RhabdomyosarcomaPhase 2NCT06023641
Treatment of Newly Diagnosed Rhabdomyosarcoma Using Molecular Risk Stratification and Liposomal Irinotecan Based Therapy in Children With Intermediate and High Risk Disease
A Phase 2 study testing Vincristine, Dactinomycin and Cyclophosphamide in people with Rhabdomyosarcoma, run by St. Jude Children's Research Hospital at 3 sites in United States.
Trial summary
This is a phase II study to determine safety and efficacy of combining liposomal irinotecan with vincristine alternating with VAC in intermediate-risk patients, liposomal irinotecan with temozolomide and vincristine alternating with VAC in high-risk patients and the chemotherapy combinations when given with… Read more about this study
- Who is it for?
- Ages Up to 22 years
- Conditions the study is for
- Rhabdomyosarcoma
- What is being tested?
- Vincristine, Dactinomycin and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Mar 2024to Oct 2037
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Newly diagnosed participants with the diagnosis of rhabdomyosarcoma (RMS) of any subtype. This includes embryonal rhabdomyosarcoma (fusion negative), alveolar rhabdomyosarcoma (fusion positive), as well as spindle cell and sclerosing
- Must have either low-, intermediate-risk or high-risk disease, defined as:
- Low-risk: TP53 and MYOD1 negative AND
- Embryonal, congenital/infantile spindle cell, or spindle cell/sclerosing FOXO1 fusion negative histology
- Stage 1 Group I, Group II
- Stage 1 Group III orbital only
Show all 40Show fewer
- Stage 2 Group I, Group II
- Intermediate-risk: MYOD1 and TP53 negative AND
- Embryonal, congenital/infantile spindle cell, or spindle cell/sclerosing FOXO1 fusion negative histology o Stage 1 Group III non orbit o Stage 3 Group I/II
- o Stage 2/3 Group III
- Stage 4 Group IV and Oberlin 0-1
- Alveolar, spindle cell/sclerosing FOXO1 fusion positive histology
- Stage 1-3, Group I-III N0
- High-risk: All MYOD1 and TP53 mutant tumors regardless of stage and Group AND/OR
- Embryonal, congenital/infantile spindle cell or spindle cell/sclerosing FOXO1 fusion negative o Group IV ≥ 10 year of age and Oberlin ≥ 2
- Alveolar, spindle cell/sclerosing FOXO1 fusion positive
- N1
- Stage 4 Group IV
- See Appendices I and II for Staging and Clinical Grouping.
- Age < 22 years (eligible for enrollment until 22nd birthday)
- Performance level corresponding to ECOG score of 0, 1, or 2. The Lansky performance score should be used for participants < 16 years (see Appendix VII).
- Participant has received no prior radiotherapy or chemotherapy for rhabdomyosarcoma (excluding steroids) unless an emergency situation requires local tumor treatment (discuss with PI).
- Initiation of chemotherapy is planned within 6 weeks (42 days) of the definitive biopsy or surgical resection.
- Adequate bone marrow function defined as:
- Peripheral absolute neutrophil count (ANC) ≥ 750/μL
- Platelet count ≥ 75,000/μL (transfusion independent)
- Adequate liver function defined as total bilirubin < 1.5 x upper limit of normal (ULN) for age. Participants with biliary or hepatic primaries with bilirubin values greater than 1.5 x ULN may be enrolled on study if all other eligibility criteria are met.
- Adequate renal function defined as:
- Creatinine clearance or radioisotope GFR > 70 mL/min/1.732 or serum creatinine based on age as follows:
- Age Maximum serum creatinine (mg/dL) Male Female
- 1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5 Age Maximum serum creatinine (mg/dL)
- to < 2 years 0.6 0.6
- to < 6 years 0.8 0.8
- 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4 > 16 years 1.7 1.4
- The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR25 utilizing child length and stature. Data published by the CDC.
- Participants with urinary tract obstruction by tumor must meet the renal function criteria listed above AND must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract.
- Adequate pulmonary function defined as: no evidence of dyspnea at rest and a pulse oximetry > 94% if there is a clinical indication for determination. Pulmonary function tests are not required.
- Patients requiring emergency radiation therapy are eligible for enrollment on this trial. See Section 4.11 for radiation therapy guidelines.
- No evidence of active, uncontrolled infection.
- All participants and/or their parents or legal guardians must sign a written informed consent.
Who cannot join
- Patients who have received any chemotherapy (excluding steroids).
- Patients who have received prior full course RT at the primary site of disease. This does not exclude patients that received emergent radiation.
- Ongoing or history of non-infectious interstitial lung disease requiring significant medical intervention.
- 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. Female participants > 10 years of age or post-menarchal must have a negative serum or urine pregnancy test within 24 hours prior to beginning treatment.
- Lactating females who are or plan to breastfeed their infants are not eligible.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Not yet recruiting
Cook Children's Medical Center
Fort Worth, Texas, 76104-2796
Karen Albritton, MD, 682-885-4007, karen.albritton@cookchildrens.org
Karen Albritton
- Recruiting
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Alberto Pappo, MD, 901-595-2322, referralinfo@stjude.org
- Recruiting
Stanford University
Palo Alto, California, 94304
Raya Saab, MD, 650-497-8953, rsaab@stanford.edu
Raya Saab, MD
About this study
Official title: A Protocol for the Treatment of Newly Diagnosed Rhabdomyosarcoma Using Molecular Risk Stratification and Liposomal Irinotecan Based Therapy in Children With Intermediate and High Risk Disease
This is a phase II study to determine safety and efficacy of combining liposomal irinotecan with vincristine alternating with VAC in intermediate-risk patients, liposomal irinotecan with temozolomide and vincristine alternating with VAC in high-risk patients and the chemotherapy combinations when given with concomitant radiation therapy in intermediate and high risk patients.
Primary Objective
Read more
- Estimate event-free survival for intermediate-risk participants treated with VAC and vincristine and liposomal irinotecan (VLI) with the addition of maintenance therapy with vinorelbine and cyclophosphamide.
- Estimate the event-free survival for high-risk patients treated with VAC and vincristine, liposomal irinotecan, and temozolomide with the addition of maintenance therapy with vinorelbine and cyclophosphamide.
Secondary Objectives
- To assess the relation between pharmacogenetic variation in CEP72 genotype and vinca alkaloid (vincristine; vinorelbine) disposition in children with rhabdomyosarcoma.
- To assess the relation between the pharmacogenetic variation in drug metabolizing enzymes and drug transporters, and the pharmacokinetics of vinca alkaloids, liposomal irinotecan, and cyclophosphamide in children with rhabdomyosarcoma.
- To assess the extent of inter-patient variability in the pharmacokinetics of vinca alkaloids, liposomal irinotecan, and cyclophosphamide in children with rhabdomyosarcoma, and explore possible associations between drug disposition and patient specific covariates (e.g., age, sex, race, weight).
- Estimate the cumulative incidence of local recurrence and overall 3-year event-free survival in patients with low-risk disease, intermediate-risk disease or high-risk disease treated with either no adjuvant radiation or minimal volume radiation and compare these outcomes with the outcomes achieved on RMS13.
Read the detailed description
This is a phase II study to determine safety and efficacy of combining liposomal irinotecan with vincristine alternating with VAC in intermediate-risk patients, liposomal irinotecan with temozolomide and vincristine alternating with VAC in high-risk patients and the chemotherapy combinations when given with concomitant radiation therapy in intermediate and high risk patients. The dose of liposomal irinotecan for intermediate and high risk patients will be 160/mg/m2 on Day 1 based on the results and recommended phase 2 dose of the Phase I trial ONITT trial. The primary objective is to assess event-free survival (EFS). The sample size is determined based on a 2-year EFS estimate for each risk group, with a total study duration of 4 years for enrollment and 2 years of follow-up per patient.
The study employs a single-arm adaptive Phase II design, with an estimated 46 patients in the intermediate-risk group and 34 patients in the high-risk group, ensuring 80% power and a 5% Type I error rate. The trial will conclude once the last enrolled patient has completed 2 years of follow-up.
- Conditions
- Rhabdomyosarcoma
- Being tested
- Vincristine, Dactinomycin, Cyclophosphamide, Surgical Resection, Proton beam radiation or external beam radiation or brachytherapy
- Medical subject headings
- Rhabdomyosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VincristineDrug
Also called Oncovin
Low -risk Administer IV push over 1 minute (or infusion via minibag as per institutional standards) on Day 1 of Weeks 1,8, 15 (3) doses. The maximum dose is 2 mg for all participants.
Intermediate-risk Administer IV, over 1 minute, 3 doses, weekly on day1 High-risk Administer by IV infusion over 1 minute, 3 doses, weekly on day 1,8,15
DactinomycinDrug
Also called (actinomycin-D)
Low-risk Administer by slow IV push over 1-5 minutes on Day 1 of Weeks 1, (1) dose. The maximum dose is 2.5 mg for all participants.
Intermediate-risk Administer by slow IV over 1-5 minutes., 1 doses weekly on day 1 High-risk Administer by slow IV over 1-5 minutes, day1
CyclophosphamideDrug
Also called Cytoxan®.
Low-risk Administer by IV infusion over 30-60 minutes on Day 1, 91) dose, Mesna and hydration will be given with IV cyclophosphamide according to institutional standards.
Intermediate-risk Administer by IV infusion over 30-60 minutes, 1 dose, day 1 High-risk Administer by IV infusion over 30-60 minutes, 1 dose, day1
Surgical ResectionProcedure or surgery
Low, Intermediate and High-risk
Proton beam radiation or external beam radiation or brachytherapyProcedure or surgery
Low, Intermediate and High-risk
Liposomal irinotecanDrug
Also called (Onivyde®)
Intermediate and High-risk Administer by IV infusion over 90 minutes, 1 dose on day 1 Liposomal irinotecan should be premedicated with dexamethasone (or an equivalent corticosteroid) if not contraindicated. Premedication with diphenhydramine and an H2 receptor antagonist (i.e., famotidine) are also encouraged.
VinorelbineDrug
Also called Navelbine
Intermediate and High-risk Administer via slow IV push over 6-10 minutes (or infusion via minibag as per institutional standards) on Day 1 of Weeks 43-45, 47-49, 51-53, 55-57, 59-61, 63-65.
TemozolomideDrug
Also called Temodar
High-risk Administer PO (or by NG or G tube) 5 doses, on Days 1-5 When administering with liposomal irinotecan, administer temozolomide prior to liposomal irinotecan. Preferably, administer on an empty stomach (at least 1 hour before and 2 hours after food) to improve absorption. When using temozolomide capsules, round dose to the nearest 5 mg capsule. The capsule may be opened, and contents mixed with applesauce or apple juice. A compounded oral suspension is also available. If emesis occurs within 20 minutes of taking a dose of temozolomide, then the dose may be repeated once.
Filgrastim, peg-filgrastimDrug
Also called Neupogen
Low, Intermediate and High-risk:
Prophylactic myeloid growth factor support (Filgrastim or Pegfilgrastim) should be used after all VAC cycles for patients on the high-risk arm. Start myeloid growth factor support (for example, filgrastim 5 mcg/kg/dose SubQ daily until the ANC is ≥ 2000/μL after the expected nadir OR pegfilgrastim 0.1 mg/kg/dose [for patients < 45 kg] or 6 mg/dose [for patients ≥ 45 kg] SubQ x 1 dose) 24-48 hours after VAC cycles. Filgrastim may be continued without regard to VCR. Discontinue filgrastim at least 24 hours before the start of the next cycle. Prophylactic myeloid growth factor support should NOT be used after VLIT cycles or during maintenance chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Low -risk | Experimental | The participant will receive 12 weeks (4 cycles) of VAC chemotherapy (vincristine, dactinomycin and cyclophosphamide) followed by 12 weeks (4 cycles) of VA chemotherapy (vincristine, dactinomycin).
Each cycle of VAC/VA chemotherapy will last for 3 weeks, for a total of 12 weeks (VAC or VA will be given in Week 1 of each cycle and vincristine will be given Weeks 2 and 3). At week 12, the participant will have scans and tests to reevaluate your tumor's response to the treatment. After surgery and radiation, the participant will receive an additional 12 weeks (4 cycles) of the same chemotherapy without cyclophosphamide. Vincristine and dactinomycin, also called "VA". After 4 cycles of VA, The investigator will re-evaluate the tumor again at week 24 and the patient will not get any more chemotherapy, but will be closely watched for any signs of tumor recurrence. Receives: Drug: Vincristine; Drug: Dactinomycin; Drug: Cyclophosphamide; Procedure: Surgical Resection; Procedure: Proton beam radiation or external beam radiation or brachytherapy |
| Intermediate-risk | Experimental | The purpose of this part of the study is to find out if adding a drug called liposomal irinotecan (also called Onivyde) to standard chemotherapy/radiation/surgery will result in better treatment outcomes for patients with intermediate and high risk rhabdomyosarcoma. The investigators also want to find the best radiation dose to give for intermediate and high risk patients who have large tumors (> 5 cm).
The patient will receive 42 weeks of VAC chemotherapy (vincristine, actinomycin D/dactinomycin and cyclophosphamide) alternating with VLI chemotherapy (vincristine/liposomal irinotecan). The participant will also have surgery to remove the tumor and radiation therapy during this time. After this therapy is completed you will get an additional 6 months of maintenance chemotherapy with vinorelbine and oral (by mouth) cyclophosphamide. Receives: Drug: Vincristine; Drug: Dactinomycin; Drug: Cyclophosphamide; Procedure: Surgical Resection; Procedure: Proton beam radiation or external beam radiation or brachytherapy; Drug: Liposomal irinotecan; Drug: Vinorelbine; Drug: Filgrastim, peg-filgrastim |
| High-risk | Experimental | The purpose of this part of the study is to find out if adding a drug called liposomal irinotecan (also called Onivyde) to standard chemotherapy/radiation/surgery will result in better treatment outcomes for patients with high risk rhabdomyosarcoma. The investigator also want to find the best radiation dose to give for high risk patients who have large tumors (> 5 cm).
The patient will receive 42 weeks of VAC chemotherapy (vincristine, actinomycin D/dactinomycin and cyclophosphamide) alternating with VLIT chemotherapy (vincristine/liposomal irinotecan/temozolomide). Also having surgery to remove the participants tumor and radiation therapy during this time. After this therapy is completed the patient will get an additional 6 months of maintenance chemotherapy with vinorelbine and oral (by mouth) cyclophosphamide. Receives: Drug: Vincristine; Drug: Dactinomycin; Drug: Cyclophosphamide; Procedure: Surgical Resection; Procedure: Proton beam radiation or external beam radiation or brachytherapy; Drug: Liposomal irinotecan; Drug: Vinorelbine; Drug: Temozolomide; Drug: Filgrastim, peg-filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated doses (MTDs)
MTD is defined in the study as the highest treatment dose that would deliver desirable treatment effects without resulting in a target toxicity rate greater than 0.3. For each of three groups (intermediate-risk, high-risk, and intermediate-and-high-risk-with-early-radiation), we will employ the Bayesian optimal interval (BOIN) design to find the MTD.
Measured: 4 years
Event-free survival (EFS)
We will estimate the 2-year event-free survival for intermediate-risk and high-risk patients, which is the estimated probability of a patient not having any events within the 2-year follow-up. If an event, including local failure, distant failure, death or loss to follow-up occurs for a patient within 2-year, we call it failure, otherwise call it response.
Measured: 2 years post, off therapy
Local recurrence rate (LRR)
LRR is defined as a binary endpoint in the study. The local recurrence-free survival (LRFS) is defined as time from randomization to the earlier date of the first of local disease recurrence or death due to any cause. The distant failure will be considered to be the competing risk, patients for whom follow-up ended without clinical improvement will be censored. The goal of the local recurrence rate endpoint is to evaluate the 2-year LRR by comparing the administration of 59.4 GyRBE and 68 GyRBE for patients (pooled intermediate- and high-risk groups) with tumor size greater than or equal to 5cm meeting the eligibility criteria for randomization (no biliary tree or specific extremity cases).
.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2023
- Study start13 Mar 2024
- Primary completionOct 2034 (estimated)
- Study completionOct 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RhabdomyosarcomaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alberto Pappo, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06023641
- Sponsor's protocol ID
- RMS2021
- Other IDs
- NCI-2024-00701
- Status last verified
- Jun 2026
- First submitted
- 27 Aug 2023
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Protocol for the Treatment of Newly Diagnosed Rhabdomyosarcoma Using Molecular Risk Stratification and Liposomal Irinotecan Based Therapy in Children With Intermediate and High Risk Disease
- ClinicalTrials.gov ID
- NCT06023641
- Acronym / sponsor ID
- RMS2021
- Conditions
- Rhabdomyosarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- 13 Mar 2024 (actual)
- Primary completion
- Oct 2034 (estimated)
- Study completion
- Oct 2037 (estimated)
- First posted
- 5 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II study to determine safety and efficacy of combining liposomal irinotecan with vincristine alternating with VAC in intermediate-risk patients, liposomal irinotecan with temozolomide and vincristine alternating with VAC in high-risk patients and the chemotherapy combinations when given with concomitant radiation therapy in intermediate and high risk patients.
Primary Objective
- Estimate event-free survival for intermediate-risk participants treated with VAC and vincristine and liposomal irinotecan (VLI) with the addition of maintenance therapy with vinorelbine and cyclophosphamide.
- Estimate the event-free survival for high-risk patients treated with VAC and vincristine, liposomal irinotecan, and temozolomide with the addition of maintenance therapy with vinorelbine and cyclophosphamide.
Secondary Objectives
- To assess the relation between pharmacogenetic variation in CEP72 genotype and vinca alkaloid (vincristine; vinorelbine) disposition in children with rhabdomyosarcoma.
- To assess the relation between the pharmacogenetic variation in drug metabolizing enzymes and drug transporters, and the pharmacokinetics of vinca alkaloids, liposomal irinotecan, and cyclophosphamide in children with rhabdomyosarcoma.
- To assess the extent of inter-patient variability in the pharmacokinetics of vinca alkaloids, liposomal irinotecan, and cyclophosphamide in children with rhabdomyosarcoma, and explore possible associations between drug disposition and patient specific covariates (e.g., age, sex, race, weight).
- Estimate the cumulative incidence of local recurrence and overall 3-year event-free survival in patients with low-risk disease, intermediate-risk disease or high-risk disease treated with either no adjuvant radiation or minimal volume radiation and compare these outcomes with the outcomes achieved on RMS13.
Detailed description
This is a phase II study to determine safety and efficacy of combining liposomal irinotecan with vincristine alternating with VAC in intermediate-risk patients, liposomal irinotecan with temozolomide and vincristine alternating with VAC in high-risk patients and the chemotherapy combinations when given with concomitant radiation therapy in intermediate and high risk patients. The dose of liposomal irinotecan for intermediate and high risk patients will be 160/mg/m2 on Day 1 based on the results and recommended phase 2 dose of the Phase I trial ONITT trial. The primary objective is to assess event-free survival (EFS). The sample size is determined based on a 2-year EFS estimate for each risk group, with a total study duration of 4 years for enrollment and 2 years of follow-up per patient.
The study employs a single-arm adaptive Phase II design, with an estimated 46 patients in the intermediate-risk group and 34 patients in the high-risk group, ensuring 80% power and a 5% Type I error rate. The trial will conclude once the last enrolled patient has completed 2 years of follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low -risk | Experimental | Drug: Vincristine, Drug: Dactinomycin, Drug: Cyclophosphamide, Procedure: Surgical Resection, Procedure: Proton beam radiation or external beam radiation or brachytherapyThe participant will receive 12 weeks (4 cycles) of VAC chemotherapy (vincristine, dactinomycin and cyclophosphamide) followed by 12 weeks (4 cycles) of VA chemotherapy (vincristine, dactinomycin). Each cycle of VAC/VA chemotherapy will last for 3 weeks, for a total of 12 weeks (VAC or VA will be given in Week 1 of each cycle and vincristine will be given Weeks 2 and 3). At week 12, the participant will have scans and tests to reevaluate your tumor's response to the treatment. After surgery and radiation, the participant will receive an additional 12 weeks (4 cycles) of the same chemotherapy without cyclophosphamide. Vincristine and dactinomycin, also called "VA". After 4 cycles of VA, The investigator will re-evaluate the tumor again at week 24 and the patient will not get any more chemotherapy, but will be closely watched for any signs of tumor recurrence. |
| Intermediate-risk | Experimental | Drug: Vincristine, Drug: Dactinomycin, Drug: Cyclophosphamide, Procedure: Surgical Resection, Procedure: Proton beam radiation or external beam radiation or brachytherapy, Drug: Liposomal irinotecan, Drug: Vinorelbine, Drug: Filgrastim, peg-filgrastimThe purpose of this part of the study is to find out if adding a drug called liposomal irinotecan (also called Onivyde) to standard chemotherapy/radiation/surgery will result in better treatment outcomes for patients with intermediate and high risk rhabdomyosarcoma. The investigators also want to find the best radiation dose to give for intermediate and high risk patients who have large tumors (> 5 cm). The patient will receive 42 weeks of VAC chemotherapy (vincristine, actinomycin D/dactinomycin and cyclophosphamide) alternating with VLI chemotherapy (vincristine/liposomal irinotecan). The participant will also have surgery to remove the tumor and radiation therapy during this time. After this therapy is completed you will get an additional 6 months of maintenance chemotherapy with vinorelbine and oral (by mouth) cyclophosphamide. |
| High-risk | Experimental | Drug: Vincristine, Drug: Dactinomycin, Drug: Cyclophosphamide, Procedure: Surgical Resection, Procedure: Proton beam radiation or external beam radiation or brachytherapy, Drug: Liposomal irinotecan, Drug: Vinorelbine, Drug: Temozolomide, Drug: Filgrastim, peg-filgrastimThe purpose of this part of the study is to find out if adding a drug called liposomal irinotecan (also called Onivyde) to standard chemotherapy/radiation/surgery will result in better treatment outcomes for patients with high risk rhabdomyosarcoma. The investigator also want to find the best radiation dose to give for high risk patients who have large tumors (> 5 cm). The patient will receive 42 weeks of VAC chemotherapy (vincristine, actinomycin D/dactinomycin and cyclophosphamide) alternating with VLIT chemotherapy (vincristine/liposomal irinotecan/temozolomide). Also having surgery to remove the participants tumor and radiation therapy during this time. After this therapy is completed the patient will get an additional 6 months of maintenance chemotherapy with vinorelbine and oral (by mouth) cyclophosphamide. |
Who may qualify
- Ages
- Up to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (40 listed)
- Newly diagnosed participants with the diagnosis of rhabdomyosarcoma (RMS) of any subtype. This includes embryonal rhabdomyosarcoma (fusion negative), alveolar rhabdomyosarcoma (fusion positive), as well as spindle cell and sclerosing
- Must have either low-, intermediate-risk or high-risk disease, defined as:
- Low-risk: TP53 and MYOD1 negative AND
- Intermediate-risk: MYOD1 and TP53 negative AND
- o Stage 2/3 Group III
Key exclusion criteria (6 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VincristineAlso: OncovinLow -risk Administer IV push over 1 minute (or infusion via minibag as per institutional standards) on Day 1 of Weeks 1,8, 15 (3) doses. The maximum dose is 2 mg for all participants. Intermediate-risk Administer IV, over 1 minute, 3 doses, weekly on day1 High-risk Administer by IV infusion over 1 minute, 3 doses, weekly on day 1,8,15 | Drug | High-risk, Intermediate-risk, Low -risk |
| DactinomycinAlso: (actinomycin-D)Low-risk Administer by slow IV push over 1-5 minutes on Day 1 of Weeks 1, (1) dose. The maximum dose is 2.5 mg for all participants. Intermediate-risk Administer by slow IV over 1-5 minutes., 1 doses weekly on day 1 High-risk Administer by slow IV over 1-5 minutes, day1 | Drug | High-risk, Intermediate-risk, Low -risk |
| CyclophosphamideAlso: Cytoxan®.Low-risk Administer by IV infusion over 30-60 minutes on Day 1, 91) dose, Mesna and hydration will be given with IV cyclophosphamide according to institutional standards. Intermediate-risk Administer by IV infusion over 30-60 minutes, 1 dose, day 1 High-risk Administer by IV infusion over 30-60 minutes, 1 dose, day1 | Drug | High-risk, Intermediate-risk, Low -risk |
| Surgical ResectionLow, Intermediate and High-risk | Procedure or surgery | High-risk, Intermediate-risk, Low -risk |
| Proton beam radiation or external beam radiation or brachytherapyLow, Intermediate and High-risk | Procedure or surgery | High-risk, Intermediate-risk, Low -risk |
| Liposomal irinotecanAlso: (Onivyde®)Intermediate and High-risk Administer by IV infusion over 90 minutes, 1 dose on day 1 Liposomal irinotecan should be premedicated with dexamethasone (or an equivalent corticosteroid) if not contraindicated. Premedication with diphenhydramine and an H2 receptor antagonist (i.e., famotidine) are also encouraged. | Drug | High-risk, Intermediate-risk |
| VinorelbineAlso: NavelbineIntermediate and High-risk Administer via slow IV push over 6-10 minutes (or infusion via minibag as per institutional standards) on Day 1 of Weeks 43-45, 47-49, 51-53, 55-57, 59-61, 63-65. | Drug | High-risk, Intermediate-risk |
| TemozolomideAlso: TemodarHigh-risk Administer PO (or by NG or G tube) 5 doses, on Days 1-5 When administering with liposomal irinotecan, administer temozolomide prior to liposomal irinotecan. Preferably, administer on an empty stomach (at least 1 hour before and 2 hours after food) to improve absorption. When using temozolomide capsules, round dose to the nearest 5 mg capsule. The capsule may be opened, and contents mixed with applesauce or apple juice. A compounded oral suspension is also available. If emesis occurs within 20 minutes of taking a dose of temozolomide, then the dose may be repeated once. | Drug | High-risk |
| Filgrastim, peg-filgrastimAlso: NeupogenLow, Intermediate and High-risk: Prophylactic myeloid growth factor support (Filgrastim or Pegfilgrastim) should be used after all VAC cycles for patients on the high-risk arm. Start myeloid growth factor support (for example, filgrastim 5 mcg/kg/dose SubQ daily until the ANC is ≥ 2000/μL after the expected nadir OR pegfilgrastim 0.1 mg/kg/dose [for patients < 45 kg] or 6 mg/dose [for patients ≥ 45 kg] SubQ x 1 dose) 24-48 hours after VAC cycles. Filgrastim may be continued without regard to VCR. Discontinue filgrastim at least 24 hours before the start of the next cycle. Prophylactic myeloid growth factor support should NOT be used after VLIT cycles or during maintenance chemotherapy. | Drug | High-risk, Intermediate-risk |
Primary outcome
Maximum tolerated doses (MTDs)
Time frame: 4 years
MTD is defined in the study as the highest treatment dose that would deliver desirable treatment effects without resulting in a target toxicity rate greater than 0.3. For each of three groups (intermediate-risk, high-risk, and intermediate-and-high-risk-with-early-radiation), we will employ the Bayesian optimal interval (BOIN) design to find the MTD.
Event-free survival (EFS)
Time frame: 2 years post, off therapy
We will estimate the 2-year event-free survival for intermediate-risk and high-risk patients, which is the estimated probability of a patient not having any events within the 2-year follow-up. If an event, including local failure, distant failure, death or loss to follow-up occurs for a patient within 2-year, we call it failure, otherwise call it response.
Local recurrence rate (LRR)
Time frame: 2 years
LRR is defined as a binary endpoint in the study. The local recurrence-free survival (LRFS) is defined as time from randomization to the earlier date of the first of local disease recurrence or death due to any cause. The distant failure will be considered to be the competing risk, patients for whom follow-up ended without clinical improvement will be censored. The goal of the local recurrence rate endpoint is to evaluate the 2-year LRR by comparing the administration of 59.4 GyRBE and 68 GyRBE for patients (pooled intermediate- and high-risk groups) with tumor size greater than or equal to 5cm meeting the eligibility criteria for randomization (no biliary tree or specific extremity cases). .
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alberto Pappo, MD principal investigator
St. Jude Children's Research Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vincristine, Dactinomycin and Cyclophosphamide in people with Rhabdomyosarcoma, run by St. Jude Children's Research Hospital at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 40 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alberto Pappo, MD ((901) 595-2322, alberto.pappo@stjude.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated doses (MTDs) (time frame: 4 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2026.