Tabectedin to Treat Children and Adolescents With Cancer

NCT01453283 | Completed Phase 1

• 2 other identifiers: 07005407-C-0054
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumors

Keywords

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

Interventions

Trabectedin (ecteinascidin-743, ET-743, YONDELIS [R]) DRUG

Eligibility Criteria

• Age: 4 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Gillet LC, Scharer OD. Molecular mechanisms of mammalian global genome nucleotide excision repair. Chem Rev. 2006 Feb;106(2):253-76. doi: 10.1021/cr040483f. No abstract available.

  PMID: 16464005 BACKGROUND

• Suk R, Gurubhagavatula S, Park S, Zhou W, Su L, Lynch TJ, Wain JC, Neuberg D, Liu G, Christiani DC. Polymorphisms in ERCC1 and grade 3 or 4 toxicity in non-small cell lung cancer patients. Clin Cancer Res. 2005 Feb 15;11(4):1534-8. doi: 10.1158/1078-0432.CCR-04-1953.

  PMID: 15746057 BACKGROUND

• Aune GJ, Furuta T, Pommier Y. Ecteinascidin 743: a novel anticancer drug with a unique mechanism of action. Anticancer Drugs. 2002 Jul;13(6):545-55. doi: 10.1097/00001813-200207000-00001.

  PMID: 12172500 BACKGROUND

MeSH Terms

Conditions

Sarcoma; Neoplasms; Rhabdomyosarcoma; Sarcoma, Ewing; Neuroblastoma; Wilms Tumor; Carcinoma, Hepatocellular; Brain Neoplasms

Interventions

Trabectedin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Myosarcoma; Neoplasms, Muscle Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Adenocarcinoma; Carcinoma; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Howard A Fine, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: October 1, 2011
• First Posted: October 17, 2011
• Study Start: December 20, 2006
• Primary Completion: October 11, 2011
• Study Completion: October 11, 2011
• Last Updated: July 2, 2017

Record last verified: 2012-04-04

Locations

US (1)