Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Metastatic Rhabdomyosarcoma or Sarcoma - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003955

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy combined with radiation therapy in treating patients who have metastatic rhabdomyosarcoma or sarcoma.

Condition	Intervention	Phase
Sarcoma	Biological: dactinomycin Biological: filgrastim Biological: pegfilgrastim Biological: sargramostim Drug: cyclophosphamide Drug: irinotecan hydrochloride Drug: vincristine sulfate Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II "Up-Front Window Study" of Irinotecan (CPT-11) Followed by Multimodal, Multiagent, Therapy for Selected Children and Adolescents With Newly Diagnosed Stage 4/Clinical Group IV Rhabdomyosarcoma: An IRS-V Study

Resource links provided by NLM:

MedlinePlus related topics: Cancer Radiation Therapy Soft Tissue Sarcoma

Drug Information available for: Cyclophosphamide Dactinomycin Vincristine Irinotecan U 101440E Filgrastim Sargramostim Irinotecan hydrochloride Pegfilgrastim Vincristine sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	46
Study Start Date:	March 2001

Detailed Description:

OBJECTIVES:

Determine the response rate of patients with newly diagnosed high-risk metastatic stage IV/clinical group IV rhabdomyosarcoma treated with upfront window therapy comprising irinotecan and vincristine.
Determine the toxic effects of this regimen in these patients.
Determine the toxic effects of this regimen when given in alternating courses with vincristine, dactinomycin, and cyclophosphamide (VAC) as continuation therapy in patients with partial or complete response.
Determine the overall and failure-free survival of patients treated with irinotecan and vincristine followed by VAC alone or VAC alternating with vincristine and irinotecan plus radiotherapy.
Determine the pharmacokinetics of irinotecan and vincristine in these patients.

OUTLINE:

Upfront window therapy: Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 60 minutes on days 1-5 and 8-12. Treatment repeats every 21 days for a total of 2 courses. Patients experiencing partial or complete response proceed to regimen A. Patients experiencing stable or progressive disease proceed to regimen B.
- Regimen A: Patients receive vincristine IV over 1 minute weekly on weeks 6-13, 15-19, 23-27, 29, 32-35, 38-39, and 41; dactinomycin IV over 1 minute weekly on weeks 6, 12, 23, 29, 35, and 41; and cyclophosphamide IV over 30-60 minutes weekly on weeks 6, 12, 16, 19, 23, 29, 35, and 41. Patients also receive irinotecan IV over 1 hour daily, 5 days a week, on weeks 9, 10, 26, 27, 32, 33, 38, and 39 and undergo radiotherapy daily, 5 days a week, on weeks 15-22.
- Regimen B: Patients receive vincristine as in regimen A; dactinomycin IV over 1 minute weekly on weeks 6, 9, 12, 23, 26, 29, 32, 35, 38, and 41 and cyclophosphamide IV over 30-60 minutes weekly on weeks 6, 9, 12, 16, 19, 23, 26, 29, 32, 35, 38, and 41. Patients receive radiotherapy as in regimen A. Patients who do not receive upfront window irinotecan/vincristine therapy are treated with standard therapy.
Standard therapy: Patients receive vincristine IV over 1 minute weekly on weeks 0-13, 15-19, 23-27, 29, 32-35, 38, and 41; dactinomycin IV over 1 minute weekly on weeks 0, 6, 9, 12, 23, 26, 29, 32, 35, 38, and 41; and cyclophosphamide IV over 30-60 minutes weekly on weeks 0, 3, 6, 9, 12, 16, 19, 23, 26, 29, 32, 35, 38, and 41. Patients without evidence of intracranial extension receive radiotherapy once daily, 5 days a week, during weeks 15-22.

Patients with evidence of intracranial extension, or who require emergency radiotherapy, receive radiotherapy during weeks 0-6. Dactinomycin is withheld during radiotherapy. All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC) beginning 24 hours after completion of each course of chemotherapy and continuing until blood counts recover. Alternatively, patients may receive pegfilgrastim SC beginning 24-36 hours after completion of each course of chemotherapy and continuing until blood counts recover.

Patients are followed every 2 months for 1 year, every 4 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study within 9-24 months.

Eligibility

Ages Eligible for Study:	up to 49 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed metastatic stage IV/clinical group IV rhabdomyosarcoma, undifferentiated sarcoma, or ectomesenchymoma
- No metastatic embryonal tumors in patients under 10 years of age, regardless of primary site
- Metastatic tumors of parameningeal sites eligible
Bidimensionally measurable disease
No positive cerebrospinal fluid cytology or multiple intracranial metastases
Patients presenting with the following are only eligible for continuation therapy and may not receive irinotecan/vincristine upfront window therapy:
- Evidence of base of skull erosion or skull metastatic disease that displaces or indents the dura, compresses the brain parenchyma, or causes evidence of cranial nerve palsy
- Tumor that touches or displaces the spinal cord
- Evidence of intracranial primary tumor extension
- Tumors that could cause potentially life-threatening complications (e.g., renal, airway) with progression due to location and/or growth rate
- Requires emergency radiotherapy
- Lab values are consistent with disseminated intravascular coagulation

PATIENT CHARACTERISTICS:

Age:

Under 50 (alveolar rhabdomyosarcoma, undifferentiated sarcoma, and ectomesenchymoma patients)
10 to 49 (embryonal histology patients)

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics
Absolute neutrophil count greater than 1,000/mm^3*
Platelet count greater than 150,000/mm^3* NOTE: *Unless there is tumor involvement of bone marrow

Hepatic:

Bilirubin less than 1.5 mg/dL
PT, PTT, and fibrinogen less than 1.5 times upper limit of normal

Renal:

Creatinine less than 1.2 mg/dL

Other:

Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy

Endocrine therapy:

Prior steroids allowed

Radiotherapy:

See Disease Characteristics
No prior radiotherapy

Surgery:

No more than 42 days since prior initial surgical procedure, including biopsy for diagnosis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003955

Show 237 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Alberto S. Pappo, MD

Texas Children's Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Pappo AS, Lyden E, Breitfeld P, Donaldson SS, Wiener E, Parham D, Crews KR, Houghton P, Meyer WH; Children's Oncology Group. Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children's Oncology Group. J Clin Oncol. 2007 Feb 1;25(4):362-9.

Soft Tissue Sarcoma Committee of the Children's Oncology Group; Lager JJ, Lyden ER, Anderson JR, Pappo AS, Meyer WH, Breitfeld PP. Pooled analysis of phase II window studies in children with contemporary high-risk metastatic rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol. 2006 Jul 20;24(21):3415-22.

Study ID Numbers:	CDR0000067154, COG-D9802, IRS-D9802, CCG-D9802, POG-D9802
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00003955 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

embryonal childhood rhabdomyosarcoma
alveolar childhood rhabdomyosarcoma
metastatic childhood soft tissue sarcoma
childhood malignant mesenchymoma

previously untreated childhood rhabdomyosarcoma
adult rhabdomyosarcoma
adult malignant mesenchymoma
stage IV adult soft tissue sarcoma

Study placed in the following topic categories:

Immunologic Factors
Irinotecan
Vincristine
Rhabdomyosarcoma, Childhood
Antimitotic Agents
Cyclophosphamide
Immunosuppressive Agents
Camptothecin
Neoplasms, Connective and Soft Tissue
Anti-Bacterial Agents

Malignant Mesenchymal Tumor
Soft Tissue Sarcomas
Dactinomycin
Tubulin Modulators
Sarcoma
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents
Rhabdomyosarcoma

Additional relevant MeSH terms:

Neoplasms, Muscle Tissue
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Irinotecan
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Neoplasms, Connective and Soft Tissue
Anti-Bacterial Agents
Dactinomycin
Therapeutic Uses
Alkylating Agents
Nucleic Acid Synthesis Inhibitors

Rhabdomyosarcoma
Neoplasms by Histologic Type
Myosarcoma
Mitosis Modulators
Vincristine
Enzyme Inhibitors
Antimitotic Agents
Immunosuppressive Agents
Camptothecin
Pharmacologic Actions
Protein Synthesis Inhibitors
Neoplasms
Tubulin Modulators
Myeloablative Agonists
Sarcoma

ClinicalTrials.gov processed this record on July 02, 2009