Clinical trial NCT00070109: Trabectedin in Treating Young Patients With Recurrent or Refractory Soft Tissue Sarcoma or Ewing's Family of Tumors
Official title: A Phase II Study Of Trabectedin (ET-743, Yondelis®) in Children With Recurrent Rhabdomyosarcoma, Ewing Sarcoma, or Nonrhabdomyosarcomatous Soft Tissue Sarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Previously Treated Childhood Rhabdomyosarcoma
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Soft Tissue Sarcoma
Recurrent Ewing Sarcoma
Peripheral Primitive Neuroectodermal Tumor
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-10-07
Enrollment: 50
Sex: ALL
Minimum age (years): 12
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Response (Complete Response [CR] and Partial Response [PR])
timeFrame: Twenty-six (26) cycles of chemotherapy or termination of protocol therapy, whichever occurs first.
measure: Number of Patients With Dose-Limiting Toxicity (DLT)
timeFrame: 1 Cycle
measure: Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Maximum Plasma Concentration (Cmax) of Trabectedin
timeFrame: From baseline up to168 hours after trabectedin infusion in course 1
measure: Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Apparent Volume at Steady State (Vss) of Trabectedin
timeFrame: From baseline up to168 hours after trabectedin infusion in course 1
measure: Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Half-life of Trabectedin
timeFrame: From baseline up to168 hours after trabectedin infusion in course 1
measure: Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Area Under the Curve (AUC) of Trabectedin
timeFrame: From baseline up to168 hours after trabectedin infusion in course 1
measure: Pharmacokinetics by a Miniaturized Liquid Chromatography/Tandem Mass Spectrometry Method : Clearance of Trabectedin
timeFrame: From baseline up to168 hours after trabectedin infusion in course 1
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Chicago
country: United States
facility: Childrens Memorial Hospital
state: Illinois
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Hamilton
country: Canada
facility: Chedoke-McMaster Hospitals
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Hospital Sainte-Justine
state: Quebec
Study officials:
affiliation: Children's Oncology Group
name: Sylvain Baruchel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.