A Study Comparing the Combination of Trabectedin (YONDELIS) and DOXIL/CAELYX With DOXIL/CAELYX for the Treatment of Advanced-Relapsed Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

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ClinicalTrials.gov Identifier: NCT01846611

Recruitment Status : Completed

First Posted : May 3, 2013

Results First Posted : February 6, 2019

Last Update Posted : April 1, 2019

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Sponsor:

Collaborator:

PharmaMar

Information provided by (Responsible Party):

Janssen Research & Development, LLC

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Ovarian Neoplasms Peritoneal Neoplasms Fallopian Tube Neoplasms
Interventions	Drug: Trabectedin Drug: DOXIL Drug: Dexamethasone
Enrollment	581

Participant Flow

Recruitment Details
Pre-assignment Details	Total 581 participants were enrolled. Out of which 5 participants who were enrolled at the time of study termination were not assigned to any treatment group. Therefore, these 5 participants were not considered as randomized participants and excluded from result analysis.


Arm/Group Title	Trabectedin + DOXIL	DOXIL
Arm/Group Description	Participants received DOXIL 30 mill...	Participants received DOXIL 50 mg/m...
Arm/Group Description	Participants received DOXIL 30 milligram per meter square (mg/m^2) administered as an intravenous (IV) infusion over approximately 90 minutes followed by trabectedin 1.1 mg/m^2 administered as an IV infusion over approximately 3 hours, on Day 1 of each treatment cycle (21 days cycle) every 3 weeks. Participants were pretreated with 20 mg dexamethasone IV (or an equivalent IV corticosteroid) approximately 30 minutes prior to initiation of infusion of DOXIL IV.	Participants received DOXIL 50 mg/m^2 administered as an IV infusion over approximately 90 minutes on Day 1 of each treatment cycle (28 days cycle), every 4 weeks.
Period Title: Overall Study
Started	289	287
Treated	286	282
Completed	251	244
Not Completed	38	43
Reason Not Completed
Lost to Follow-up	4	6
Withdrawal by Subject	15	19
Other	19	18

Baseline Characteristics

Arm/Group Title		Trabectedin + DOXIL	DOXIL	Total
Arm/Group Description		Participants received DOXIL 30 mill...	Participants received DOXIL 50 mg/m...	Total of all reporting groups
Arm/Group Description		Participants received DOXIL 30 milligram per meter square (mg/m^2) administered as an intravenous (IV) infusion over approximately 90 minutes followed by trabectedin 1.1 mg/m^2 administered as an IV infusion over approximately 3 hours, on Day 1 of each treatment cycle (21 days cycle) every 3 weeks. Participants were pretreated with 20 mg dexamethasone IV (or an equivalent IV corticosteroid) approximately 30 minutes prior to initiation of infusion of DOXIL IV.	Participants received DOXIL 50 mg/m^2 administered as an IV infusion over approximately 90 minutes on Day 1 of each treatment cycle (28 days cycle), every 4 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		289	287	576
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	289 participants	287 participants	576 participants
		59.8 (10.16)	59.9 (10.35)	59.9 (10.25)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	289 participants	287 participants	576 participants
	Female	289 100.0%	287 100.0%	576 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	289 participants	287 participants	576 participants
	Hispanic or Latino	10 3.5%	5 1.7%	15 2.6%
	Not Hispanic or Latino	270 93.4%	278 96.9%	548 95.1%
	Unknown or Not Reported	9 3.1%	4 1.4%	13 2.3%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	289 participants	287 participants	576 participants
Asian		15 5.2%	23 8.0%	38 6.6%
Black or African American		3 1.0%	4 1.4%	7 1.2%
Hispanic or Latino		8 2.8%	3 1.0%	11 1.9%
Other		15 5.2%	11 3.8%	26 4.5%
White Non-Hispanic		248 85.8%	246 85.7%	494 85.8%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	289 participants	287 participants	576 participants
AUSTRALIA		15 5.2%	14 4.9%	29 5.0%
CHINA		9 3.1%	18 6.3%	27 4.7%
ISRAEL		2 0.7%	8 2.8%	10 1.7%
NEW ZEALAND		10 3.5%	8 2.8%	18 3.1%
POLAND		3 1.0%	5 1.7%	8 1.4%
RUSSIAN FEDERATION		124 42.9%	122 42.5%	246 42.7%
SOUTH AFRICA		7 2.4%	4 1.4%	11 1.9%
SWITZERLAND		1 0.3%	0 0.0%	1 0.2%
UNITED KINGDOM		15 5.2%	7 2.4%	22 3.8%
UNITED STATES		103 35.6%	101 35.2%	204 35.4%

Outcome Measures

1.Primary Outcome


Title	Overall Survival (OS)
Description	OS is defined as the time between the date of randomization and the da...
Description	OS is defined as the time between the date of randomization and the date of death. Participants who died, regardless of the cause of death, were considered to have had an event.
Time Frame	Up to 4.3 years

Outcome Measure Data

Analysis Population Description

All randomized analysis set included all participants who were randomized to study treatment independent of whether they received study drug.


Arm/Group Title	Trabectedin + DOXIL	DOXIL
Arm/Group Description:	Participants received DOXIL 30 mill...	Participants received DOXIL 50 mg/m...
Arm/Group Description:	Participants received DOXIL 30 milligram per meter square (mg/m^2) administered as an intravenous (IV) infusion over approximately 90 minutes followed by trabectedin 1.1 mg/m^2 administered as an IV infusion over approximately 3 hours, on Day 1 of each treatment cycle (21 days cycle) every 3 weeks. Participants were pretreated with 20 mg dexamethasone IV (or an equivalent IV corticosteroid) approximately 30 minutes prior to initiation of infusion of DOXIL IV.	Participants received DOXIL 50 mg/m^2 administered as an IV infusion over approximately 90 minutes on Day 1 of each treatment cycle (28 days cycle), every 4 weeks.
Overall Number of Participants Analyzed	289	287
Median (95% Confidence Interval) Unit of Measure: months
	23.82 (20.30 to 26.12)	22.21 (18.10 to 24.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Trabectedin + DOXIL, DOXIL
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	= 0.5236
	Comments	[Not Specified]
	Method	Unstratified log rank test
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.925
	Confidence Interval	(2-Sided) 95% 0.727 to 1.177
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Progression-Free Survival (PFS)
Description	PFS is defined as the time between the date of randomization and the d...
Description	PFS is defined as the time between the date of randomization and the date of disease progression or death. PFS was assessed using the response evaluation criteria in solid tumors (RECIST) Version 1.1. As per criteria progressive disease in case of target lesions means at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Progressive disease in case of non-target lesions means unequivocal progression of existing non-target lesions. In both cases the appearance of one or more new lesions is also considered progression.
Time Frame	Up to 4.3 years

Outcome Measure Data

Analysis Population Description

All randomized analysis set included all participants who were randomized to study treatment independent of whether they received study drug.


Arm/Group Title	Trabectedin + DOXIL	DOXIL
Arm/Group Description:	Participants received DOXIL 30 mill...	Participants received DOXIL 50 mg/m...
Arm/Group Description:	Participants received DOXIL 30 milligram per meter square (mg/m^2) administered as an intravenous (IV) infusion over approximately 90 minutes followed by trabectedin 1.1 mg/m^2 administered as an IV infusion over approximately 3 hours, on Day 1 of each treatment cycle (21 days cycle) every 3 weeks. Participants were pretreated with 20 mg dexamethasone IV (or an equivalent IV corticosteroid) approximately 30 minutes prior to initiation of infusion of DOXIL IV.	Participants received DOXIL 50 mg/m^2 administered as an IV infusion over approximately 90 minutes on Day 1 of each treatment cycle (28 days cycle), every 4 weeks.
Overall Number of Participants Analyzed	289	287
Median (95% Confidence Interval) Unit of Measure: months
	7.52 (6.93 to 9.43)	7.26 (6.14 to 7.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Trabectedin + DOXIL, DOXIL
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	= 0.5174
	Comments	[Not Specified]
	Method	Unstratified log rank test
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.935
	Confidence Interval	(2-Sided) 95% 0.762 to 1.147
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Objective Response Rate (ORR)
Description	ORR is defined as the percentage of participants with measurable disea...
Description	ORR is defined as the percentage of participants with measurable disease achieving a best overall response of either complete response (CR) or partial response (PR) based on RECIST. CR: disappearance of all target and non-target lesions and normalization of tumor marker levels in non-target lesions. PR: at least a 30 percent (%) decrease in the sum of longest diameter (LD) of target lesions or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
Time Frame	Up to 4.3 years

Outcome Measure Data

Analysis Population Description

All randomized analysis set included all participants who were randomized to study treatment independent of whether they received study drug.


Arm/Group Title	Trabectedin + DOXIL	DOXIL
Arm/Group Description:	Participants received DOXIL 30 mill...	Participants received DOXIL 50 mg/m...
Arm/Group Description:	Participants received DOXIL 30 milligram per meter square (mg/m^2) administered as an intravenous (IV) infusion over approximately 90 minutes followed by trabectedin 1.1 mg/m^2 administered as an IV infusion over approximately 3 hours, on Day 1 of each treatment cycle (21 days cycle) every 3 weeks. Participants were pretreated with 20 mg dexamethasone IV (or an equivalent IV corticosteroid) approximately 30 minutes prior to initiation of infusion of DOXIL IV.	Participants received DOXIL 50 mg/m^2 administered as an IV infusion over approximately 90 minutes on Day 1 of each treatment cycle (28 days cycle), every 4 weeks.
Overall Number of Participants Analyzed	289	287
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of participants
	46.0 (40.2 to 52.0)	35.9 (30.3 to 41.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Trabectedin + DOXIL, DOXIL
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	= 0.0142
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.523
	Confidence Interval	(2-Sided) 95% 1.075 to 2.158
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Up to 4.3 years
Adverse Event Reporting Description	Safety population included all-treated participants who received at least 1 dose of study drug.

Arm/Group Title	Trabectedin + DOXIL	DOXIL
Arm/Group Description	Participants received DOXIL 30 mill...	Participants received DOXIL 50 mg/m...
Arm/Group Description	Participants received DOXIL 30 milligram per meter square (mg/m^2) administered as an intravenous (IV) infusion over approximately 90 minutes followed by trabectedin 1.1 mg/m^2 administered as an IV infusion over approximately 3 hours, on Day 1 of each treatment cycle (21 days cycle) every 3 weeks. Participants were pretreated with 20 mg dexamethasone IV (or an equivalent IV corticosteroid) approximately 30 minutes prior to initiation of infusion of DOXIL IV.	Participants received DOXIL 50 mg/m^2 administered as an IV infusion over approximately 90 minutes on Day 1 of each treatment cycle (28 days cycle), every 4 weeks.
All-Cause Mortality
	Trabectedin + DOXIL	DOXIL
	Affected / at Risk (%)	Affected / at Risk (%)
Total	132/286 (46.15%)	131/282 (46.45%)
Serious Adverse Events Serious Adverse Events
	Trabectedin + DOXIL	DOXIL
	Affected / at Risk (%)	Affected / at Risk (%)
Total	118/286 (41.26%)	58/282 (20.57%)
Blood and lymphatic system disorders
Anaemia ^* 1	9/286 (3.15%)	2/282 (0.71%)
Febrile Neutropenia ^* 1	14/286 (4.90%)	1/282 (0.35%)
Leukopenia ^* 1	3/286 (1.05%)	1/282 (0.35%)
Neutropenia ^* 1	12/286 (4.20%)	4/282 (1.42%)
Thrombocytopenia ^* 1	10/286 (3.50%)	1/282 (0.35%)
Cardiac disorders
Atrial Fibrillation ^* 1	1/286 (0.35%)	1/282 (0.35%)
Cardiac Failure Congestive ^* 1	1/286 (0.35%)	0/282 (0.00%)
Cardiopulmonary Failure ^* 1	1/286 (0.35%)	0/282 (0.00%)
Tachycardia ^* 1	1/286 (0.35%)	0/282 (0.00%)
Endocrine disorders
Inappropriate Antidiuretic Hormone Secretion ^* 1	1/286 (0.35%)	0/282 (0.00%)
Gastrointestinal disorders
Abdominal Pain ^* 1	6/286 (2.10%)	3/282 (1.06%)
Abdominal Pain Lower ^* 1	0/286 (0.00%)	1/282 (0.35%)
Abdominal Pain Upper ^* 1	1/286 (0.35%)	0/282 (0.00%)
Ascites ^* 1	3/286 (1.05%)	8/282 (2.84%)
Constipation ^* 1	5/286 (1.75%)	2/282 (0.71%)
Diarrhoea ^* 1	2/286 (0.70%)	0/282 (0.00%)
Dyspepsia ^* 1	1/286 (0.35%)	0/282 (0.00%)
Enteritis ^* 1	1/286 (0.35%)	0/282 (0.00%)
Gastrointestinal Haemorrhage ^* 1	1/286 (0.35%)	0/282 (0.00%)
Gastrointestinal Obstruction ^* 1	1/286 (0.35%)	0/282 (0.00%)
Gastrooesophageal Reflux Disease ^* 1	0/286 (0.00%)	1/282 (0.35%)
Ileus ^* 1	0/286 (0.00%)	3/282 (1.06%)
Intestinal Obstruction ^* 1	3/286 (1.05%)	1/282 (0.35%)
Nausea ^* 1	8/286 (2.80%)	3/282 (1.06%)
Neutropenic Colitis ^* 1	0/286 (0.00%)	1/282 (0.35%)
Oral Pain ^* 1	0/286 (0.00%)	1/282 (0.35%)
Oral Pruritus ^* 1	0/286 (0.00%)	1/282 (0.35%)
Pancreatitis ^* 1	1/286 (0.35%)	0/282 (0.00%)
Rectal Haemorrhage ^* 1	1/286 (0.35%)	0/282 (0.00%)
Small Intestinal Obstruction ^* 1	4/286 (1.40%)	14/282 (4.96%)
Stomatitis ^* 1	0/286 (0.00%)	2/282 (0.71%)
Subileus ^* 1	1/286 (0.35%)	0/282 (0.00%)
Upper Gastrointestinal Haemorrhage ^* 1	1/286 (0.35%)	0/282 (0.00%)
Vomiting ^* 1	10/286 (3.50%)	7/282 (2.48%)
General disorders
Asthenia ^* 1	0/286 (0.00%)	1/282 (0.35%)
Catheter Site Inflammation ^* 1	1/286 (0.35%)	0/282 (0.00%)
Chest Discomfort ^* 1	0/286 (0.00%)	1/282 (0.35%)
Chest Pain ^* 1	0/286 (0.00%)	1/282 (0.35%)
Death ^* 1	4/286 (1.40%)	2/282 (0.71%)
Fatigue ^* 1	4/286 (1.40%)	1/282 (0.35%)
Influenza Like Illness ^* 1	1/286 (0.35%)	0/282 (0.00%)
Multiple Organ Dysfunction Syndrome ^* 1	2/286 (0.70%)	1/282 (0.35%)
Oedema Peripheral ^* 1	1/286 (0.35%)	0/282 (0.00%)
Pain ^* 1	0/286 (0.00%)	1/282 (0.35%)
Pyrexia ^* 1	9/286 (3.15%)	3/282 (1.06%)
Hepatobiliary disorders
Drug-Induced Liver Injury ^* 1	1/286 (0.35%)	0/282 (0.00%)
Hepatitis Toxic ^* 1	2/286 (0.70%)	0/282 (0.00%)
Infections and infestations
Abdominal Wall Abscess ^* 1	0/286 (0.00%)	1/282 (0.35%)
Catheter Site Infection ^* 1	0/286 (0.00%)	1/282 (0.35%)
Cellulitis ^* 1	2/286 (0.70%)	1/282 (0.35%)
Device Related Infection ^* 1	3/286 (1.05%)	1/282 (0.35%)
Device Related Sepsis ^* 1	1/286 (0.35%)	0/282 (0.00%)
Enterobacter Bacteraemia ^* 1	1/286 (0.35%)	0/282 (0.00%)
Gastroenteritis ^* 1	0/286 (0.00%)	1/282 (0.35%)
Infection ^* 1	1/286 (0.35%)	0/282 (0.00%)
Neutropenic Sepsis ^* 1	2/286 (0.70%)	1/282 (0.35%)
Oral Candidiasis ^* 1	0/286 (0.00%)	1/282 (0.35%)
Peritonitis ^* 1	2/286 (0.70%)	0/282 (0.00%)
Peritonitis Bacterial ^* 1	1/286 (0.35%)	0/282 (0.00%)
Pneumocystis Jirovecii Pneumonia ^* 1	2/286 (0.70%)	1/282 (0.35%)
Pneumonia ^* 1	4/286 (1.40%)	0/282 (0.00%)
Pseudomonal Sepsis ^* 1	1/286 (0.35%)	0/282 (0.00%)
Pyelonephritis Acute ^* 1	0/286 (0.00%)	1/282 (0.35%)
Sepsis ^* 1	4/286 (1.40%)	2/282 (0.71%)
Septic Shock ^* 1	1/286 (0.35%)	0/282 (0.00%)
Soft Tissue Infection ^* 1	1/286 (0.35%)	0/282 (0.00%)
Staphylococcal Bacteraemia ^* 1	1/286 (0.35%)	0/282 (0.00%)
Upper Respiratory Tract Infection ^* 1	1/286 (0.35%)	0/282 (0.00%)
Urinary Tract Infection ^* 1	5/286 (1.75%)	1/282 (0.35%)
Injury, poisoning and procedural complications
Anastomotic Ulcer ^* 1	1/286 (0.35%)	0/282 (0.00%)
Gastrointestinal Stoma Complication ^* 1	1/286 (0.35%)	0/282 (0.00%)
Head Injury ^* 1	0/286 (0.00%)	1/282 (0.35%)
Hip Fracture ^* 1	1/286 (0.35%)	0/282 (0.00%)
Infusion Related Reaction ^* 1	0/286 (0.00%)	2/282 (0.71%)
Joint Dislocation ^* 1	0/286 (0.00%)	1/282 (0.35%)
Spinal Compression Fracture ^* 1	1/286 (0.35%)	0/282 (0.00%)
Investigations
Alanine Aminotransferase Increased ^* 1	14/286 (4.90%)	0/282 (0.00%)
Aspartate Aminotransferase Increased ^* 1	9/286 (3.15%)	0/282 (0.00%)
Blood Creatine Phosphokinase Increased ^* 1	1/286 (0.35%)	0/282 (0.00%)
Blood Creatinine Increased ^* 1	1/286 (0.35%)	0/282 (0.00%)
Ejection Fraction Decreased ^* 1	2/286 (0.70%)	1/282 (0.35%)
Gamma-Glutamyltransferase Increased ^* 1	1/286 (0.35%)	0/282 (0.00%)
Neutrophil Count Decreased ^* 1	5/286 (1.75%)	0/282 (0.00%)
Platelet Count Decreased ^* 1	3/286 (1.05%)	0/282 (0.00%)
Transaminases Increased ^* 1	1/286 (0.35%)	0/282 (0.00%)
Weight Decreased ^* 1	1/286 (0.35%)	0/282 (0.00%)
White Blood Cell Count Decreased ^* 1	4/286 (1.40%)	0/282 (0.00%)
Metabolism and nutrition disorders
Dehydration ^* 1	6/286 (2.10%)	0/282 (0.00%)
Fluid Overload ^* 1	1/286 (0.35%)	0/282 (0.00%)
Hyperkalaemia ^* 1	1/286 (0.35%)	0/282 (0.00%)
Hypokalaemia ^* 1	1/286 (0.35%)	1/282 (0.35%)
Hyponatraemia ^* 1	2/286 (0.70%)	0/282 (0.00%)
Hypophagia ^* 1	0/286 (0.00%)	1/282 (0.35%)
Musculoskeletal and connective tissue disorders
Back Pain ^* 1	1/286 (0.35%)	1/282 (0.35%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphangiosis Carcinomatosa ^* 1	1/286 (0.35%)	0/282 (0.00%)
Malignant Pleural Effusion ^* 1	0/286 (0.00%)	1/282 (0.35%)
Metastases to Abdominal Wall ^* 1	0/286 (0.00%)	1/282 (0.35%)
Metastases to Central Nervous System ^* 1	0/286 (0.00%)	1/282 (0.35%)
Myelodysplastic Syndrome ^* 1	1/286 (0.35%)	0/282 (0.00%)
Renal Cell Carcinoma ^* 1	0/286 (0.00%)	1/282 (0.35%)
Nervous system disorders
Headache ^* 1	0/286 (0.00%)	1/282 (0.35%)
Lethargy ^* 1	1/286 (0.35%)	0/282 (0.00%)
Seizure ^* 1	1/286 (0.35%)	1/282 (0.35%)
Syncope ^* 1	1/286 (0.35%)	0/282 (0.00%)
Product Issues
Device Malfunction ^* 1	0/286 (0.00%)	1/282 (0.35%)
Renal and urinary disorders
Acute Kidney Injury ^* 1	4/286 (1.40%)	2/282 (0.71%)
Renal Failure ^* 1	1/286 (0.35%)	1/282 (0.35%)
Urinary Retention ^* 1	0/286 (0.00%)	1/282 (0.35%)
Reproductive system and breast disorders
Pelvic Fluid Collection ^* 1	0/286 (0.00%)	1/282 (0.35%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure ^* 1	1/286 (0.35%)	0/282 (0.00%)
Chronic Obstructive Pulmonary Disease ^* 1	1/286 (0.35%)	0/282 (0.00%)
Cough ^* 1	1/286 (0.35%)	0/282 (0.00%)
Dyspnoea ^* 1	1/286 (0.35%)	1/282 (0.35%)
Epistaxis ^* 1	1/286 (0.35%)	0/282 (0.00%)
Hypoxia ^* 1	2/286 (0.70%)	0/282 (0.00%)
Interstitial Lung Disease ^* 1	0/286 (0.00%)	1/282 (0.35%)
Pleural Effusion ^* 1	4/286 (1.40%)	2/282 (0.71%)
Pleurisy ^* 1	2/286 (0.70%)	2/282 (0.71%)
Pulmonary Embolism ^* 1	6/286 (2.10%)	2/282 (0.71%)
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome ^* 1	0/286 (0.00%)	1/282 (0.35%)
Vascular disorders
Capillary Leak Syndrome ^* 1	0/286 (0.00%)	1/282 (0.35%)
Deep Vein Thrombosis ^* 1	3/286 (1.05%)	0/282 (0.00%)
Embolism ^* 1	1/286 (0.35%)	0/282 (0.00%)
Flushing ^* 1	0/286 (0.00%)	1/282 (0.35%)
Hypertension ^* 1	0/286 (0.00%)	1/282 (0.35%)
Pelvic Venous Thrombosis ^* 1	1/286 (0.35%)	0/282 (0.00%)
Thrombophlebitis ^* 1	2/286 (0.70%)	0/282 (0.00%)
1 Term from vocabulary, MedDRA Version 19.0 * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Trabectedin + DOXIL	DOXIL
	Affected / at Risk (%)	Affected / at Risk (%)
Total	282/286 (98.60%)	273/282 (96.81%)
Blood and lymphatic system disorders
Anaemia ^* 1	135/286 (47.20%)	70/282 (24.82%)
Febrile Neutropenia ^* 1	9/286 (3.15%)	2/282 (0.71%)
Leukopenia ^* 1	53/286 (18.53%)	38/282 (13.48%)
Neutropenia ^* 1	149/286 (52.10%)	104/282 (36.88%)
Thrombocytopenia ^* 1	63/286 (22.03%)	18/282 (6.38%)
Cardiac disorders
Palpitations ^* 1	7/286 (2.45%)	6/282 (2.13%)
Tachycardia ^* 1	9/286 (3.15%)	2/282 (0.71%)
Ear and labyrinth disorders
Vertigo ^* 1	6/286 (2.10%)	6/282 (2.13%)
Gastrointestinal disorders
Abdominal Distension ^* 1	20/286 (6.99%)	15/282 (5.32%)
Abdominal Pain ^* 1	54/286 (18.88%)	44/282 (15.60%)
Abdominal Pain Lower ^* 1	6/286 (2.10%)	7/282 (2.48%)
Abdominal Pain Upper ^* 1	12/286 (4.20%)	8/282 (2.84%)
Ascites ^* 1	12/286 (4.20%)	17/282 (6.03%)
Constipation ^* 1	82/286 (28.67%)	61/282 (21.63%)
Diarrhoea ^* 1	59/286 (20.63%)	47/282 (16.67%)
Dry Mouth ^* 1	5/286 (1.75%)	10/282 (3.55%)
Dyspepsia ^* 1	23/286 (8.04%)	18/282 (6.38%)
Dysphagia ^* 1	1/286 (0.35%)	8/282 (2.84%)
Flatulence ^* 1	7/286 (2.45%)	8/282 (2.84%)
Gastrooesophageal Reflux Disease ^* 1	12/286 (4.20%)	15/282 (5.32%)
Mouth Ulceration ^* 1	6/286 (2.10%)	14/282 (4.96%)
Nausea ^* 1	212/286 (74.13%)	114/282 (40.43%)
Oral Pain ^* 1	5/286 (1.75%)	10/282 (3.55%)
Stomatitis ^* 1	52/286 (18.18%)	91/282 (32.27%)
Vomiting ^* 1	141/286 (49.30%)	54/282 (19.15%)
General disorders
Asthenia ^* 1	39/286 (13.64%)	16/282 (5.67%)
Chills ^* 1	8/286 (2.80%)	5/282 (1.77%)
Fatigue ^* 1	171/286 (59.79%)	113/282 (40.07%)
Malaise ^* 1	7/286 (2.45%)	5/282 (1.77%)
Mucosal Inflammation ^* 1	22/286 (7.69%)	33/282 (11.70%)
Non-Cardiac Chest Pain ^* 1	11/286 (3.85%)	8/282 (2.84%)
Oedema Peripheral ^* 1	32/286 (11.19%)	22/282 (7.80%)
Pain ^* 1	11/286 (3.85%)	5/282 (1.77%)
Peripheral Swelling ^* 1	9/286 (3.15%)	6/282 (2.13%)
Pyrexia ^* 1	38/286 (13.29%)	26/282 (9.22%)
Infections and infestations
Pneumonia ^* 1	5/286 (1.75%)	8/282 (2.84%)
Sinusitis ^* 1	5/286 (1.75%)	7/282 (2.48%)
Upper Respiratory Tract Infection ^* 1	14/286 (4.90%)	6/282 (2.13%)
Urinary Tract Infection ^* 1	12/286 (4.20%)	15/282 (5.32%)
Viral Upper Respiratory Tract Infection ^* 1	7/286 (2.45%)	11/282 (3.90%)
Injury, poisoning and procedural complications
Contusion ^* 1	8/286 (2.80%)	3/282 (1.06%)
Investigations
Alanine Aminotransferase Increased ^* 1	151/286 (52.80%)	12/282 (4.26%)
Aspartate Aminotransferase Increased ^* 1	100/286 (34.97%)	11/282 (3.90%)
Bilirubin Conjugated Increased ^* 1	24/286 (8.39%)	2/282 (0.71%)
Blood Alkaline Phosphatase Increased ^* 1	73/286 (25.52%)	16/282 (5.67%)
Blood Bilirubin Increased ^* 1	24/286 (8.39%)	3/282 (1.06%)
Blood Creatine Phosphokinase Increased ^* 1	13/286 (4.55%)	9/282 (3.19%)
Blood Creatinine Increased ^* 1	20/286 (6.99%)	21/282 (7.45%)
Blood Urea Increased ^* 1	6/286 (2.10%)	4/282 (1.42%)
Ejection Fraction Decreased ^* 1	20/286 (6.99%)	10/282 (3.55%)
Gamma-Glutamyltransferase Increased ^* 1	13/286 (4.55%)	5/282 (1.77%)
Haemoglobin Decreased ^* 1	6/286 (2.10%)	1/282 (0.35%)
Lymphocyte Count Decreased ^* 1	8/286 (2.80%)	4/282 (1.42%)
Neutrophil Count Decreased ^* 1	52/286 (18.18%)	37/282 (13.12%)
Platelet Count Decreased ^* 1	52/286 (18.18%)	16/282 (5.67%)
Weight Decreased ^* 1	13/286 (4.55%)	16/282 (5.67%)
White Blood Cell Count Decreased ^* 1	33/286 (11.54%)	29/282 (10.28%)
Metabolism and nutrition disorders
Decreased Appetite ^* 1	83/286 (29.02%)	52/282 (18.44%)
Dehydration ^* 1	21/286 (7.34%)	9/282 (3.19%)
Hyperglycaemia ^* 1	10/286 (3.50%)	6/282 (2.13%)
Hypoalbuminaemia ^* 1	21/286 (7.34%)	8/282 (2.84%)
Hypokalaemia ^* 1	22/286 (7.69%)	12/282 (4.26%)
Hypomagnesaemia ^* 1	19/286 (6.64%)	6/282 (2.13%)
Hyponatraemia ^* 1	14/286 (4.90%)	6/282 (2.13%)
Hypophosphataemia ^* 1	6/286 (2.10%)	2/282 (0.71%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	25/286 (8.74%)	12/282 (4.26%)
Back Pain ^* 1	24/286 (8.39%)	15/282 (5.32%)
Bone Pain ^* 1	11/286 (3.85%)	4/282 (1.42%)
Flank Pain ^* 1	8/286 (2.80%)	2/282 (0.71%)
Joint Swelling ^* 1	6/286 (2.10%)	2/282 (0.71%)
Muscular Weakness ^* 1	16/286 (5.59%)	9/282 (3.19%)
Musculoskeletal Chest Pain ^* 1	4/286 (1.40%)	7/282 (2.48%)
Myalgia ^* 1	16/286 (5.59%)	6/282 (2.13%)
Pain in Extremity ^* 1	8/286 (2.80%)	16/282 (5.67%)
Nervous system disorders
Dizziness ^* 1	7/286 (2.45%)	6/282 (2.13%)
Dizziness Postural ^* 1	10/286 (3.50%)	3/282 (1.06%)
Dysgeusia ^* 1	35/286 (12.24%)	20/282 (7.09%)
Headache ^* 1	38/286 (13.29%)	29/282 (10.28%)
Neuropathy Peripheral ^* 1	11/286 (3.85%)	13/282 (4.61%)
Peripheral Sensory Neuropathy ^* 1	7/286 (2.45%)	7/282 (2.48%)
Psychiatric disorders
Anxiety ^* 1	18/286 (6.29%)	8/282 (2.84%)
Depression ^* 1	8/286 (2.80%)	14/282 (4.96%)
Insomnia ^* 1	19/286 (6.64%)	16/282 (5.67%)
Renal and urinary disorders
Pollakiuria ^* 1	3/286 (1.05%)	7/282 (2.48%)
Reproductive system and breast disorders
Vulvovaginal Dryness ^* 1	1/286 (0.35%)	6/282 (2.13%)
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	41/286 (14.34%)	34/282 (12.06%)
Dyspnoea ^* 1	44/286 (15.38%)	28/282 (9.93%)
Dyspnoea Exertional ^* 1	10/286 (3.50%)	3/282 (1.06%)
Epistaxis ^* 1	12/286 (4.20%)	5/282 (1.77%)
Nasal Congestion ^* 1	10/286 (3.50%)	14/282 (4.96%)
Oropharyngeal Pain ^* 1	16/286 (5.59%)	17/282 (6.03%)
Productive Cough ^* 1	7/286 (2.45%)	5/282 (1.77%)
Respiratory Disorder ^* 1	6/286 (2.10%)	8/282 (2.84%)
Rhinitis Allergic ^* 1	6/286 (2.10%)	5/282 (1.77%)
Rhinorrhoea ^* 1	6/286 (2.10%)	4/282 (1.42%)
Skin and subcutaneous tissue disorders
Alopecia ^* 1	32/286 (11.19%)	22/282 (7.80%)
Dry Skin ^* 1	22/286 (7.69%)	21/282 (7.45%)
Erythema ^* 1	3/286 (1.05%)	7/282 (2.48%)
Night Sweats ^* 1	5/286 (1.75%)	6/282 (2.13%)
Palmar-Plantar Erythrodysaesthesia Syndrome ^* 1	58/286 (20.28%)	117/282 (41.49%)
Pigmentation Disorder ^* 1	5/286 (1.75%)	6/282 (2.13%)
Pruritus ^* 1	11/286 (3.85%)	14/282 (4.96%)
Rash ^* 1	22/286 (7.69%)	26/282 (9.22%)
Rash Maculo-Papular ^* 1	8/286 (2.80%)	24/282 (8.51%)
Skin Hyperpigmentation ^* 1	10/286 (3.50%)	12/282 (4.26%)
Skin Toxicity ^* 1	3/286 (1.05%)	6/282 (2.13%)
Skin Ulcer ^* 1	0/286 (0.00%)	6/282 (2.13%)
Vascular disorders
Hot Flush ^* 1	7/286 (2.45%)	8/282 (2.84%)
Hypertension ^* 1	22/286 (7.69%)	7/282 (2.48%)
Hypotension ^* 1	11/286 (3.85%)	4/282 (1.42%)
1 Term from vocabulary, MedDRA Version 19.0 * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

If an investigator wishes to publish information from 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 by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.

Results Point of Contact

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Name/Title:	Senior Medical Director
Organization:	Janssen Research & Development, LLC
Phone:	844-434-4210
EMail:	ClinicalTrialDisclosure@its.jnj.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jones RL, Herzog TJ, Patel SR, von Mehren M, Schuetze SM, Van Tine BA, Coleman RL, Knoblauch R, Triantos S, Hu P, Shalaby W, McGowan T, Monk BJ, Demetri GD. Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer. Cancer Med. 2021 Jun;10(11):3565-3574. doi: 10.1002/cam4.3903. Epub 2021 May 7.

Monk BJ, Herzog TJ, Wang G, Triantos S, Maul S, Knoblauch R, McGowan T, Shalaby WSW, Coleman RL. A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer. Gynecol Oncol. 2020 Mar;156(3):535-544. doi: 10.1016/j.ygyno.2019.12.043. Epub 2020 Jan 8.

Layout table for additonal information

Responsible Party:	Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:	NCT01846611
Other Study ID Numbers:	CR100983 ET743OVC3006 ( Other Identifier: Janssen Research & Development, LLC ) 2012-004808-34 ( EudraCT Number )
First Submitted:	May 1, 2013
First Posted:	May 3, 2013
Results First Submitted:	January 17, 2019
Results First Posted:	February 6, 2019
Last Update Posted:	April 1, 2019

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