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

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003958

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Sarcoma	Biological: dactinomycin Biological: filgrastim Biological: sargramostim Drug: cyclophosphamide Drug: topotecan hydrochloride Drug: vincristine sulfate Procedure: surgical procedure Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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 Surgery

Drug Information available for: Cyclophosphamide Dactinomycin Vincristine Topotecan hydrochloride Filgrastim Sargramostim Topotecan Vincristine sulfate

U.S. FDA Resources

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

Primary Outcome Measures:

Early response rate (ERR) (i.e., complete response/partial response [CR/PR]) at end of therapy & at 3, 5, and 10 yrs after completion of therapy [ Designated as safety issue: No ]
Failure-free survival (FFS) at end of therapy & at 3, 5, and 10 yrs after completion of therapy [ Designated as safety issue: No ]
Survival at end of therapy & at 3, 5, and 10 yrs after completion of therapy [ Designated as safety issue: No ]
Acute and late effects (e.g., sterility, second malignancy, radiation effects, and growth effects) of these regimens continuously for up to 10 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rate of second-look surgery in patients with bulk residual tumor at diagnosis and those who become "tumor free" or have microscopic tumor only and are treated with reduced dose radiation at the end of therapy [ Designated as safety issue: No ]
Rate of local failure in selected patients with bulk residual tumors at diagnosis who undergo second-look resection and response-adjusted radiotherapy dose reduction ongoing for up to 10 years [ Designated as safety issue: No ]
Preoperative radiotherapy followed by second-look surgery indicated for patients who respond poorly to induction chemotherapy [ Designated as safety issue: No ]
Define and compare clinical features (demographics such as age, disease site and stage, node involvement, or outcome) of patient subgroups with alveolar rhabdomyosarcoma whose tumors carry t(2;13), t(1;13) or neither transloc. at end of the study [ Designated as safety issue: No ]
Estimation of ERR, FFS, and survival of patients with alveolar rhabdomyosarcoma with t(2;13), t(1;13), or neither transloc. by pos. or neg. RTPCR on peripheral blood and marrow spec. at diagnosis and at end of tx [ Designated as safety issue: No ]

Estimated Enrollment:	518
Study Start Date:	September 2002

Show Detailed Description

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically proven disease of any of the following types:
- Nonmetastatic 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

PATIENT CHARACTERISTICS:

Age:

Under 50

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Bilirubin no greater than 1.5 mg/dL

Renal:

Creatinine normal* for age NOTE: *Patients with tumor obstruction causing creatinine elevation may be enrolled

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:

No prior radiotherapy

Surgery:

See Disease Characteristics

Contacts and Locations

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

Show 233 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Carola A. S. Arndt, MD

Mayo Clinic

More Information

Additional Information:

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

Publications:

Arndt CA, Stoner JA, Hawkins DS, Rodeberg DA, Hayes-Jordan AA, Paidas CN, Parham DM, Teot LA, Wharam MD, Breneman JC, Donaldson SS, Anderson JR, Meyer WH. Vincristine, Actinomycin, and Cyclophosphamide Compared With Vincristine, Actinomycin, and Cyclophosphamide Alternating With Vincristine, Topotecan, and Cyclophosphamide for Intermediate-Risk Rhabdomyosarcoma: Children's Oncology Group Study D9803. J Clin Oncol. 2009 Sep 21; [Epub ahead of print]

Arndt CA, Hawkins DS, Stoner JA, et al.: Randomized phase III trial comparing vincristine, actinomycin, cyclophosphamide (VAC) with VAC/V topotecan/cyclophosphamide (TC) for intermediate risk rhabdomyosarcoma (IRRMS). D9803, COG study. [Abstract] J Clin Oncol 25 (Suppl 18): A-9509, 528s, 2007.

Arndt C, Hawkins D, Anderson JR, Breitfeld P, Womer R, Meyer W. Age is a risk factor for chemotherapy-induced hepatopathy with vincristine, dactinomycin, and cyclophosphamide. J Clin Oncol. 2004 May 15;22(10):1894-901. Erratum in: J Clin Oncol. 2004 Aug 15;22(16):3434. Correction of dosage error in text.

Petricoin EF 3rd, Espina V, Araujo RP, Midura B, Yeung C, Wan X, Eichler GS, Johann DJ Jr, Qualman S, Tsokos M, Krishnan K, Helman LJ, Liotta LA. Phosphoprotein pathway mapping: akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival. Cancer Res. 2007 Apr 1;67(7):3431-40.

Study ID Numbers:	CDR0000067157, COG-D9803, CCG-D9803, POG-D9803, IRS-D9803
Study First Received:	November 1, 1999
Last Updated:	September 24, 2009
ClinicalTrials.gov Identifier:	NCT00003958 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

embryonal childhood rhabdomyosarcoma
alveolar childhood rhabdomyosarcoma
embryonal-botryoid childhood rhabdomyosarcoma
nonmetastatic childhood soft tissue sarcoma
childhood malignant mesenchymoma
previously untreated childhood rhabdomyosarcoma

adult rhabdomyosarcoma
adult malignant mesenchymoma
stage II adult soft tissue sarcoma
stage III adult soft tissue sarcoma
stage I adult soft tissue sarcoma

Additional relevant MeSH terms:

Neoplasms, Muscle Tissue
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
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
Pharmacologic Actions
Protein Synthesis Inhibitors
Neoplasms
Tubulin Modulators
Myeloablative Agonists
Sarcoma
Antineoplastic Agents, Alkylating
Topotecan

ClinicalTrials.gov processed this record on November 09, 2009