ||
| Cardiac Arrest | 3/378 (0.8%) | 0/172 (0%) | ||
| Cardiac Disorder | 1/378 (0.3%) | 0/172 (0%) | ||
| Cardiac Failure | 3/378 (0.8%) | 0/172 (0%) | ||
| Cardiac Failure Acute | 1/378 (0.3%) | 0/172 (0%) | ||
| Cardiac Failure Congestive | 7/378 (1.9%) | 0/172 (0%) | ||
| Cardiomyopathy | 2/378 (0.5%) | 0/172 (0%) | ||
| Left Ventricular Dysfunction | 1/378 (0.3%) | 0/172 (0%) | ||
| Palpitations | 1/378 (0.3%) | 0/172 (0%) | ||
| Right Ventricular Dysfunction | 1/378 (0.3%) | 0/172 (0%) | ||
| Sinus Tachycardia | 1/378 (0.3%) | 0/172 (0%) | ||
| Tachycardia | 1/378 (0.3%) | 1/172 (0.6%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 1/378 (0.3%) | 0/172 (0%) | ||
| Eye disorders | ||||
| Visual Impairment | 1/378 (0.3%) | 0/172 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Distension | 0/378 (0%) | 1/172 (0.6%) | ||
| Abdominal Hernia | 1/378 (0.3%) | 0/172 (0%) | ||
| Abdominal Pain | 13/378 (3.4%) | 8/172 (4.7%) | ||
| Abdominal Pain Lower | 2/378 (0.5%) | 1/172 (0.6%) | ||
| Abdominal Pain Upper | 1/378 (0.3%) | 0/172 (0%) | ||
| Ascites | 2/378 (0.5%) | 0/172 (0%) | ||
| Colitis | 2/378 (0.5%) | 0/172 (0%) | ||
| Constipation | 2/378 (0.5%) | 1/172 (0.6%) | ||
| Diarrhoea | 4/378 (1.1%) | 0/172 (0%) | ||
| Duodenal Obstruction | 1/378 (0.3%) | 2/172 (1.2%) | ||
| Dysphagia | 2/378 (0.5%) | 0/172 (0%) | ||
| Gastrointestinal Haemorrhage | 2/378 (0.5%) | 0/172 (0%) | ||
| Intestinal Obstruction | 3/378 (0.8%) | 0/172 (0%) | ||
| Intestinal Ulcer | 0/378 (0%) | 1/172 (0.6%) | ||
| Intra-Abdominal Haemorrhage | 1/378 (0.3%) | 0/172 (0%) | ||
| Large Intestinal Obstruction | 0/378 (0%) | 1/172 (0.6%) | ||
| Large Intestine Perforation | 1/378 (0.3%) | 0/172 (0%) | ||
| Lower Gastrointestinal Haemorrhage | 1/378 (0.3%) | 0/172 (0%) | ||
| Nausea | 15/378 (4%) | 3/172 (1.7%) | ||
| Obstruction Gastric | 1/378 (0.3%) | 1/172 (0.6%) | ||
| Oesophageal Obstruction | 1/378 (0.3%) | 0/172 (0%) | ||
| Oesophageal Pain | 1/378 (0.3%) | 0/172 (0%) | ||
| Pancreatitis | 3/378 (0.8%) | 0/172 (0%) | ||
| Rectal Haemorrhage | 1/378 (0.3%) | 0/172 (0%) | ||
| Small Intestinal Obstruction | 9/378 (2.4%) | 3/172 (1.7%) | ||
| Upper Gastrointestinal Haemorrhage | 1/378 (0.3%) | 0/172 (0%) | ||
| Vomiting | 15/378 (4%) | 3/172 (1.7%) | ||
| General disorders | ||||
| Asthenia | 5/378 (1.3%) | 0/172 (0%) | ||
| Catheter Site Inflammation | 1/378 (0.3%) | 0/172 (0%) | ||
| Chest Discomfort | 1/378 (0.3%) | 0/172 (0%) | ||
| Chest Pain | 1/378 (0.3%) | 0/172 (0%) | ||
| Death | 5/378 (1.3%) | 3/172 (1.7%) | ||
| Device Breakage | 1/378 (0.3%) | 0/172 (0%) | ||
| Device Failure | 1/378 (0.3%) | 0/172 (0%) | ||
| Fatigue | 4/378 (1.1%) | 1/172 (0.6%) | ||
| Gait Disturbance | 1/378 (0.3%) | 0/172 (0%) | ||
| Generalised Oedema | 1/378 (0.3%) | 0/172 (0%) | ||
| Infusion Site Extravasation | 2/378 (0.5%) | 0/172 (0%) | ||
| Malaise | 1/378 (0.3%) | 0/172 (0%) | ||
| Multi-Organ Failure | 1/378 (0.3%) | 0/172 (0%) | ||
| Necrosis | 1/378 (0.3%) | 0/172 (0%) | ||
| Non-Cardiac Chest Pain | 0/378 (0%) | 1/172 (0.6%) | ||
| Oedema Peripheral | 2/378 (0.5%) | 1/172 (0.6%) | ||
| Pain | 1/378 (0.3%) | 1/172 (0.6%) | ||
| Pyrexia | 12/378 (3.2%) | 2/172 (1.2%) | ||
| Thrombosis in Device | 1/378 (0.3%) | 0/172 (0%) | ||
| Hepatobiliary disorders | ||||
| Hepatotoxicity | 1/378 (0.3%) | 0/172 (0%) | ||
| Portal Vein Thrombosis | 1/378 (0.3%) | 0/172 (0%) | ||
| Immune system disorders | ||||
| Drug Hypersensitivity | 0/378 (0%) | 1/172 (0.6%) | ||
| Infections and infestations | ||||
| Appendicitis | 0/378 (0%) | 1/172 (0.6%) | ||
| Bacteraemia | 2/378 (0.5%) | 0/172 (0%) | ||
| Catheter Site Infection | 8/378 (2.1%) | 1/172 (0.6%) | ||
| Cellulitis | 2/378 (0.5%) | 0/172 (0%) | ||
| Clostridium Difficile Colitis | 1/378 (0.3%) | 0/172 (0%) | ||
| Clostridium Difficile Infection | 1/378 (0.3%) | 0/172 (0%) | ||
| Clostridium Difficile Sepsis | 1/378 (0.3%) | 0/172 (0%) | ||
| Enterococcal Bacteraemia | 1/378 (0.3%) | 0/172 (0%) | ||
| Kidney Infection | 1/378 (0.3%) | 0/172 (0%) | ||
| Lobar Pneumonia | 1/378 (0.3%) | 0/172 (0%) | ||
| Lung Infection | 2/378 (0.5%) | 0/172 (0%) | ||
| Osteomyelitis | 0/378 (0%) | 1/172 (0.6%) | ||
| Peritonitis | 0/378 (0%) | 1/172 (0.6%) | ||
| Pneumonia | 6/378 (1.6%) | 0/172 (0%) | ||
| Respiratory Tract Infection | 1/378 (0.3%) | 0/172 (0%) | ||
| Sepsis | 8/378 (2.1%) | 0/172 (0%) | ||
| Septic Shock | 2/378 (0.5%) | 0/172 (0%) | ||
| Staphylococcal Bacteraemia | 1/378 (0.3%) | 0/172 (0%) | ||
| Urinary Tract Infection | 7/378 (1.9%) | 2/172 (1.2%) | ||
| Urinary Tract Infection Staphylococcal | 1/378 (0.3%) | 0/172 (0%) | ||
| Vaginal Infection | 1/378 (0.3%) | 0/172 (0%) | ||
| Wound Abscess | 1/378 (0.3%) | 0/172 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Ankle Fracture | 1/378 (0.3%) | 0/172 (0%) | ||
| Fall | 2/378 (0.5%) | 0/172 (0%) | ||
| Post Procedural Haemorrhage | 1/378 (0.3%) | 0/172 (0%) | ||
| Vascular Access Complication | 1/378 (0.3%) | 0/172 (0%) | ||
| Wound | 1/378 (0.3%) | 0/172 (0%) | ||
| Investigations | ||||
| Alanine Aminotransferase Increased | 2/378 (0.5%) | 0/172 (0%) | ||
| Aspartate Aminotransferase Increased | 3/378 (0.8%) | 0/172 (0%) | ||
| Blood Bilirubin Increased | 0/378 (0%) | 1/172 (0.6%) | ||
| Blood Creatine Phosphokinase Increased | 4/378 (1.1%) | 0/172 (0%) | ||
| Blood Creatinine Increased | 4/378 (1.1%) | 0/172 (0%) | ||
| Blood Lactic Acid Increased | 0/378 (0%) | 1/172 (0.6%) | ||
| Ejection Fraction Decreased | 5/378 (1.3%) | 0/172 (0%) | ||
| International Normalised Ratio Increased | 2/378 (0.5%) | 0/172 (0%) | ||
| Liver Function Test Abnormal | 2/378 (0.5%) | 0/172 (0%) | ||
| Myoglobin Blood Increased | 1/378 (0.3%) | 0/172 (0%) | ||
| Neutrophil Count Decreased | 4/378 (1.1%) | 1/172 (0.6%) | ||
| Platelet Count Decreased | 4/378 (1.1%) | 2/172 (1.2%) | ||
| Transaminases Increased | 2/378 (0.5%) | 0/172 (0%) | ||
| Troponin I Increased | 2/378 (0.5%) | 0/172 (0%) | ||
| White Blood Cell Count Decreased | 2/378 (0.5%) | 0/172 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Acidosis | 1/378 (0.3%) | 0/172 (0%) | ||
| Decreased Appetite | 3/378 (0.8%) | 1/172 (0.6%) | ||
| Dehydration | 15/378 (4%) | 3/172 (1.7%) | ||
| Failure to Thrive | 2/378 (0.5%) | 0/172 (0%) | ||
| Fluid Overload | 1/378 (0.3%) | 0/172 (0%) | ||
| Fluid Retention | 1/378 (0.3%) | 1/172 (0.6%) | ||
| Hyperglycaemia | 0/378 (0%) | 1/172 (0.6%) | ||
| Hyperkalaemia | 2/378 (0.5%) | 0/172 (0%) | ||
| Hyperlipasaemia | 1/378 (0.3%) | 0/172 (0%) | ||
| Hypomagnesaemia | 1/378 (0.3%) | 0/172 (0%) | ||
| Hyponatraemia | 1/378 (0.3%) | 1/172 (0.6%) | ||
| Malnutrition | 1/378 (0.3%) | 0/172 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/378 (0.3%) | 0/172 (0%) | ||
| Back Pain | 3/378 (0.8%) | 2/172 (1.2%) | ||
| Bone Pain | 1/378 (0.3%) | 0/172 (0%) | ||
| Flank Pain | 0/378 (0%) | 1/172 (0.6%) | ||
| Joint Range of Motion Decreased | 1/378 (0.3%) | 0/172 (0%) | ||
| Joint Swelling | 1/378 (0.3%) | 0/172 (0%) | ||
| Neck Pain | 1/378 (0.3%) | 0/172 (0%) | ||
| Pain in Extremity | 2/378 (0.5%) | 2/172 (1.2%) | ||
| Rhabdomyolysis | 4/378 (1.1%) | 0/172 (0%) | ||
| Soft Tissue Necrosis | 1/378 (0.3%) | 0/172 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cancer Pain | 1/378 (0.3%) | 1/172 (0.6%) | ||
| Malignant Ascites | 0/378 (0%) | 1/172 (0.6%) | ||
| Tumour Pain | 1/378 (0.3%) | 3/172 (1.7%) | ||
| Nervous system disorders | ||||
| Cerebrovascular Accident | 2/378 (0.5%) | 0/172 (0%) | ||
| Dizziness | 1/378 (0.3%) | 0/172 (0%) | ||
| Haemorrhage Intracranial | 1/378 (0.3%) | 0/172 (0%) | ||
| Headache | 1/378 (0.3%) | 0/172 (0%) | ||
| Neuralgia | 0/378 (0%) | 2/172 (1.2%) | ||
| Pyramidal Tract Syndrome | 0/378 (0%) | 1/172 (0.6%) | ||
| Spinal Cord Compression | 1/378 (0.3%) | 2/172 (1.2%) | ||
| Syncope | 3/378 (0.8%) | 2/172 (1.2%) | ||
| Psychiatric disorders | ||||
| Confusional State | 3/378 (0.8%) | 0/172 (0%) | ||
| Mental Status Changes | 1/378 (0.3%) | 0/172 (0%) | ||
| Renal and urinary disorders | ||||
| Haematuria | 1/378 (0.3%) | 0/172 (0%) | ||
| Hydronephrosis | 1/378 (0.3%) | 1/172 (0.6%) | ||
| Obstructive Uropathy | 1/378 (0.3%) | 0/172 (0%) | ||
| Renal Failure | 1/378 (0.3%) | 0/172 (0%) | ||
| Renal Failure Acute | 12/378 (3.2%) | 1/172 (0.6%) | ||
| Renal Tubular Necrosis | 1/378 (0.3%) | 0/172 (0%) | ||
| Urinary Retention | 2/378 (0.5%) | 0/172 (0%) | ||
| Urinary Tract Obstruction | 1/378 (0.3%) | 0/172 (0%) | ||
| Reproductive system and breast disorders | ||||
| Pelvic Pain | 2/378 (0.5%) | 0/172 (0%) | ||
| Perineal Fistula | 1/378 (0.3%) | 0/172 (0%) | ||
| Vaginal Haemorrhage | 0/378 (0%) | 1/172 (0.6%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute Respiratory Failure | 1/378 (0.3%) | 0/172 (0%) | ||
| Bronchial Obstruction | 1/378 (0.3%) | 0/172 (0%) | ||
| Cough | 1/378 (0.3%) | 0/172 (0%) | ||
| Dyspnoea | 13/378 (3.4%) | 2/172 (1.2%) | ||
| Dyspnoea Exertional | 1/378 (0.3%) | 0/172 (0%) | ||
| Haemoptysis | 2/378 (0.5%) | 0/172 (0%) | ||
| Hypoxia | 2/378 (0.5%) | 0/172 (0%) | ||
| Pleural Effusion | 5/378 (1.3%) | 3/172 (1.7%) | ||
| Pleuritic Pain | 1/378 (0.3%) | 0/172 (0%) | ||
| Pneumonitis | 0/378 (0%) | 1/172 (0.6%) | ||
| Pneumothorax | 1/378 (0.3%) | 0/172 (0%) | ||
| Pulmonary Embolism | 6/378 (1.6%) | 1/172 (0.6%) | ||
| Pulmonary Hypertension | 2/378 (0.5%) | 0/172 (0%) | ||
| Pulmonary Oedema | 3/378 (0.8%) | 0/172 (0%) | ||
| Respiratory Arrest | 1/378 (0.3%) | 0/172 (0%) | ||
| Respiratory Distress | 1/378 (0.3%) | 0/172 (0%) | ||
| Respiratory Failure | 6/378 (1.6%) | 1/172 (0.6%) | ||
| Tachypnoea | 1/378 (0.3%) | 0/172 (0%) | ||
| Wheezing | 1/378 (0.3%) | 0/172 (0%) | ||
| Surgical and medical procedures | ||||
| Hip Surgery | 1/378 (0.3%) | 0/172 (0%) | ||
| Vascular disorders | ||||
| Circulatory Collapse | 0/378 (0%) | 1/172 (0.6%) | ||
| Deep Vein Thrombosis | 3/378 (0.8%) | 1/172 (0.6%) | ||
| Embolism | 1/378 (0.3%) | 0/172 (0%) | ||
| Embolism Venous | 1/378 (0.3%) | 0/172 (0%) | ||
| Hypotension | 4/378 (1.1%) | 1/172 (0.6%) | ||
| Jugular Vein Thrombosis | 1/378 (0.3%) | 0/172 (0%) | ||
| Temporal Arteritis | 0/378 (0%) | 1/172 (0.6%) | ||
| Venous Thrombosis | 1/378 (0.3%) | 0/172 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Trabectedin | Dacarbazine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 375/378 (99.2%) | 166/172 (96.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 149/378 (39.4%) | 48/172 (27.9%) | ||
| Leukopenia | 43/378 (11.4%) | 11/172 (6.4%) | ||
| Neutropenia | 111/378 (29.4%) | 31/172 (18%) | ||
| Thrombocytopenia | 70/378 (18.5%) | 33/172 (19.2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Distension | 30/378 (7.9%) | 16/172 (9.3%) | ||
| Abdominal Pain | 58/378 (15.3%) | 29/172 (16.9%) | ||
| Abdominal Pain Upper | 19/378 (5%) | 8/172 (4.7%) | ||
| Constipation | 140/378 (37%) | 52/172 (30.2%) | ||
| Diarrhoea | 130/378 (34.4%) | 40/172 (23.3%) | ||
| Dry Mouth | 22/378 (5.8%) | 13/172 (7.6%) | ||
| Dyspepsia | 30/378 (7.9%) | 12/172 (7%) | ||
| Gastrooesophageal Reflux Disease | 12/378 (3.2%) | 11/172 (6.4%) | ||
| Nausea | 282/378 (74.6%) | 85/172 (49.4%) | ||
| Stomatitis | 21/378 (5.6%) | 6/172 (3.5%) | ||
| Vomiting | 167/378 (44.2%) | 35/172 (20.3%) | ||
| General disorders | ||||
| Catheter Site Pain | 19/378 (5%) | 1/172 (0.6%) | ||
| Chest Pain | 19/378 (5%) | 6/172 (3.5%) | ||
| Chills | 34/378 (9%) | 11/172 (6.4%) | ||
| Fatigue | 260/378 (68.8%) | 90/172 (52.3%) | ||
| Influenza Like Illness | 19/378 (5%) | 6/172 (3.5%) | ||
| Oedema Peripheral | 107/378 (28.3%) | 21/172 (12.2%) | ||
| Pain | 18/378 (4.8%) | 9/172 (5.2%) | ||
| Pyrexia | 64/378 (16.9%) | 27/172 (15.7%) | ||
| Infections and infestations | ||||
| Upper Respiratory Tract Infection | 24/378 (6.3%) | 10/172 (5.8%) | ||
| Urinary Tract Infection | 29/378 (7.7%) | 8/172 (4.7%) | ||
| Investigations | ||||
| Alanine Aminotransferase Increased | 186/378 (49.2%) | 12/172 (7%) | ||
| Aspartate Aminotransferase Increased | 141/378 (37.3%) | 10/172 (5.8%) | ||
| Blood Alkaline Phosphatase Increased | 87/378 (23%) | 16/172 (9.3%) | ||
| Blood Bilirubin Increased | 34/378 (9%) | 5/172 (2.9%) | ||
| Blood Creatine Phosphokinase Increased | 54/378 (14.3%) | 2/172 (1.2%) | ||
| Blood Creatinine Increased | 47/378 (12.4%) | 3/172 (1.7%) | ||
| Lymphocyte Count Decreased | 21/378 (5.6%) | 4/172 (2.3%) | ||
| Neutrophil Count Decreased | 93/378 (24.6%) | 24/172 (14%) | ||
| Platelet Count Decreased | 61/378 (16.1%) | 29/172 (16.9%) | ||
| Weight Decreased | 27/378 (7.1%) | 5/172 (2.9%) | ||
| White Blood Cell Count Decreased | 96/378 (25.4%) | 20/172 (11.6%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 138/378 (36.5%) | 36/172 (20.9%) | ||
| Dehydration | 43/378 (11.4%) | 17/172 (9.9%) | ||
| Hyperglycaemia | 30/378 (7.9%) | 5/172 (2.9%) | ||
| Hypoalbuminaemia | 32/378 (8.5%) | 7/172 (4.1%) | ||
| Hypocalcaemia | 27/378 (7.1%) | 3/172 (1.7%) | ||
| Hypokalaemia | 53/378 (14%) | 22/172 (12.8%) | ||
| Hyponatraemia | 26/378 (6.9%) | 7/172 (4.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 57/378 (15.1%) | 15/172 (8.7%) | ||
| Back Pain | 65/378 (17.2%) | 28/172 (16.3%) | ||
| Bone Pain | 20/378 (5.3%) | 12/172 (7%) | ||
| Muscular Weakness | 25/378 (6.6%) | 4/172 (2.3%) | ||
| Musculoskeletal Pain | 29/378 (7.7%) | 14/172 (8.1%) | ||
| Myalgia | 47/378 (12.4%) | 11/172 (6.4%) | ||
| Pain in Extremity | 47/378 (12.4%) | 15/172 (8.7%) | ||
| Nervous system disorders | ||||
| Dizziness | 46/378 (12.2%) | 21/172 (12.2%) | ||
| Dysgeusia | 34/378 (9%) | 11/172 (6.4%) | ||
| Headache | 94/378 (24.9%) | 33/172 (19.2%) | ||
| Hypoaesthesia | 22/378 (5.8%) | 3/172 (1.7%) | ||
| Paraesthesia | 22/378 (5.8%) | 9/172 (5.2%) | ||
| Psychiatric disorders | ||||
| Anxiety | 40/378 (10.6%) | 13/172 (7.6%) | ||
| Depression | 30/378 (7.9%) | 7/172 (4.1%) | ||
| Insomnia | 55/378 (14.6%) | 16/172 (9.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 85/378 (22.5%) | 36/172 (20.9%) | ||
| Dyspnoea | 91/378 (24.1%) | 33/172 (19.2%) | ||
| Dyspnoea Exertional | 26/378 (6.9%) | 4/172 (2.3%) | ||
| Nasal Congestion | 23/378 (6.1%) | 6/172 (3.5%) | ||
| Oropharyngeal Pain | 19/378 (5%) | 4/172 (2.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 13/378 (3.4%) | 9/172 (5.2%) | ||
| Vascular disorders | ||||
| Flushing | 19/378 (5%) | 9/172 (5.2%) | ||
| Hot Flush | 13/378 (3.4%) | 10/172 (5.8%) | ||
| Hypertension | 22/378 (5.8%) | 2/172 (1.2%) | ||
| Hypotension | 19/378 (5%) | 7/172 (4.1%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
| Name/Title | Senior Director |
|---|---|
| Organization | Janssen Research & Development, LLC |
| Phone | |
| ClinicalTrialDisclosure@its.jnj.com |
- CR018004
- ET743SAR3007