Trabectedin in Treating Young Patients With Recurrent or Refractory Soft Tissue Sarcoma or Ewing's Family of Tumors

NCT ID: NCT00070109

Last Updated: 2018-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2013-12-31

Brief Summary

This phase II trial is studying how well trabectedin works in treating young patients with recurrent or refractory soft tissue sarcoma or Ewing's family of tumors. Drugs used in chemotherapy such as trabectedin use different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the response rate in pediatric patients with recurrent or refractory soft tissue sarcomas or Ewing's sarcoma family of tumors treated with ecteinascidin 743 (trabectedin).

II. Determine the toxicity of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients.

OUTLINE:

Patients receive trabectedin IV over 3 hours on day 1. Treatment repeats every 21days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 5 years.

Conditions

Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma; Peripheral Primitive Neuroectodermal Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trabectedin 1.3 mg/m2 to assess feasibility in all patients

Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. A cohort of 6 patients will be enrolled at the 1.3 mg/m2 dose level.

Group Type: EXPERIMENTAL

trabectedin

Intervention Type: DRUG

Given IV

pharmacological study

Intervention Type: OTHER

Correlative studies

Trabectedin 1.5 mg/m2 to assess feasibility in all patients

Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. Six toxicity-evaluable patients are assigned this treatment.

Group Type: EXPERIMENTAL

trabectedin

Intervention Type: DRUG

Given IV

pharmacological study

Intervention Type: OTHER

Correlative studies

Trabectedin at 1.5 mg/m2 to assess efficacy in Ewing sarcoma

Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

trabectedin

Intervention Type: DRUG

Given IV

pharmacological study

Intervention Type: OTHER

Correlative studies

Trabectedin at 1.5 mg/m2 - assess efficacy in rhabdomyosarcoma

Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

trabectedin

Intervention Type: DRUG

Given IV

pharmacological study

Intervention Type: OTHER

Correlative studies

Trabectedin 1.5 mg/m2 - assess efficacy in nonrhabdomyosarcoma

Patients receive trabectedin over 3 hours on day 1. Treatment repeats every 21 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

trabectedin

Intervention Type: DRUG

Given IV

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

trabectedin

Given IV

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Ecteinascidin; ET 743; Yondelis; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• Patients must be greater than or equal to 12 months of age at the time of study entry and no more than 21 years of age when initially diagnosed with the malignancy to be treated on this protocol
• Histologically confirmed recurrent or refractory sarcoma tumors, including the following:

• Rhabdomyosarcoma
• Nonrhabdomyosarcomatous soft tissue sarcoma
• Ewing's sarcoma
• Measurable disease by imaging studies

• Lesions assessable only by radionuclide scans are not considered measurable
• If the only measurable lesion has been previously irradiated, then that lesion must have shown evidence of an interim increase in size
• No significant amount of metastatic liver disease, defined as the following:

• Lesions occupying more than 25% of the liver by imaging and abnormal liver function tests or abnormal synthetic liver function
• Performance status - Lansky 50-100% (10 years of age and under)
• Performance status - Karnofsky 50-100% (over 10 years of age)
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3 (transfusion independent)
• Hemoglobin at least 8.0 g/dL (transfusion allowed)
• No concurrent CYP3A4 inhibitors, including the following:

• Grapefruit juice
• Erythromycin
• Azithromycin
• Clarithromycin
• Rifampin and its analogs
• Fluconazole
• Ketoconazole
• Itraconazole
• Cimetidine
• Cannabinoids (marijuana or dronabinol)
• Leukotriene inhibitors used in asthma (e.g., zafirlukast, montelukast, or zileuton)
• Bilirubin no greater than upper limit of normal (ULN)
• Total alkaline phosphatase no greater than ULN
• Hepatic fraction alkaline phosphatase and 5 nucleotidase no greater than ULN
• SGOT and SGPT ≤ 2.5 times ULN
• Albumin ≥ 2.5 g/dL
• Gamma-glutamyl transferase < 2.5 times ULN
• Maximum creatinine based on age as follows:

• 0.8 mg/dL (5 years of age and under)
• 1.0 mg/dL (6 to 10 years of age)
• 1.2 mg/dL (11 to 15 years of age)
• 1.5 mg/dL (over 15 years of age)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) at least 70 mL/min
• No uncompensated congestive heart failure within the past 6 months
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 2 months after study participation
• No active uncontrolled infection
• Weight ≥ 15 kilograms
• More than 1 week since prior growth factors that support platelet or white blood cell number or function
• At least 7 days since prior biologic agents and recovered
• No prior allogeneic stem cell transplantation
• No other concurrent immunomodulating agents
• More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
• No more than 2 prior multi-agent chemotherapy regimens
• No other concurrent anticancer chemotherapy
• Concurrent steroids allowed
• At least 6 weeks since prior since prior extended radiotherapy and recovered
• No prior total body radiotherapy
• Concurrent radiotherapy to localized painful lesions allowed provided at least 1 measurable lesion is not irradiated*
• At least 7 days since prior enzyme-inducing anticonvulsants (e.g., carbamazepine, phenobarbital, or phenytoin)
• No concurrent enzyme-inducing anticonvulsants
• No other concurrent investigational agents

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sylvain Baruchel, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Children's Hospital Central California

Madera, California, United States

Childrens Memorial Hospital

Chicago, Illinois, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

New York University Langone Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

University of Vermont

Burlington, Vermont, United States

Seattle Children's Hospital

Seattle, Washington, United States

Chedoke-McMaster Hospitals

Hamilton, Ontario, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

Hospital Sainte-Justine

Montreal, Quebec, Canada

Countries

United States; Canada

References

Baruchel S, Pappo A, Krailo M, Baker KS, Wu B, Villaluna D, Lee-Scott M, Adamson PC, Blaney SM. A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: a report from the Children's Oncology Group. Eur J Cancer. 2012 Mar;48(4):579-85. doi: 10.1016/j.ejca.2011.09.027. Epub 2011 Nov 14.

Reference Type: RESULT

PMID: 22088484 (View on PubMed)

Other Identifiers

NCI-2009-00357

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000329999

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ADVL0221

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ADVL0221

Identifier Type: -

Identifier Source: org_study_id