Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma

Stage III Adult Soft Tissue Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003958
• Other study ID #: D9803
• Secondary ID: NCI-2012-02302IR
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: June 13, 2013
• Start date: September 2002

Study information

• Verified date: June 2013
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 702
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 49 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Malignant Mesenchymoma
• Adult Rhabdomyosarcoma
• Alveolar Childhood Rhabdomyosarcoma
• Childhood Malignant Mesenchymoma
• Embryonal Childhood Rhabdomyosarcoma
• Embryonal-botryoid Childhood Rhabdomyosarcoma
• Liver Neoplasms
• Nonmetastatic Childhood Soft Tissue Sarcoma
• Previously Untreated Childhood Rhabdomyosarcoma
• Rhabdomyosarcoma
• Sarcoma
• Stage I Adult Soft Tissue Sarcoma
• Stage II Adult Soft Tissue Sarcoma
• Stage III Adult Soft Tissue Sarcoma

Intervention

Biological:
• dactinomycin
Given IV

Drug:
• vincristine sulfate
Given IV
• cyclophosphamide
Given IV

Procedure:
• therapeutic conventional surgery
Undergo surgery

Radiation:
• radiation therapy
Undergo radiotherapy

Drug:
• topotecan hydrochloride
Given IV

Biological:
• filgrastim
Given SC
• sargramostim
Given SC

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Children's Oncology Group	Arcadia	California

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Long-term failure-free survival (FFS) between the two treatment groups		Up to 5 years	No
Secondary	Overall survival between treatments		Up to 5 years	No
Secondary	Rate of second look surgery		Week 12	No
Secondary	Proportion of patients rendered tumor-free or with microscopic tumor only		Week 12	No
Secondary	Estimation of the rate of local failure for the patients who undergo second look surgery	Done using standard cumulative incidence curves.	Week 12	No