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

NCT ID: NCT01343277

Last Updated: 2016-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 579 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2016-04-30

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).

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/m^2) 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/m^2 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.

Conditions

Advanced Liposarcoma or Leiomyosarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trabectedin

Group Type: EXPERIMENTAL

Trabectedin

Intervention Type: 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.

Dacarbazine

Group Type: ACTIVE_COMPARATOR

Dacarbazine

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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:

• 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

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

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Phoenix, Arizona, United States

Tucson, Arizona, United States

Little Rock, Arkansas, United States

La Jolla, California, United States

Los Angeles, California, United States

San Diego, California, United States

San Francisco, California, United States

Santa Monica, California, United States

Aurora, Colorado, United States

Denver, Colorado, United States

Hartford, Connecticut, United States

New Haven, Connecticut, United States

Boynton Beach, Florida, United States

Hollywood, Florida, United States

Miami, Florida, United States

Orlando, Florida, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Augusta, Georgia, United States

Savannah, Georgia, United States

Post Falls, Idaho, United States

Chicago, Illinois, United States

Naperville, Illinois, United States

Park Ridge, Illinois, United States

Peoria, Illinois, United States

Springfield, Illinois, United States

Indianapolis, Indiana, United States

Iowa City, Iowa, United States

Sioux City, Iowa, United States

Overland Park, Kansas, United States

Wichita, Kansas, United States

Louisville, Kentucky, United States

Covington, Louisiana, United States

Baltimore, Maryland, United States

Boston, Massachusetts, United States

Ann Arbor, Michigan, United States

Detroit, Michigan, United States

Lansing, Michigan, United States

Jackson, Mississippi, United States

Saint Joseph, Missouri, United States

St Louis, Missouri, United States

Omaha, Nebraska, United States

Henderson, Nevada, United States

Las Vegas, Nevada, United States

Lebanon, New Hampshire, United States

Hackensack, New Jersey, United States

Morristown, New Jersey, United States

Newark, New Jersey, United States

Albuquerque, New Mexico, United States

Johnson City, New York, United States

New York, New York, United States

Syracuse, New York, United States

The Bronx, New York, United States

Chapel Hill, North Carolina, United States

Charlotte, North Carolina, United States

Akron, Ohio, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States

Oklahoma City, Oklahoma, United States

Tulsa, Oklahoma, United States

Portland, Oregon, United States

Philadelphia, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

State College, Pennsylvania, United States

Charleston, South Carolina, United States

Knoxville, Tennessee, United States

Nashville, Tennessee, United States

Austin, Texas, United States

Dallas, Texas, United States

Houston, Texas, United States

San Antonio, Texas, United States

Salt Lake City, Utah, United States

Fairfax, Virginia, United States

Seattle, Washington, United States

Morgantown, West Virginia, United States

Green Bay, Wisconsin, United States

Milwaukee, Wisconsin, United States

Malvern, , Australia

Randwick, , Australia

Subiaco, , Australia

Woolloongabba, , Australia

Bahia, , Brazil

Barretos, , Brazil

Ijuí, , Brazil

Porto Alegre, , Brazil

São Paulo, , Brazil

Auckland, , New Zealand

Wellington, , New Zealand

Countries

United States; Australia; Brazil; New Zealand

References

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.

Reference Type: DERIVED

PMID: 33960681 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31173362 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30084934 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29177975 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26371143 (View on PubMed)

Other Identifiers

ET743SAR3007

Identifier Type: OTHER

Identifier Source: secondary_id

CR018004

Identifier Type: -

Identifier Source: org_study_id