search
Back to results

Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma

Primary Purpose

Adult Malignant Mesenchymoma, Adult Rhabdomyosarcoma, Alveolar Childhood Rhabdomyosarcoma

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
dactinomycin
vincristine sulfate
cyclophosphamide
therapeutic conventional surgery
radiation therapy
topotecan hydrochloride
filgrastim
sargramostim
laboratory biomarker analysis
Sponsored by
Children's Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Malignant Mesenchymoma

Eligibility Criteria

undefined - 49 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Oncology Group

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I

Arm II

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Long-term failure-free survival (FFS) between the two treatment groups

Secondary Outcome Measures

Overall survival between treatments
Rate of second look surgery
Proportion of patients rendered tumor-free or with microscopic tumor only
Estimation of the rate of local failure for the patients who undergo second look surgery
Done using standard cumulative incidence curves.

Full Information

First Posted
November 1, 1999
Last Updated
June 13, 2013
Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00003958
Brief Title
Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
September 2002 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
OBJECTIVES: I. Compare the early response rates, failure-free survival, and survival of patients with intermediate-risk rhabdomyosarcoma treated with surgery, radiotherapy, and vincristine, dactinomycin, and cyclophosphamide (VAC) vs VAC alternating with vincristine, topotecan, and cyclophosphamide. II. Compare the acute and late effects of these two treatment regimens in these patients. III. Determine the rate of second-look surgery in selected patients with bulk residual tumor at diagnosis (i.e., Clinical Group III) and the proportion of these that render the patient tumor free or with microscopic tumor only. IV. Determine the rate of local failure in selected patients with bulk residual tumors at diagnosis (i.e., Clinical Group III) who, after second-look resection, have response-adjusted radiotherapy dose reduction. V. Determine if preoperative radiotherapy followed by second-look surgery is feasible for selected patients with bulk residual disease (i.e., Clinical Group III) who respond poorly to induction chemotherapy. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease (embryonal histology, stage II or III, Clinical Group III vs embryonal histology, Clinical Group IV, less than 10 years of age vs alveolar or undifferentiated sarcoma histology, stage I, Clinical Group I vs alveolar or undifferentiated sarcoma histology, stage II or III, Clinical Group II or III). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive vincristine IV over 5-10 minutes once a week on weeks 0-12, 15, 18-24, 27, 30-36, and 39. Dactinomycin IV is administered over 15-20 minutes once a week on weeks 0, 3, 6, 9, 12, 21, 24, 27, 30, 33, 36, and 39. Cyclophosphamide IV is administered over 30-60 minutes once a week on weeks 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, and 39. After the initial 12 weeks of chemotherapy, depending on tumor shrinkage, patients may undergo surgery. After recovery from surgery, patients receive radiotherapy once a day, 5 days a week, during weeks 12-18. For patients receiving radiotherapy during weeks 0-6, dactinomycin is omitted during weeks 3 and 6 and administered during weeks 15 and 18. For patients receiving radiotherapy during weeks 12-18, dactinomycin is omitted during weeks 15 and 18. Patients showing an adequate response at week 24 continue chemotherapy during weeks 24-39. Patients with Clinical Group III tumors of a parameningeal site with documented evidence of intracranial extension receive radiotherapy within the first 2 weeks of the initiation of the first course of chemotherapy (day 0). Patients with Clinical Group II parameningeal tumors and Clinical Group III parameningeal tumors with base of skull erosion and/or cranial nerve palsy without evidence of intracranial extension receive radiotherapy on week 12 (day 84) or immediately thereafter. Patients with Clinical Group IV parameningeal tumors with distant metastases receive radiotherapy to the primary site on week 12 (day 84). Patients with distant metastases confined to one site may receive radiotherapy to the metastatic site concurrently with therapy to the primary site if it began within 2 weeks of the initiation of chemotherapy (day 0). Arm II: Patients receive treatment as in arm I, except dactinomycin is replaced with topotecan 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. Patients are followed every 1-2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
702 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm II
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
dactinomycin
Other Intervention Name(s)
ACT-D, actinomycin C1, AD, Cosmegen, DACT
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Other Intervention Name(s)
leurocristine sulfate, VCR, Vincasar PFS
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
therapeutic conventional surgery
Intervention Description
Undergo surgery
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
Undergo radiotherapy
Intervention Type
Drug
Intervention Name(s)
topotecan hydrochloride
Other Intervention Name(s)
hycamptamine, Hycamtin, SKF S-104864-A, TOPO
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF, Neupogen
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
sargramostim
Other Intervention Name(s)
GM-CSF, Leukine, Prokine
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Long-term failure-free survival (FFS) between the two treatment groups
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Overall survival between treatments
Time Frame
Up to 5 years
Title
Rate of second look surgery
Time Frame
Week 12
Title
Proportion of patients rendered tumor-free or with microscopic tumor only
Time Frame
Week 12
Title
Estimation of the rate of local failure for the patients who undergo second look surgery
Description
Done using standard cumulative incidence curves.
Time Frame
Week 12

10. Eligibility

Sex
All
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carola Arndt
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Oncology Group
City
Arcadia
State/Province
California
ZIP/Postal Code
91006-3776
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma

We'll reach out to this number within 24 hrs