A Study of Trabectedin or Dacarbazine for the Treatment of Patients With Advanced Liposarcoma or Leiomyosarcoma

NCT01343277 | Completed Phase 3 Results DMC

• 2 other identifiers: CR018004ET743SAR3007
• Study Type: interventional
• Target: 579
• Locations: 4 countries
• Sites: 88

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).

Conditions

Advanced Liposarcoma or Leiomyosarcoma

Keywords

Advanced Liposarcoma or Leiomyosarcoma; Trabectedin; Yondelis; Dacarbazine; Anthracycline; L-sarcoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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.

  approximately 3 years 8 months (From Study start date [27 May 2011] up to final analysis data cut-off [05 January 2015]

Secondary Outcomes (5)

• 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])

• 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])

• 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])

• 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])

• 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])

Study Arms (2)

Trabectedin

EXPERIMENTAL

Drug: Trabectedin

Dacarbazine

ACTIVE COMPARATOR

Drug: Dacarbazine

Interventions

Trabectedin DRUG

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.

Trabectedin

Dacarbazine DRUG

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.

Dacarbazine

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead
• PharmaMar: collaborator

Study Sites (88)

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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Santa Monica, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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Hartford, Connecticut, United States

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New Haven, Connecticut, United States

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Boynton Beach, Florida, United States

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Hollywood, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Savannah, Georgia, United States

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Post Falls, Idaho, United States

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Chicago, Illinois, United States

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Naperville, Illinois, United States

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Park Ridge, Illinois, United States

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Peoria, Illinois, United States

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Springfield, Illinois, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Sioux City, Iowa, United States

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Overland Park, Kansas, United States

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Wichita, Kansas, United States

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Louisville, Kentucky, United States

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Covington, Louisiana, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Lansing, Michigan, United States

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Jackson, Mississippi, United States

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Saint Joseph, Missouri, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Henderson, Nevada, United States

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Las Vegas, Nevada, United States

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Lebanon, New Hampshire, United States

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Hackensack, New Jersey, United States

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Morristown, New Jersey, United States

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Newark, New Jersey, United States

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Albuquerque, New Mexico, United States

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Johnson City, New York, United States

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New York, New York, United States

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Syracuse, New York, United States

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The Bronx, New York, United States

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Chapel Hill, North Carolina, United States

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Charlotte, North Carolina, United States

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Akron, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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State College, Pennsylvania, United States

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Charleston, South Carolina, United States

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Knoxville, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Fairfax, Virginia, United States

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Seattle, Washington, United States

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Morgantown, West Virginia, United States

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Green Bay, Wisconsin, United States

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Milwaukee, Wisconsin, United States

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Malvern, Australia

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Randwick, Australia

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Subiaco, Australia

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Woolloongabba, Australia

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Bahia, Brazil

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Barretos, Brazil

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Ijuí, Brazil

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Porto Alegre, Brazil

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São Paulo, Brazil

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Auckland, New Zealand

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Wellington, New Zealand

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Related Publications (5)

• 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.

  PMID: 33960681 DERIVED

• Patel S, von Mehren M, Reed DR, Kaiser P, Charlson J, Ryan CW, Rushing D, Livingston M, Singh A, Seth R, Forscher C, D'Amato G, Chawla SP, McCarthy S, Wang G, Parekh T, Knoblauch R, Hensley ML, Maki RG, Demetri GD. Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Cancer. 2019 Aug 1;125(15):2610-2620. doi: 10.1002/cncr.32117. Epub 2019 Jun 7.

  PMID: 31173362 DERIVED

• Jones RL, Demetri GD, Schuetze SM, Milhem M, Elias A, Van Tine BA, Hamm J, McCarthy S, Wang G, Parekh T, Knoblauch R, Hensley ML, Maki RG, Patel S, von Mehren M. Efficacy and tolerability of trabectedin in elderly patients with sarcoma: subgroup analysis from a phase III, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Ann Oncol. 2018 Sep 1;29(9):1995-2002. doi: 10.1093/annonc/mdy253.

  PMID: 30084934 DERIVED

• Calvo E, Azaro A, Rodon J, Dirix L, Huizing M, Senecal FM, LoRusso P, Yee L, Poggesi I, de Jong J, Triantos S, Park YC, Knoblauch RE, Parekh TV, Demetri GD, von Mehren M. Hepatic safety analysis of trabectedin: results of a pharmacokinetic study with trabectedin in patients with hepatic impairment and experience from a phase 3 clinical trial. Invest New Drugs. 2018 Jun;36(3):476-486. doi: 10.1007/s10637-017-0546-9. Epub 2017 Nov 27.

  PMID: 29177975 DERIVED

• Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. doi: 10.1200/JCO.2015.62.4734. Epub 2015 Sep 14.

  PMID: 26371143 DERIVED

MeSH Terms

Conditions

Leiomyosarcoma

Interventions

Trabectedin; Dacarbazine

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Triazenes; Organic Chemicals; Imidazoles; Azoles

Results Point of Contact

• Title: Senior Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2011
• First Posted: April 28, 2011
• Study Start: June 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: April 1, 2016
• Last Updated: August 26, 2016
• Results First Posted: January 28, 2016

Record last verified: 2016-07

Locations

AU (4); US (77); BR (5); NZ (2)