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Tabectedin to Treat Children and Adolescents With Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01453283
Recruitment Status : Completed
First Posted : October 17, 2011
Last Update Posted : July 2, 2017
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

Background:

  • Trabectedin is an experimental drug that kills some cancer cells in the laboratory and in mice by interfering with genetic material (DNA) in cancer cells.
  • In some adult patients with cancer who received trabectedin, tumors grew slower or shrank.

Objectives:

  • To determine a dose of trabectedin that can be given safely to children and adolescents as a 24-hour continuous infusion through a vein.
  • To determine the side effects of trabectedin in children and adolescents.
  • To study how the body handles trabectedin by measuring the amount of the drug in the bloodstream over time after a dose is given.
  • To measure the effect of trabectedin on DNA in white blood cells.
  • To determine if an individual's tumor cells have a specific proteins involved in DNA repair and if a pattern of genes can be identified in tumor samples that might help explain why trabectedin reduces tumors in some individuals and not others.
  • To study genetic factors that may influence the way the body handles trabectedin.
  • To see if trabectedin is beneficial in certain types of cancer.

Eligibility:

-Children between 4 year and 17 years of age with tumors that recur or no longer respond to standard treatment.

Design:

  • Patients receive trabectedin as a 24-hour continuous infusion repeated every 21 days. The first three children entering the study receive a dose of 1.1 mg/m2. Subsequent groups of up to six patients receive higher doses (1.5 mg/m2 and 1.7 mg/m2) as long as the preceding dose is well tolerated. Patients enrolled at the lowest dose level may have their dose increased to the next level if they tolerated the lower dose well. Treatment may continue as long as the cancer does not worsen and the treatment is tolerated.
  • Patients have blood drawn on days 1, 2, 3, 4, 5 and 7 of the first treatment cycle to study how the body handles trabectedin.
  • A tumor sample obtained from a prior surgery or biopsy is examined for proteins involved in DNA repair.
  • A blood sample is drawn to look for genetic factors that may influence how the body handles trabectedin.
  • Patients have periodic physical examinations and blood tests. MRI or CT scans are done before starting therapy and after every two treatment cycles to evaluate the tumor.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Trabectedin (ecteinascidin-743, ET-743, YONDELIS [R]) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Primary Purpose: Treatment
Official Title: A Phase I Trial and Pharmacokinetic Study of Trabectedin (YONDELIS [R], ET-743) in Children and Adolescents With Relapsed or Refractory Solid Tumors
Study Start Date : December 20, 2006
Actual Primary Completion Date : October 11, 2011
Actual Study Completion Date : October 11, 2011






Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

AGE: greater than or equal to 4 years and less than 17 years of age.

DIAGNOSIS: Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, germ cell tumors, and brain tumors with the exception that histologic confirmation is not required for patients with optic or brainstem gliomas.

MEASURABLE/EVALUABLE DISEASE: Patients must have measurable or evaluable disease.

PRIOR THERAPY: The patient's cancer must have relapsed after or failed to respond to frontline curative therapy and there must not be other potentially curative treatment options available.

  • Patients must have fully recovered to less than or equal to grade 1 from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  • Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks prior to study entry.
  • Growth factors: The last dose of growth factors such as filgrastim and epoetin must be at least one week prior to study entry, the last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be 2 weeks prior to study entry.
  • Investigational anti-cancer agents: The last dose of all investigational agents must be at least 30 days prior to study entry.
  • Biologic anti-cancer agents: The last dose of non-myelosuppressive biologic agents for the treatment of the patient's cancer (example, retinoids) must be at least 7 days prior to study entry.
  • Radiation therapy: The last dose of radiation to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study entry, TBI and craniospinal radiation must be completed at least 4 months prior to study entry. The last dose of all other local palliative radiation must be at least 2 weeks prior to study entry.
  • Stem Cell Transplantation. Patients must be at least 2 months post-autologous transplant and recovered from treatment-related toxicities. Patients who have received an allogeneic transplant are excluded.

CONCOMITANT MEDICATIONS:

-Patients with brain tumors must be on a stable or tapering dose of corticosteroids for 7 days prior to the date of the baseline scan performed for the purpose of assessing response to therapy on this study.

PERFORMANCE STATUS: Patients must have a Lansky (less than or equal to 10 years old) or Karnofsky (greater than 10 years old) score of greater than or equal to 60%.

HEMATOLOGIC FUNCTION: Peripheral absolute neutrophil count greater than or equal to 1,500/microliter and a platelet count greater than or equal to 75,000/microliter independent of transfusion, and a hemoglobin of greater than or equal to 8 gm/dl (transfusion permitted to achieve this level).

HEPATIC FUNCTION:

  • ALT (SGPT) and AST (SGOT) must be less than or equal to 2.5 x the upper limit of normal (ULN).
  • Bilirubin must be less than or equal to ULN. If the patient has Gilbert's syndrome, normal bilirubin is not required but should be discussed with the PI or study chair.
  • Alkaline phosphatase must be less than or equal to ULN for age and sex or if alkaline phosphatase greater than ULN then 5' nucleotidase must be less than or equal to ULN or the gamma-glutamyl transpeptidase (GGT) must be less than or equal to 2.5 times the ULN to be eligible.

Normal Values for Alkaline Phosphatase at the NIH Clinical Center (U/L):

Age between 4 to 6 years with a normal value (U/L) in Males 93 to 309 and a normal value (U/L) in Females 96 to 297.

Age between 7 to 9 years with a normal value (U/L) in Males 86 to 315 and a normal value (U/L) in Females 69 to 325.

Age between 10 to 12 years with a normal value (U/L) in Males 42 to 362 and a normal value (U/L) in Females 51 to 332.

Age between 13 to 15 years with a normal value (U/L) in Males 74 to 390 and a normal value (U/L) in Females 50 to 162.

Age between 16 to 18 years with a normal value (U/L) in Males 52 to 171 and a normal value (U/L) in Females 47 to 119.

OTHER: creatine kinase less than or equal to 2.5 times the ULN.

RENAL FUNCTION: Age-adjusted serum creatinine OR a creatinine clearance greater than or equal to 60 mL/min/1.73 m(2).

Age less than or equal to 5 with a serum creatinine less than or equal to 0.8 (mg/dl).

Age greater than 5 years and less than or equal to 10 with a serum creatinine of less than or equal to 1.0 (mg/dl).

Age greater than 10 and less than or equal to 15 with a serum creatinine less than or equal to 1.2 (mg/dl).

Age greater than 15 with a serum creatinine less than or equal to 1.5 (mg/dl).

EXCLUSION CRITERIA:

Patients with severe uncontrolled infections or other unrelated systemic illnesses, which in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate trabectedin or are likely to interfere with the study procedures or results.

Patients with known history of xeroderma pigmentosum or other diseases with reduced DNA repair.

Pregnant or breast-feeding females. Sexually active patients must be willing to use an effective form of birth control.

Patients currently receiving other investigational agents.

Patients who have received allogeneic stem cell transplants.

Patients who have had prior therapy with trabectedin (ET-743, Yondelis).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01453283


Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Howard A Fine, M.D. National Cancer Institute (NCI)

Publications:
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Responsible Party: Brigitte C. Widemann, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT01453283    
Obsolete Identifiers: NCT00437047
Other Study ID Numbers: 070054
07-C-0054
First Posted: October 17, 2011    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: April 4, 2012
Keywords provided by National Institutes of Health Clinical Center (CC):
DNA Repair
Nucleotide Excision Repair
Trabectedine
Phase I
Sarcoma
Cytotoxic
Chemotherapy
Solid Tumor
Malignant Tumor
Rhabdomyosarcoma
Ewing Sarcoma
Neuroblastoma
Wilm's Tumor
Hepatic Tumor
Brain Tumor
Additional relevant MeSH terms:
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Trabectedin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents