A Study to Assess the Potential Effects of a Single-Dose Administration of Trabectedin on the QT Intervals of the Electrocardiogram

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00786838
• Collaborator: PharmaMar (Industry)
• Enrollment: 76
• Locations: 19
• Arm: 1
• Duration (Months): 14
• Patients Per Site: 4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the potential effects of trabectedin on the QT/QTc interval duration measured by electrocardiograms (ECGs) in participants with advanced solid tumor malignancies when administered at a therapeutic dose.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor	Drug: Trabectedin; Drug: Placebo	Phase 2

Detailed Description

This is a single-blind (where the participant does not know the treatment he receives), multicenter (study conducted at multiple sites), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study), sequential design (it is a design in a single group of Participants where one or more study medication is administered in a sequence) study to evaluate the potential effects of a single-dose administration of trabectedin on the QT intervals of the electrocardiogram (ECG). Initially, the study will consist of 2 phases: a screening phase (within 21 days before administration of the study medication), and a single-blind treatment phase (for 2 days). Participants who complete the single-blind treatment phase will be opted to take trabectedin in an open-label extension (for a minimum of 6 cycles), as long as they derive a clinical benefit (ie, until there is clear evidence of disease progression or unacceptable toxicity, as judged by the investigator). Participants will be assessed for ECG on predose before the single-blind treatment phase. During the single-blind treatment phase, a placebo control will be given on Day 1, and trabectedin (1.3 mg per square meter) will be administered on Day 2. Participants will be monitored until completion of the 24 hour pharmacokinetic blood sample collection. During the open-label extension (21 days after completion of the single-blind treatment phase), all Participants will receive trabectedin intravenously on Day 1 of each 17- to 49 day treatment cycle. The dose and schedule of trabectedin will be modified according to the type of malignancy being treated (ie, sarcoma, ovarian, or breast cancer). Safety evaluations will include assessment of adverse events, vital signs, physical examination, and clinical laboratory tests which will be performed throughout the study. The study duration for the open-label extension will vary by participant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Single-Blind, Multicenter, Placebo-Controlled, Sequential Design Study Evaluating the Potential Effects of a Single-Dose Administration of Trabectedin on the QT Intervals of the Electrocardiogram
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trabectedin 3-hour placebo intravenous infusion on Day 1 and trabectedin 1.3 mg/m2 3-hour intravenous infusion on Day 2 (single-blind). Patients may continue treatment with trabectedin until clinical benefit or drug is commercially available (open-label).	Drug: Trabectedin; Trabectedin will be administered as 1.3 mg/m2 3-hour intravenous infusion on Day 2.; Drug: Placebo; Participants will receive 3-hour placebo intravenous infusion on Day 1.

Outcome Measures

Primary Outcome Measures

1. The Difference in the Change From Baseline (Predose on Day 1) in QTc Intervals Trabectedin Relative to Placebo at 24 Hour Post Dose by Fridericia Correction [Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2)]

   QTc interval was measured by electrocardiograms to evaluate the potential effect of trabectedin on QTc interval duration. The Fridericia correction was used as the standard clinical correction for calculating the heart rate-corrected QT interval.

2. The Difference in the Change From Baseline (Predose on Day 1) in QTc Intervals Trabectedin Relative to Placebo at 24 Hour Post Dose by Bazett's Correction [Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2)]

   QTc interval was measured by electrocardiograms to evaluate the potential effect of trabectedin on QTc interval duration. The Bazett's Correction was used as the standard clinical correction for calculating the heart rate-corrected QT interval.

Secondary Outcome Measures

1. Maximum Plasma Concentration of Trabectedin (Cmax) [Baseline (predose on Day 2) to 24 hour post dose (Day 2 or Day 3).]

2. Time Taken to Acheive Maximum Plasma Concentration (Tmax) [Baseline (predose on Day 2) to 24 hour post dose (Day 2 or Day 3).]

3. Number of Participants With QTc Interval Increase From Baseline (Predose on Day 1) Greater Than 30 Milli Seconds [Baseline (predose) to approximately 24 hour post dose]

   The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.

4. Number of Participants With QTc Interval Increase From Baseline (Predose on Day 1) Greater Than 60 Milli Seconds [Baseline (predose) to approximately 24 hour post dose]

   The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.

5. Number of Participants With QTc Interval Greater Than 450 Milli Seconds [Baseline (predose) to approximately 24 hour post dose]

   The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.

6. Number of Participants With QTc Interval Greater Than 480 Milli Seconds [Baseline (predose) to approximately 24 hour post dose]

   The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QTc interval.

7. Number of Participants With QTc Interval Greater Than 500 Milli Seconds [Baseline (predose) to approximately 24 hour post dose]

   The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QTc interval.

8. Number of Participants With PR Interval Greater Than 200 Milli Seconds [Baseline (predose) to approximately 24 hour post dose]

   PR interval is the portion of the electrocardiogram between the onset of the P wave (atrial depolarization) and the QRS complex (ventricular depolarization).

9. Number of Participants With QRS Interval Greater Than 120 Milli Seconds [Baseline (predose) to approximately 24 hour post dose]

   QRS interval is the interval from the beginning of the Q wave to the termination of the S wave, representing the time for ventricular depolarization.

10. Mean Heart Rate (Beats Per Minute) Over 24 Hours Postdose [Baseline (predose on Day 1) to 24 hour post dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants with locally advanced or metastatic solid tumors who have received three or less prior lines of systemic chemotherapy

• Participants must have relapsed or had progressive disease following standard of care treatment with chemotherapy prior to enrollment, or intolerant to prior standard of care treatment with chemotherapy

• Normal cardiac conduction and function as documented on a 12-lead electrocardiogram

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1

• Adequate organ function as evidenced by laboratory tests

• Able to receive dexamethasone or its equivalent

• Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

• Participants treated with more than three prior chemotherapy regimens (including adjuvant therapy)

• Previous exposure to trabectedin

• Central nervous system (CNS) metastasis

• Known hypersensitivity to any of the components of the trabectedin intravenous formulation or dexamethasone

• Heart rhythm disturbances, unusual T wave and U wave (if present) morphology, blood pressure outside of normal range, a history of cardiac failure, myocardial infarction, or cardiomyopathy, or a history of additional risk factors for torsade de pointes (eg, heart failure, electrolyte abnormalities, family history of Long QT Syndrome)

• Participants who at screening are on medication that is known to prolong the QT interval or who is on CYP3A4 inhibitors or inducers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Miami	Florida	United States
2		Charlotte	North Carolina	United States
3		Philadelphia	Pennsylvania	United States
4		Tacoma	Washington	United States
5		Brussels		Belgium
6		Edegem		Belgium
7		Wilrijk		Belgium
8		Lyon		France
9		Marseille		France
10		Montpellier		France
11		Villejuif		France
12		Bangalore N/A		India
13		Pune		India
14		Seoul		Korea, Republic of
15		Moscow N/A		Russian Federation
16		Moscow		Russian Federation
17		St Petersburg N/A		Russian Federation
18		St-Petersburg		Russian Federation
19		Sanchinarro		Spain

Sponsors and Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• PharmaMar

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Placebo-Controlled Study Evaluating the Potential Effects of Trabectedin on the Heart in Patients with Advanced Cancer

Publications

None provided.

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT00786838
• Other Study ID Numbers: CR014917; ET743OVC1001
• First Posted: Nov 6, 2008
• Last Update Posted: Apr 11, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: Solid tumor; Advanced solid tumor; Malignant tumors; Sarcoma; Breast tumor; Ovarian tumor; QT interval; Trabectedin; Yondelis; Ecteinascidin 743; ET743
• Additional relevant MeSH terms: Trabectedin

Study Results

Participant Flow

Recruitment Details	This study was conducted in 7 countries: Belgium (3 sites), France (2 sites), India (2 sites), Republic of Korea (4 sites), Russia (4 sites), Spain (1 site), and the United States (4 sites). Total 75 participants were enrolled in this study.
Pre-assignment Detail	All enrolled participants (ie, 75 participants) received study medication. 26 participants completed the study.

Arm/Group Title	Trabectedin
Arm/Group Description	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Period Title: Overall Study
STARTED	75
COMPLETED	26
NOT COMPLETED	49

Baseline Characteristics

Arm/Group Title	Trabectedin
Arm/Group Description	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Overall Participants	75
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.2 (11.04)
Sex: Female, Male (Count of Participants)
Female	51 68%
Male	24 32%
Race/Ethnicity, Customized (participants) [Number]
White	51 68%
Asian	23 30.7%
Other	1 1.3%
Region of Enrollment (participants) [Number]
Belgium	17 22.7%
France	3 4%
India	8 10.7%
Republic Of Korea	15 20%
Russia	17 22.7%
Spain	4 5.3%
United States Of America	11 14.7%

Outcome Measures

1. Primary Outcome

Title	The Difference in the Change From Baseline (Predose on Day 1) in QTc Intervals Trabectedin Relative to Placebo at 24 Hour Post Dose by Fridericia Correction
Description	QTc interval was measured by electrocardiograms to evaluate the potential effect of trabectedin on QTc interval duration. The Fridericia correction was used as the standard clinical correction for calculating the heart rate-corrected QT interval.
Time Frame	Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2)

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Placebo	Trabectedin
Arm/Group Description	Placebo: Normal saline was administered as a 3-hour intravenous infusion on Day 1.	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2.
Measure Participants	74	74
Mean (Standard Deviation) [milli seconds]	3.6 (10.08)	-6.2 (10.65)

2. Secondary Outcome

Title	Maximum Plasma Concentration of Trabectedin (Cmax)
Time Frame	Baseline (predose on Day 2) to 24 hour post dose (Day 2 or Day 3).

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Trabectedin
Arm/Group Description	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Measure Participants	74
Mean (Standard Deviation) [nanogram per milliliter]	9.24 (3.75)

3. Secondary Outcome

Title	Time Taken to Acheive Maximum Plasma Concentration (Tmax)
Time Frame	Baseline (predose on Day 2) to 24 hour post dose (Day 2 or Day 3).

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Trabectedin
Arm/Group Description	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Measure Participants	74
Mean (Standard Deviation) [hours]	2.22 (0.65)

4. Secondary Outcome

Title	Number of Participants With QTc Interval Increase From Baseline (Predose on Day 1) Greater Than 30 Milli Seconds
Description	The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.
Time Frame	Baseline (predose) to approximately 24 hour post dose

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Placebo	Trabectedin
Arm/Group Description	Normal saline was administered as a 3-hour intravenous infusion on Day 1	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Measure Participants	74	74
QTcF greater than 30 milliseconds	2 2.7%	2 NaN
QTcB greater than 30 milliseconds	4 5.3%	6 NaN

5. Secondary Outcome

Title	Number of Participants With QTc Interval Increase From Baseline (Predose on Day 1) Greater Than 60 Milli Seconds
Description	The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.
Time Frame	Baseline (predose) to approximately 24 hour post dose

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Placebo	Trabectedin
Arm/Group Description	Normal saline was administered as a 3-hour intravenous infusion on Day 1	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Measure Participants	74	74
QTcF greater than 60 milliseconds	0 0%	0 NaN
QTcB greater than 60 milliseconds	0 0%	0 NaN

6. Secondary Outcome

Title	Number of Participants With QTc Interval Greater Than 450 Milli Seconds
Description	The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QT interval.
Time Frame	Baseline (predose) to approximately 24 hour post dose

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Placebo	Trabectedin
Arm/Group Description	Normal saline was administered as a 3-hour intravenous infusion on Day 1	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Measure Participants	74	74
QTcF greater than 450 milliseconds	6 8%	4 NaN
QTcB greater than 450 milliseconds	21 28%	23 NaN

7. Secondary Outcome

Title	Number of Participants With QTc Interval Greater Than 480 Milli Seconds
Description	The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QTc interval.
Time Frame	Baseline (predose) to approximately 24 hour post dose

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Placebo	Trabectedin
Arm/Group Description	Normal saline was administered as a 3-hour intravenous infusion on Day 1	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Measure Participants	74	74
QTcF greater than 480 milli seconds	0 0%	0 NaN
QTcB greater than 480 milli seconds	1 1.3%	2 NaN

8. Secondary Outcome

Title	Number of Participants With QTc Interval Greater Than 500 Milli Seconds
Description	The Fridericia (QTcF) and Bazett's (QTcB) correction were used as the standard clinical correction for calculating the heart rate-corrected QTc interval.
Time Frame	Baseline (predose) to approximately 24 hour post dose

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Placebo	Trabectedin
Arm/Group Description	Normal saline was administered as a 3-hour intravenous infusion on Day 1	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Measure Participants	74	74
QTcF greater than 500 milli seconds	0 0%	0 NaN
QTcB greater than 500 milli seconds	0 0%	0 NaN

9. Secondary Outcome

Title	Number of Participants With PR Interval Greater Than 200 Milli Seconds
Description	PR interval is the portion of the electrocardiogram between the onset of the P wave (atrial depolarization) and the QRS complex (ventricular depolarization).
Time Frame	Baseline (predose) to approximately 24 hour post dose

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Placebo	Trabectedin
Arm/Group Description	Normal saline was administered as a 3-hour intravenous infusion on Day 1	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Measure Participants	74	74
Number [participants]	3 4%	2 NaN

10. Secondary Outcome

Title	Number of Participants With QRS Interval Greater Than 120 Milli Seconds
Description	QRS interval is the interval from the beginning of the Q wave to the termination of the S wave, representing the time for ventricular depolarization.
Time Frame	Baseline (predose) to approximately 24 hour post dose

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Placebo	Trabectedin
Arm/Group Description	Normal saline was administered as a 3-hour intravenous infusion on Day 1	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Measure Participants	74	74
Number [participants]	1 1.3%	1 NaN

11. Secondary Outcome

Title	Mean Heart Rate (Beats Per Minute) Over 24 Hours Postdose
Time Frame	Baseline (predose on Day 1) to 24 hour post dose

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order was excluded from evaluations. 73 participants analyzed in trabectedin group to derive the mean.

Arm/Group Title	Placebo	Trabectedin
Arm/Group Description	Normal saline was administered as a 3-hour intravenous infusion on Day 1	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
Measure Participants	74	73
Mean (Standard Deviation) [beats per minute]	76.9 (10.51)	82.6 (11.13)

12. Primary Outcome

Title	The Difference in the Change From Baseline (Predose on Day 1) in QTc Intervals Trabectedin Relative to Placebo at 24 Hour Post Dose by Bazett's Correction
Description	QTc interval was measured by electrocardiograms to evaluate the potential effect of trabectedin on QTc interval duration. The Bazett's Correction was used as the standard clinical correction for calculating the heart rate-corrected QT interval.
Time Frame	Baseline (predose on Day 1) to 24 hour post dose (Day 1 or Day 2)

Outcome Measure Data

Analysis Population Description

All evaluable participants set: All participants who received placebo on Day 1 and trabectedin on Day 2 with atleast 1 paired predose and 1 paired postdose assessments. One participant who received study medication in reverse order (trabectedin and placebo were given on Days 1 and 2, respectively) was excluded from evaluations.

Arm/Group Title	Placebo	Trabectedin
Arm/Group Description	Normal saline was administered as a 3-hour intravenous infusion on Day 1.	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2.
Measure Participants	74	74
Mean (Standard Deviation) [milli seconds]	0.1 (10.15)	-1.5 (13.61)

Adverse Events

Time Frame	Until 30 days after the administration of the last dose of study medication
Adverse Event Reporting Description	Adverse events were reported for overall study.
Arm/Group Title	Trabectedin
Arm/Group Description	1.3 mg/m2 of trabectedin was administered as a 3-hour intravenous infusion on Day 2
All Cause Mortality
	Trabectedin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Trabectedin
	Affected / at Risk (%)	# Events
Total	31/75 (41.3%)
Blood and lymphatic system disorders
Anaemia	2/75 (2.7%)
Febrile bone marrow aplasia	1/75 (1.3%)
Febrile neutropenia	5/75 (6.7%)
Leukopenia	1/75 (1.3%)
Neutropenia	6/75 (8%)
Thrombocytopenia	4/75 (5.3%)
Gastrointestinal disorders
Abdominal pain	1/75 (1.3%)
Haematochezia	1/75 (1.3%)
Nausea	2/75 (2.7%)
Subileus	1/75 (1.3%)
Upper gastrointestinal haemorrhage	1/75 (1.3%)
Vomiting	4/75 (5.3%)
General disorders
Asthenia	4/75 (5.3%)
Disease progression	1/75 (1.3%)
Mucosal inflammation	1/75 (1.3%)
Pyrexia	4/75 (5.3%)
Hepatobiliary disorders
Hepatic function abnormal	2/75 (2.7%)
Hypertransaminasaemia	1/75 (1.3%)
Infections and infestations
Cellulitis	1/75 (1.3%)
Infection	1/75 (1.3%)
Oral fungal infection	1/75 (1.3%)
Sepsis	1/75 (1.3%)
Wound infection	1/75 (1.3%)
Injury, poisoning and procedural complications
Tibia fracture	1/75 (1.3%)
Metabolism and nutrition disorders
Anorexia	2/75 (2.7%)
Musculoskeletal and connective tissue disorders
Back pain	1/75 (1.3%)
Rhabdomyolysis	3/75 (4%)
Soft tissue haemorrhage	1/75 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm	1/75 (1.3%)
Bone sarcoma	1/75 (1.3%)
Oropharyngeal cancer stage unspecified	1/75 (1.3%)
Ovarian cancer	1/75 (1.3%)
Tumour haemorrhage	1/75 (1.3%)
Nervous system disorders
Syncope	1/75 (1.3%)
Renal and urinary disorders
Hydronephrosis	1/75 (1.3%)
Renal failure	2/75 (2.7%)
Renal impairment	1/75 (1.3%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/75 (1.3%)
Vascular disorders
Capillary leak syndrome	1/75 (1.3%)
Embolism	1/75 (1.3%)
Iliac artery occlusion	1/75 (1.3%)
Vena cava thrombosis	1/75 (1.3%)
Other (Not Including Serious) Adverse Events
	Trabectedin
	Affected / at Risk (%)	# Events
Total	70/75 (93.3%)
Blood and lymphatic system disorders
Anaemia	22/75 (29.3%)
Leukopenia	9/75 (12%)
Neutropenia	31/75 (41.3%)
Thrombocytopenia	13/75 (17.3%)
Gastrointestinal disorders
Abdominal pain	5/75 (6.7%)
Abdominal pain upper	4/75 (5.3%)
Constipation	8/75 (10.7%)
Diarrhoea	5/75 (6.7%)
Nausea	38/75 (50.7%)
Vomiting	30/75 (40%)
General disorders
Asthenia	24/75 (32%)
Fatigue	17/75 (22.7%)
Oedema peripheral	4/75 (5.3%)
Pain	4/75 (5.3%)
Pyrexia	8/75 (10.7%)
Hepatobiliary disorders
Hepatic function abnormal	33/75 (44%)
Metabolism and nutrition disorders
Anorexia	16/75 (21.3%)
Enzyme abnormality	8/75 (10.7%)
Hypocalcaemia	6/75 (8%)
Musculoskeletal and connective tissue disorders
Myalgia	4/75 (5.3%)
Nervous system disorders
Dizziness	12/75 (16%)
Respiratory, thoracic and mediastinal disorders
Cough	8/75 (10.7%)
Dyspnoea	5/75 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.