Safety and Efficacy Study of Trabectedin for the Treatment of Localized Myxoid / Round Cell Liposarcoma

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00579501
• Collaborator: PharmaMar (Industry)
• Enrollment: 29
• Locations: 8
• Arm: 1
• Duration (Months): 33.1
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of trabectedin for the treatment of localized (non-metastatic) myxoid / round cell liposarcoma (malignant tumor derived from primitive or embryonal lipoblastic cells).

Condition or Disease	Intervention/Treatment	Phase
Liposarcoma,Myxoid	Drug: Trabectedin; Drug: Dexamethasone	Phase 2

Detailed Description

This is an open-label (all people know the identity of the intervention), prospective (study following participants forward in time), multicenter (when more than one hospital or medical school team work on a medical research study) study of trabectedin for the treatment of localized myxoid / round cell liposarcoma (MRCL). Trabectedin will be given at 1.5 milligram per meter square (mg/m^2) over a 24-hour intravenous (iv) infusion every 3 weeks for a minimum of 3 and a maximum of 6 cycles along with dexamethasone 20 mg iv which will be given within 30 minutes before start of each trabectedin iv infusion. Participants whose myxoid/round cell liposarcoma (MRCL) do not progress at the end of the neoadjuvant treatment will be followed every 6 weeks for disease progression or until 6 months post definitive surgery, in the absence of unacceptable toxicity and/or disease progression. Efficacy will be assessed by determining the pathologic Complete Response (pCR) rate assessed in the tumor surgical specimen by a central pathology review. Participants' safety will be monitored throughout the trial.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Phase II Clinical Trial of Neoadjuvant Trabectedin (Yondelis) in Patients With Localized Myxoid / Round Cell Liposarcoma
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Trabectedin Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) will be given as an intravenous (iv) infusion (a fluid or a medicine delivered into a vein by way of a needle) over 24-hour every 3 weeks for a minimum of 3 and a maximum of 6 cycles prior to definitive surgery. Dexamethasone 20 mg iv will also be administered within 30 minutes before start of each trabectedin infusion.

Drug: Trabectedin; Trabectedin 1.5 mg/m^2 over a 24-hour iv infusion every 3 weeks for a minimum of 3 and a maximum of 6 cycles of trabectedin.; Drug: Dexamethasone; Dexamethasone 20 mg iv will be administered within 30 minutes before start of each trabectedin iv infusion

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Pathological Complete Response (pCR) [Every 6 weeks until disease progression (up to Week 33) or 6 months post surgery.]

   Complete pathological response is complete disappearance of the tumor tissue up to the molecular level.

Secondary Outcome Measures

1. Percentage of Participants With Objective Tumor Response Based on Response Evaluation Criteria In Solid Tumors (RECIST) [Every 6 weeks until disease progression (up to Week 33) or 6 months post surgery.]

   The objective tumor response is defined as the percentage of participants achieving partial response (PR) on tumor response assessed by RECIST. The PR is at least 30 percent decrease in sum of the longest diameter of target lesions or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pathological diagnosis of myxoid / round cell liposarcoma (MRCL) and availability of pathology specimens for central review and pharmacogenomic studies

• Clinical evidence of locally advanced (Stage III), non-metastatic tumor, including locally recurring disease after initial surgery

• Measurable disease (by Response Evaluation Criteria In Solid Tumors [RECIST])

• No prior chemotherapy or radiation (except for adjuvant post-operative radiotherapy)

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2

Exclusion Criteria:

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

• Pregnant or lactating women and women of reproductive potential who are not using effective contraceptive methods

• History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 5 years or longer

• Known distant metastases

• Other serious illnesses such as congestive heart failure or angina pectoris, myocardial infarction within 1 year before enrollment, uncontrolled arterial hypertension or arrhythmias

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Coeur D Alene	Idaho	United States
2		Park Ridge	Illinois	United States
3		Iowa City	Iowa	United States
4		Boston	Massachusetts	United States
5		Bourdeaux		France
6		Lyon		France
7		Villejuif		France
8		Mannheim		Germany

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

Publications

None provided.

• Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT00579501
• Other Study ID Numbers: CR014767; ET-B-028-06
• First Posted: Dec 24, 2007
• Last Update Posted: May 7, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: Myxoid; Liposarcoma; Trabectedin; Dexamethasone
• Additional relevant MeSH terms: Liposarcoma; Liposarcoma, Myxoid; Dexamethasone; Trabectedin

Study Results

Participant Flow

Arm/Group Title	Trabectedin
Arm/Group Description	Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (iv) infusion (a fluid or a medicine delivered into a vein by way of a needle) over 24-hour every 3 weeks for a minimum of 3 and a maximum of 6 cycles prior to definitive surgery. Dexamethasone 20 mg iv was also administered within 30 minutes before start of each trabectedin infusion.
Period Title: Overall Study
STARTED	29
COMPLETED	0
NOT COMPLETED	29

Baseline Characteristics

Arm/Group Title	Trabectedin
Arm/Group Description	Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (iv) infusion (a fluid or a medicine delivered into a vein by way of a needle) over 24-hour every 3 weeks for a minimum of 3 and a maximum of 6 cycles prior to definitive surgery. Dexamethasone 20 mg iv was also administered within 30 minutes before start of each trabectedin infusion.
Overall Participants	29
Age, Customized (participants) [Number]
18-49 years	15 51.7%
50-69 years	10 34.5%
greater than or equal to 70 years	4 13.8%
Sex: Female, Male (Count of Participants)
Female	13 44.8%
Male	16 55.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Pathological Complete Response (pCR)
Description	Complete pathological response is complete disappearance of the tumor tissue up to the molecular level.
Time Frame	Every 6 weeks until disease progression (up to Week 33) or 6 months post surgery.

Outcome Measure Data

Analysis Population Description

Participants who received at least one cycle of trabectedin and have adequate pre and post trabectedin pathologic specimens available. Six participants were non evaluable for pCR assessment.

Arm/Group Title	Trabectedin
Arm/Group Description	Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (iv) infusion (a fluid or a medicine delivered into a vein by way of a needle) over 24-hour every 3 weeks for a minimum of 3 and a maximum of 6 cycles prior to definitive surgery. Dexamethasone 20 mg iv was also administered within 30 minutes before start of each trabectedin infusion.
Measure Participants	23
Number [percentage of participants]	13 44.8%

2. Secondary Outcome

Title	Percentage of Participants With Objective Tumor Response Based on Response Evaluation Criteria In Solid Tumors (RECIST)
Description	The objective tumor response is defined as the percentage of participants achieving partial response (PR) on tumor response assessed by RECIST. The PR is at least 30 percent decrease in sum of the longest diameter 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	Every 6 weeks until disease progression (up to Week 33) or 6 months post surgery.

Outcome Measure Data

Analysis Population Description

Participants who received at least one cycle of trabectedin and have at least one post baseline disease assessment.

Arm/Group Title	Trabectedin
Arm/Group Description	Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (iv) infusion (a fluid or a medicine delivered into a vein by way of a needle) over 24-hour every 3 weeks for a minimum of 3 and a maximum of 6 cycles prior to definitive surgery. Dexamethasone 20 mg iv was also administered within 30 minutes before start of each trabectedin infusion.
Measure Participants	29
Number [percentage of participants]	24.1 83.1%

Adverse Events

Arm/Group Title	Trabectedin
Arm/Group Description	Trabectedin at a dose of 1.5 milligram per meter square (mg/m^2) was given as an intravenous (iv) infusion (a fluid or a medicine delivered into a vein by way of a needle) over 24-hour every 3 weeks for a minimum of 3 and a maximum of 6 cycles prior to definitive surgery. Dexamethasone 20 mg iv was also administered within 30 minutes before start of each trabectedin infusion.
All Cause Mortality
	Trabectedin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Trabectedin
	Affected / at Risk (%)	# Events
Total	6/29 (20.7%)
Gastrointestinal disorders
Colitis ischaemic	1/29 (3.4%)
Constipation	1/29 (3.4%)
Nausea	1/29 (3.4%)
Stomatitis	1/29 (3.4%)
General disorders
Asthenia	1/29 (3.4%)
Hepatobiliary disorders
Hepatic failure	1/29 (3.4%)
Investigations
Alanine aminotransferase increased	1/29 (3.4%)
Aspartate aminotransferase increased	1/29 (3.4%)
Liver function test abnormal	1/29 (3.4%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/29 (3.4%)
Renal and urinary disorders
Renal failure	1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	Trabectedin
	Affected / at Risk (%)	# Events
Total	28/29 (96.6%)
Blood and lymphatic system disorders
Anaemia	2/29 (6.9%)
Leukopenia	1/29 (3.4%)
Neutropenia	14/29 (48.3%)
Cardiac disorders
Bradycardia	1/29 (3.4%)
Palpitations	1/29 (3.4%)
Tachycardia	2/29 (6.9%)
Ventricular extrasystoles	1/29 (3.4%)
Gastrointestinal disorders
Abdominal pain	4/29 (13.8%)
Abdominal pain upper	1/29 (3.4%)
Constipation	7/29 (24.1%)
Diarrhoea	3/29 (10.3%)
Gastritis	1/29 (3.4%)
Gastrooesophageal reflux disease	1/29 (3.4%)
Nausea	22/29 (75.9%)
Reflux gastritis	1/29 (3.4%)
Stomach discomfort	1/29 (3.4%)
Vomiting	8/29 (27.6%)
General disorders
Chest pain	1/29 (3.4%)
Chills	1/29 (3.4%)
Fatigue	19/29 (65.5%)
Infusion site pain	2/29 (6.9%)
Mucosal inflammation	1/29 (3.4%)
Oedema	3/29 (10.3%)
Oedema peripheral	3/29 (10.3%)
Pyrexia	8/29 (27.6%)
Hepatobiliary disorders
Hepatotoxicity	1/29 (3.4%)
Immune system disorders
Hypersensitivity	1/29 (3.4%)
Infections and infestations
Bronchitis	1/29 (3.4%)
Gastroenteritis	1/29 (3.4%)
Herpes zoster	1/29 (3.4%)
Influenza	1/29 (3.4%)
Injection site infection	1/29 (3.4%)
Tooth infection	1/29 (3.4%)
Injury, poisoning and procedural complications
Thrombosis in device	1/29 (3.4%)
Investigations
Alanine aminotransferase increased	6/29 (20.7%)
Blood bilirubin increased	2/29 (6.9%)
Blood creatine phosphokinase increased	1/29 (3.4%)
Gamma-glutamyltransferase increased	1/29 (3.4%)
Weight decreased	2/29 (6.9%)
Weight increased	2/29 (6.9%)
Metabolism and nutrition disorders
Anorexia	3/29 (10.3%)
Decreased appetite	1/29 (3.4%)
Hypoalbuminaemia	1/29 (3.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/29 (3.4%)
Back pain	3/29 (10.3%)
Muscular weakness	1/29 (3.4%)
Myalgia	1/29 (3.4%)
Pain in extremity	1/29 (3.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	6/29 (20.7%)
Nervous system disorders
Paraesthesia	1/29 (3.4%)
Headache	5/29 (17.2%)
Psychiatric disorders
Anxiety	2/29 (6.9%)
Depression	1/29 (3.4%)
Insomnia	3/29 (10.3%)
Renal and urinary disorders
Pollakiuria	1/29 (3.4%)
Respiratory, thoracic and mediastinal disorders
Cough	1/29 (3.4%)
Dysphonia	1/29 (3.4%)
Dyspnoea	1/29 (3.4%)
Lung infiltration	3/29 (10.3%)
Nasal congestion	1/29 (3.4%)
Skin and subcutaneous tissue disorders
Erythema	1/29 (3.4%)
Hyperhidrosis	1/29 (3.4%)
Vascular disorders
Hypertension	1/29 (3.4%)
Phlebitis	2/29 (6.9%)
Thrombophlebitis superficial	1/29 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Before submitting the paper or abstract or disclose information to public concerning trabectedin (YONDELIS®), PharmaMar must be provided of 15 days in case of abstract and 30 days in case of full paper, to review and approve the publication to assure that confidential and proprietary data are protected. Primary authorship for publication is hold by the coordinating investigator of this project. Following authors will be named according to the number of patients treated under this protocol.