Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma - Full Text View

Purpose

This randomized phase III trial is comparing two different combination chemotherapy regimens to see how well each works in treating patients with previously untreated rhabdomyosarcoma or sarcoma. Drugs used in chemotherapy, such as dactinomycin, cyclophosphamide, vincristine, and topotecan, use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective in treating rhabdomyosarcoma.

Condition	Intervention	Phase
Adult Malignant Mesenchymoma Adult Rhabdomyosarcoma Alveolar Childhood Rhabdomyosarcoma Childhood Malignant Mesenchymoma Embryonal Childhood Rhabdomyosarcoma Embryonal-botryoid Childhood Rhabdomyosarcoma Nonmetastatic Childhood Soft Tissue Sarcoma Previously Untreated Childhood Rhabdomyosarcoma Stage I Adult Soft Tissue Sarcoma Stage II Adult Soft Tissue Sarcoma Stage III Adult Soft Tissue Sarcoma	Biological: dactinomycin Drug: vincristine sulfate Drug: cyclophosphamide Procedure: therapeutic conventional surgery Radiation: radiation therapy Drug: topotecan hydrochloride Biological: filgrastim Biological: sargramostim Other: laboratory biomarker analysis	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized Study of Vincristine, Actinomycin-D, and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine, Topotecan and Cyclophosphamide for Patients With Intermediate Risk Rhabdomyosarcoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Soft Tissue Sarcoma

Drug Information available for: Cyclophosphamide Dactinomycin Vincristine sulfate Sulfate ion Topotecan hydrochloride Filgrastim Sargramostim Topotecan Lenograstim Granulocyte colony-stimulating factor

Genetic and Rare Diseases Information Center resources: Malignant Mesenchymal Tumor Soft Tissue Sarcoma Liver Cancer

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:

Long-term failure-free survival (FFS) between the two treatment groups [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival between treatments [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Rate of second look surgery [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Proportion of patients rendered tumor-free or with microscopic tumor only [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Estimation of the rate of local failure for the patients who undergo second look surgery [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Done using standard cumulative incidence curves.


Enrollment:	702
Study Start Date:	September 2002
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Vincristine sulfate IV once a wk on wks 0-12, 15, 18-24, 27, 30-36, and 39. Dactinomycin IV once a wk on wks 0, 3, 6, 9, 12, 21, 24, 27, 30, 33, 36, and 39. Cyclophosphamide IV once a wk on wks 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, and 39. After 12 weeks of chemotherapy, depending on tumor shrinkage, pts may undergo surgery. After recovery from therapeutic conventional surgery, patients receive radiation therapy once a day, 5 days a wk, during wks 12-18. For pt receiving radiotherapy during wks 0-6, dactinomycin is omitted during wks 3 and 6 and during wks 15 and 18. For patients receiving radiotherapy during wks 12-18, dactinomycin is omitted during wks 15 and 18. Patients with adequate response at wk 24 continue chemotherapy during wks 24-39. All pts receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery.	Biological: dactinomycin Given IV Other Names: ACT-D actinomycin C1 AD Cosmegen DACT Drug: vincristine sulfate Given IV Other Names: leurocristine sulfate VCR Vincasar PFS Drug: cyclophosphamide Given IV Other Names: CPM CTX Cytoxan Endoxan Endoxana Procedure: therapeutic conventional surgery Undergo surgery Radiation: radiation therapy Undergo radiotherapy Other Names: irradiation radiotherapy therapy, radiation Biological: filgrastim Given SC Other Names: G-CSF Neupogen Biological: sargramostim Given SC Other Names: GM-CSF Leukine Prokine Other: laboratory biomarker analysis Correlative studies
Experimental: Arm II Patients receive treatment as in arm I, except dactinomycin is replaced with topotecan hydrochloride IV over 15-30 minutes daily for 5 days during weeks 3, 9, 21, 27, 33, and 39. All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery.	Drug: vincristine sulfate Given IV Other Names: leurocristine sulfate VCR Vincasar PFS Drug: cyclophosphamide Given IV Other Names: CPM CTX Cytoxan Endoxan Endoxana Procedure: therapeutic conventional surgery Undergo surgery Radiation: radiation therapy Undergo radiotherapy Other Names: irradiation radiotherapy therapy, radiation Drug: topotecan hydrochloride Given IV Other Names: hycamptamine Hycamtin SKF S-104864-A TOPO Biological: filgrastim Given SC Other Names: G-CSF Neupogen Biological: sargramostim Given SC Other Names: GM-CSF Leukine Prokine Other: laboratory biomarker analysis Correlative studies

Arms

Assigned Interventions

Experimental: Arm I

Vincristine sulfate IV once a wk on wks 0-12, 15, 18-24, 27, 30-36, and 39. Dactinomycin IV once a wk on wks 0, 3, 6, 9, 12, 21, 24, 27, 30, 33, 36, and 39. Cyclophosphamide IV once a wk on wks 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, and 39. After 12 weeks of chemotherapy, depending on tumor shrinkage, pts may undergo surgery. After recovery from therapeutic conventional surgery, patients receive radiation therapy once a day, 5 days a wk, during wks 12-18. For pt receiving radiotherapy during wks 0-6, dactinomycin is omitted during wks 3 and 6 and during wks 15 and 18. For patients receiving radiotherapy during wks 12-18, dactinomycin is omitted during wks 15 and 18. Patients with adequate response at wk 24 continue chemotherapy during wks 24-39. All pts receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery.

Biological: dactinomycin

Given IV

Other Names:

ACT-D
actinomycin C1
AD
Cosmegen
DACT

Drug: vincristine sulfate

Given IV

Other Names:

leurocristine sulfate
VCR
Vincasar PFS

Drug: cyclophosphamide

Given IV

Other Names:

CPM
CTX
Cytoxan
Endoxan
Endoxana

Procedure: therapeutic conventional surgery

Undergo surgery

Radiation: radiation therapy

Undergo radiotherapy

Other Names:

irradiation
radiotherapy
therapy, radiation

Biological: filgrastim

Given SC

Other Names:

G-CSF
Neupogen

Biological: sargramostim

Given SC

Other Names:

GM-CSF
Leukine
Prokine

Other: laboratory biomarker analysis

Correlative studies

Experimental: Arm II

Patients receive treatment as in arm I, except dactinomycin is replaced with topotecan hydrochloride IV over 15-30 minutes daily for 5 days during weeks 3, 9, 21, 27, 33, and 39.

All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery.

Drug: vincristine sulfate

Given IV

Other Names:

leurocristine sulfate
VCR
Vincasar PFS

Drug: cyclophosphamide

Given IV

Other Names:

CPM
CTX
Cytoxan
Endoxan
Endoxana

Procedure: therapeutic conventional surgery

Undergo surgery

Radiation: radiation therapy

Undergo radiotherapy

Other Names:

irradiation
radiotherapy
therapy, radiation

Drug: topotecan hydrochloride

Given IV

Other Names:

hycamptamine
Hycamtin
SKF S-104864-A
TOPO

Biological: filgrastim

Given SC

Other Names:

G-CSF
Neupogen

Biological: sargramostim

Given SC

Other Names:

GM-CSF
Leukine
Prokine

Other: laboratory biomarker analysis

Correlative studies

Show Detailed Description

Eligibility


Ages Eligible for Study:	up to 49 Years (Child, Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically proven disease of any of the following types:
- Non metastatic alveolar rhabdomyosarcoma
  - Stage I, II, or III; Clinical Group I, II, or III
- Stage II or III, Clinical Group III embryonal rhabdomyosarcoma
  - Botryoid
  - Spindle cell
- Under 10 years, stage IV, Clinical Group IV embryonal rhabdomyosarcoma
  - Botryoid
  - Spindle cell
- Undifferentiated sarcoma
  - Stage I, II, or III; Clinical Group I, II, or III
- Ectomesenchymoma
  - Stage I, II, or III; Clinical Group I, II, or III, with alveolar features
  - Under 10 years, Stage IV, Clinical Group IV, with embryonal features
No more than 6 weeks since initial surgical procedure (e.g., biopsy) giving the definitive diagnosis
No parameningeal rhabdomyosarcoma with positive CSF cytology or multiple intracranial metastases
Bilirubin no greater than 1.5 mg/dL
Creatinine normal* for age
Not pregnant or nursing
Fertile patients must use effective contraception
No prior chemotherapy
Prior steroids allowed
No prior radiotherapy
See Disease Characteristics

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003958

Locations


United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Carola Arndt	Children's Oncology Group

More Information


Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00003958 History of Changes
Other Study ID Numbers:	D9803 NCI-2012-02302 IRS-D9803 COG-D9803 POG-D9803 CDR0000067157 CCG-D9803 U10CA098543
Study First Received:	November 1, 1999
Last Updated:	June 13, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Sarcoma Rhabdomyosarcoma Rhabdomyosarcoma, Embryonal Liver Neoplasms Mesenchymoma Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Myosarcoma Neoplasms, Muscle Tissue Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Liver Diseases Neoplasms, Complex and Mixed	Cyclophosphamide Vincristine Topotecan Dactinomycin Lenograstim Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 26, 2016