Clinical trial · Interventional
Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
A Randomized Phase 3 Study of Vincristine, Dactinomycin, Cyclophosphamide (VAC) Alternating With Vincristine and Irinotecan (VI) Versus VAC/VI Plus Temsirolimus (TORI, Torisel, NSC# 683864) in Patients With Intermediate Risk (IR) Rhabdomyosarcoma (RMS)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This randomized phase III trial studies how well combination chemotherapy (vincristine sulfate, dactinomycin, cyclophosphamide alternated with vincristine sulfate and irinotecan hydrochloride or vinorelbine) works compared to combination chemotherapy plus temsirolimus in treating patients with rhabdomyosarcoma (cancer that forms in the soft tissues, such as muscle), and has an intermediate chance of coming back after treatment (intermediate risk). Drugs used work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Combination chemotherapy and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether chemotherapy plus temsirolimus is more effective than chemotherapy alone in treating patients with intermediate-risk rhabdomyosarcoma.
Conditions
Conditions (6)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Alveolar Rhabdomyosarcoma | Alveolar Rhabdomyosarcoma | ONTOLOGY_EXACT | 0.90 |
| Botryoid-Type Embryonal Rhabdomyosarcoma | Botryoid-Type Embryonal Rhabdomyosarcoma | ONTOLOGY_EXACT | 0.90 |
| Embryonal Rhabdomyosarcoma | Embryonal Rhabdomyosarcoma | ONTOLOGY_EXACT | 0.90 |
| Rhabdomyosarcoma | Rhabdomyosarcoma | ONTOLOGY_EXACT | 0.90 |
| Sclerosing Rhabdomyosarcoma | Sclerosing Rhabdomyosarcoma | ONTOLOGY_EXACT | 0.98 |
| Spindle Cell Rhabdomyosarcoma | Spindle Cell Rhabdomyosarcoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (9)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Dactinomycin | Biological | Dactinomycin | ALIAS |
| Irinotecan Hydrochloride | Drug | Irinotecan | ALIAS |
| Laboratory Biomarker Analysis | Other | — | UNRESOLVED |
| Questionnaire Administration | Other | — | UNRESOLVED |
| Radiation Therapy | Radiation | — | UNRESOLVED |
| Temsirolimus | Drug | Temsirolimus | ALIAS |
| Vincristine Sulfate | Drug | Vincristine | ALIAS |
Design
Arms and outcomes
Arms (3)
- type
- EXPERIMENTAL
- label
- Regimen A (VAC/VI)
- description
- Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. Patients also undergo primary site RT beginning at week 13 or metastatic site RT beginning at week 43 for up to 6.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then receive vinorelbine IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide PO QD on days 1-28. Cycles repeats every 28 days for 24 weeks in the absence of disease progression or unacceptable toxicity.
- interventionNames
- Drug: Cyclophosphamide
- Biological: Dactinomycin
- Drug: Irinotecan Hydrochloride
- Other: Laboratory Biomarker Analysis
- Other: Questionnaire Administration
- Radiation: Radiation Therapy
- Drug: Vincristine Sulfate
- type
- EXPERIMENTAL
- label
- Regimen B (VAC/VI/temsirolimus)
Eligibility
Eligibility (as posted)
- Sex
- All
- Maximum age
- 40 Years
Show eligibility criteria text
Inclusion Criteria:
* Feasibility Phase: Patients must be \< 21 years of age at the time of enrollment; please note: the feasibility phase is complete, effective with amendment #1
* Efficacy Phase: Patients must be =\< 40 years of age at the time of enrollment
* Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study based upon stage, group, and age, as below
* RMS types included under embryonal rhabdomyosarcoma (ERMS) include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2013 World Health Organization (WHO) classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant); classification of alveolar rhabdomyosarcoma (ARMS) in the 2013 WHO classification is the same as in the ICR and includes classic and solid variants
* ERMS
* Stage 1, group III (non-orbit)
* Stage 3, group I/II
* Stage 2/3, group III
* Stage 4, group IV, \< 10 years old
* ARMS:
* Stages 1-3, groups I-III
* Specimen Submission: Patients must have sufficient tissue available for the required biology study
* Lansky performance status score \>= 50 for patients =\< 16 years of age; Karnofsky performance status score \>= 50 for patients \> 16 years of age
* Peripheral absolute neutrophil count (ANC) \>= 750/uL
* Platelet count \>= 75,000/uL
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
* 1 month to \< 6 months old: 0.4 mg/dl (male), 0.4 mg/dl (female)
* 6 months to \< 1 year old: 0.5 mg/dl (male), 0.5 mg/dl (female)
* 1 to \< 2 years old: 0.6 mg/dl (male), 0.6 mg/dl (female)
* 2 to \< 6 years old: 0.8 mg/dl (male), 0.8 mg/dl (female)
* 6 to \< 10 years old: 1 mg/dl (male), 1 mg/dl (female)
* 10 to \< 13 years old: 1.2 mg/dl (male), 1.2 mg/dl (female)
* 13 to \< 16 years old: 1.5 mg/dl (male), 1.4 mg/dl (female)
* \>= 16 years old: 1.7 mg/dl (male), 1.4 mg/dl (female)
* Patients with an elevated serum creatinine due to obstructive hydronephrosis secondary to tumor are still eligible; however, patients with urinary tract obstruction by tumor must have unimpeded urinary flow established via diversion (i.e. percutaneous nephrostomies or ureteric stents) of the urinary tract
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
* Patients who have previously received temsirolimus, another mTOR inhibitor, or any other investigational agent
* Patients who have received any chemotherapy (excluding steroids) and/or RT prior to this enrollment
* Patients with uncontrolled hyperglycemia
* Patients with uncontrolled hyperlipidemia
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for at least 3 months after treatment is completed
* Female patients who are pregnant are not eligible since fetal toxicities or teratogenic effects have been noted for several of the study drugs; Note: A pregnancy test is required for female patients of childbearing potential prior to study entry
* Lactating females who plan to breastfeed their infants are not eligibleReferences
Publications (3)
- DERIVEDWinsnes K, Bradley JA, Gao Z, Gupta AA, Rothstein DH, Shenoy A, Venkatramani R, Xue W, Arndt C. Intermediate Risk Rhabdomyosarcoma in Very Young Children (Less Than or Equal to 24 Months) Treated on the Prior Children's Oncology Group Protocol ARST1431. Pediatr Blood Cancer. 2026 Jun;73(6):e70293. doi: 10.1002/1545-5017.70293. Epub 2026 Mar 31. PMID 41914453
- DERIVEDGupta AA, Xue W, Harrison DJ, Hawkins DS, Dasgupta R, Wolden S, Shulkin B, Qumseya A, Routh JC, MacDonald T, Feinberg S, Crompton B, Rudzinski ER, Arnold M, Venkatramani R. Addition of temsirolimus to chemotherapy in children, adolescents, and young adults with intermediate-risk rhabdomyosarcoma (ARST1431): a randomised, open-label, phase 3 trial from the Children's Oncology Group. Lancet Oncol. 2024 Jul;25(7):912-921. doi: 10.1016/S1470-2045(24)00255-9. PMID 38936378
- DERIVEDde Traux de Wardin H, Dermawan JK, Vanoli F, Jiang SC, Singer S, Chi P, Tap W, Wexler LH, Antonescu CR. NF1-Driven Rhabdomyosarcoma Phenotypes: A Comparative Clinical and Molecular Study of NF1-Mutant Rhabdomyosarcoma and NF1-Associated Malignant Triton Tumor. JCO Precis Oncol. 2024 Apr;8:e2300597. doi: 10.1200/PO.23.00597. PMID 38603649