Combination Chemotherapy, Surgery, and Radiation Therapy in Treating Children With Advanced Soft Tissue Sarcoma

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00002804

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

115

Duration (Months)

4.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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, surgery, and radiation therapy in treating children who have advanced soft tissue sarcoma.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Biological: filgrastim Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: mesna Drug: vincristine sulfate Procedure: conventional surgery Radiation: brachytherapy Radiation: low-LET cobalt-60 gamma ray therapy Radiation: low-LET electron therapy Radiation: low-LET photon therapy	Phase 2

Detailed Description

OBJECTIVES: I. Assess the response to vincristine/ifosfamide/doxorubicin (VID) with granulocyte colony-stimulating factor support in children with newly diagnosed, inoperable or metastatic non-rhabdomyosarcoma soft tissue sarcomas. II. Estimate the 2-year and event-free survival rates in children treated with VID plus radiotherapy and/or surgery. III. Establish a bank of frozen tumor and peripheral blood tissue for use in further molecular studies.

OUTLINE: The following acronyms are used: DOX Doxorubicin, NSC-123127 G-CSF Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629 IFF Ifosfamide, NSC-109724 Mesna Mercaptoethane sulfonate, NSC-113891 VCR Vincristine, NSC-67574 VID VCR/IFF/DOX Induction: 3-Drug Combination Chemotherapy. VID. Local Control: Surgery and/or Radiotherapy plus 3-Drug Combination Chemotherapy. Excision of the primary tumor and pulmonary metastases; and/or irradiation of the primary tumor and pulmonary metastases using x-rays or Co60 beam energies of at least 4 MV (electrons or iridium-192 implant allowed for boost); plus VID. Continuation: 3-Drug Combination Chemotherapy. VID.

PROJECTED ACCRUAL: A total of 40 patients will be entered over 2.7 years if there are at least 7 responses in the first 20 patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study of Neoadjuvant Vincristine, Ifosfamide, Doxorubicin, and AND G-CSF in Children With Advanced Stage Non-Rhabdomyosarcoma Soft Tissue Sarcomas

Study Start Date :

Sep 1, 1996

Actual Primary Completion Date :

Jun 1, 2000

Actual Study Completion Date :

Apr 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemotherapy Regimen Induction (Weeks 1-6) Vincristine sulfate (1.5 mg/m2) day 1, Ifosfamide (3 grams/m2) days 1-3, Doxorubicin (30 mg/m2) days 1-2, filgrastim day 4. Weeks 2 and 3 - Vincristine sulfate (1.5 mg/m2) IV day 1, week 5 no chemotherapy. Evaluate for response. Local Control (Weeks 7-13) Conventional surgery and radiation therapy. Vincristine sulfate (1.5 mg/m2) IV day 1, Ifosfamide (3 grams/m2) days 1-3, Doxorubicin (30 mg/m2) days 1-2, filgrastim day 4. Treatment continues per protocol.	Biological: filgrastim Other Names: Granulocyte-Colony Stimulating Factor Neupogen G-CSF Drug: doxorubicin hydrochloride Other Names: Adriamycin NSC#123127 Drug: ifosfamide Other Names: Isophosphamide IFEX Drug: mesna Other Names: Sodium 2-Mercaptoethane Sulfonate Mesnex Urimetexan NSC#113891 Drug: vincristine sulfate Other Names: VCR Oncovin NSC#67574 Procedure: conventional surgery Radiation: brachytherapy Radiation: low-LET cobalt-60 gamma ray therapy Radiation: low-LET electron therapy Radiation: low-LET photon therapy

Arm

Intervention/Treatment

Experimental: Chemotherapy Regimen

Induction (Weeks 1-6) Vincristine sulfate (1.5 mg/m2) day 1, Ifosfamide (3 grams/m2) days 1-3, Doxorubicin (30 mg/m2) days 1-2, filgrastim day 4. Weeks 2 and 3 - Vincristine sulfate (1.5 mg/m2) IV day 1, week 5 no chemotherapy. Evaluate for response. Local Control (Weeks 7-13) Conventional surgery and radiation therapy. Vincristine sulfate (1.5 mg/m2) IV day 1, Ifosfamide (3 grams/m2) days 1-3, Doxorubicin (30 mg/m2) days 1-2, filgrastim day 4. Treatment continues per protocol.

Biological: filgrastim

Other Names:

Granulocyte-Colony Stimulating Factor

Neupogen

G-CSF

Drug: doxorubicin hydrochloride

Other Names:

Adriamycin

NSC#123127

Drug: ifosfamide

Other Names:

Isophosphamide

IFEX

Drug: mesna

Other Names:

Sodium 2-Mercaptoethane Sulfonate

Mesnex

Urimetexan

NSC#113891

Drug: vincristine sulfate

Other Names:

VCR

Oncovin

NSC#67574

Procedure: conventional surgery

Radiation: brachytherapy

Radiation: low-LET cobalt-60 gamma ray therapy

Radiation: low-LET electron therapy

Radiation: low-LET photon therapy

Outcome Measures

Primary Outcome Measures

Estimate the response rate to the combination of vincristine, ifosfamide, and doxorubicin (VID), with G-CSF support []
To estimate the response rate to the combination of vincristine, ifosfamide, and doxorubicin (VID), with G-CSF support, in children with newly diagnosed inoperable or metastatic non-rhabdomyosarcoma soft tissue sarcomas.

Secondary Outcome Measures

Event-free Survival []
To estimate the 2-year survival and event-free survival of children treated with VID in combination with radiotherapy and/or surgery
Establish a bank of frozen tissue (tumor and peripheral blood) []
To establish a bank of frozen tissue (tumor and peripheral blood) for use in further molecular studies.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Biopsy proven non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) Evaluable residual tumor after initial biopsy or excision required Registration required within 42 days of definitive diagnosis Grade II/III, unresectable or metastatic disease The following histologies exclude: Angiofibroma of the nasopharynx Mesothelioma Desmoid tumor Peripheral neuroepithelioma Desmoplastic small cell tumor Rhabdomyosarcoma Extraosseous

Ewing's sarcoma Undifferentiated sarcoma Kaposi's sarcoma Grade 1 NRSTS, including:

Angiomatoid malignant fibrous histiocytoma Dermatofibrosarcoma protuberans Myxoid and well-differentiated liposarcoma Well-differentiated and infantile hemangiopericytoma Well-differentiated malignant peripheral nerve sheath tumor

PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Not specified Hematopoietic:

Not specified Hepatic: Not specified Renal: Creatinine normal for age No hydronephrosis Cardiovascular: Shortening fraction greater than 28% Other: No HIV infection Not pregnant or nursing Effective contraception required of fertile women

PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy No prior nephrectomy (surgical correction of hydronephrosis allowed)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
2	MBCCOP - LSU Medical Center	New Orleans	Louisiana	United States	70112
3	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-2794
4	Medical City Dallas Hospital	Dallas	Texas	United States	75230
5	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas	United States	78236-5300
6	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
7	Cancer Center, University of Virginia HSC	Charlottesville	Virginia	United States	22908
8	University of Puerto Rico School of Medicine Medical Sciences Campus	San Juan		Puerto Rico	00936-5067
9	Clinique de Pediatrie	Geneva		Switzerland	1211