Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma
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| ClinicalTrials.gov Identifier: NCT05304585 |
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Recruitment Status :
Recruiting
First Posted : March 31, 2022
Last Update Posted : November 21, 2023
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Sponsor:
Children's Oncology Group
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
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Brief Summary:
Rhabdomyosarcoma is a type of cancer that occurs in the soft tissues in the body. This phase III trial aims to maintain excellent outcomes in patients with very low risk rhabdomyosarcoma (VLR-RMS) while decreasing the burden of therapy using treatment with 24 weeks of vincristine and dactinomycin (VA) and examines the use of centralized molecular risk stratification in the treatment of rhabdomyosarcoma. Another aim of the study it to find out how well patients with low risk rhabdomyosarcoma (LR-RMS) respond to standard chemotherapy when patients with VLR-RMS and patients who have rhabdomyosarcoma with DNA mutations get separate treatment. Finally, this study examines the effect of therapy intensification in patients who have RMS cancer with DNA mutations to see if their outcomes can be improved.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Embryonal Rhabdomyosarcoma Fusion-Negative Alveolar Rhabdomyosarcoma Spindle Cell/Sclerosing Rhabdomyosarcoma | Procedure: Biopsy Procedure: Bone Scan Procedure: Computed Tomography Drug: Cyclophosphamide Biological: Dactinomycin Procedure: Magnetic Resonance Elastography Procedure: Positron Emission Tomography Radiation: Radiation Therapy Drug: Vincristine | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 205 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Prospective Phase 3 Study of Patients With Newly Diagnosed Very Low-Risk and Low-Risk Fusion Negative Rhabdomyosarcoma |
| Actual Study Start Date : | August 4, 2022 |
| Estimated Primary Completion Date : | December 31, 2030 |
| Estimated Study Completion Date : | December 31, 2030 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Regimen M (positive mutation)
Patients receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 2-4, 7-8, and 11-12 and dactinomycin IV over 1-5 minutes or 10-15 minutes on day 1 of cycles 2-5 and 8-14. Patients also receive cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 12-13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo radiation therapy at cycle 5. Patients undergo CT scan, MRI, bone scan, PET scan and tumor biopsy throughout the study.
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Procedure: Biopsy
Undergo tumor biopsy
Other Names:
Procedure: Bone Scan Undergo bone scan
Other Name: Bone Scintigraphy Procedure: Computed Tomography Undergo CT scan
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Biological: Dactinomycin Given IV
Other Names:
Procedure: Magnetic Resonance Elastography Undergo MRI
Other Name: MRE Procedure: Positron Emission Tomography Undergo PET scan
Other Names:
Radiation: Radiation Therapy Undergo radiation
Other Names:
Drug: Vincristine Given IV
Other Names:
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Experimental: Regimen VA (VLR RMS)
Patients with VLR RMS receive vincristine intravenously (IV) on day 1 of each cycle and days 8 and 15 of cycles 1, 3, 5, and 7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Patients undergo CT scan, MRI, bone scan, PET scan and tumor biopsy throughout the study.
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Procedure: Biopsy
Undergo tumor biopsy
Other Names:
Procedure: Bone Scan Undergo bone scan
Other Name: Bone Scintigraphy Biological: Dactinomycin Given IV
Other Names:
Procedure: Magnetic Resonance Elastography Undergo MRI
Other Name: MRE Procedure: Positron Emission Tomography Undergo PET scan
Other Names:
Drug: Vincristine Given IV
Other Names:
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Experimental: Regimen VAC/VA (VL RMS)
Patients with LR RMS receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 1-3. Patients also receive dactinomycin IV over 1-5 minutes or 10-15 minutes and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 5-7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Radiation therapy (if needed) will be administered at cycle 5.Patients undergo CT scan, MRI, bone scan, PET scan and tumor biopsy throughout the study.
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Procedure: Biopsy
Undergo tumor biopsy
Other Names:
Procedure: Bone Scan Undergo bone scan
Other Name: Bone Scintigraphy Procedure: Computed Tomography Undergo CT scan
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Biological: Dactinomycin Given IV
Other Names:
Procedure: Magnetic Resonance Elastography Undergo MRI
Other Name: MRE Procedure: Positron Emission Tomography Undergo PET scan
Other Names:
Drug: Vincristine Given IV
Other Names:
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Primary Outcome Measures :
- Failure free survival (FFS) for very low risk patients [ Time Frame: From study enrollment to disease progression, recurrence, or death as a first event, assessed up to 3 years ]The Kaplan-Meier method will be used to estimate 3-year FFS along with 80% log-minus-log transformed confidence limits for very low risk (VLR) patients.
- Failure free survival (FFS) for low risk patients [ Time Frame: From study enrollment to disease progression, recurrence, or death as a first event, assessed up to 3 years ]The Kaplan-Meier method will be used to estimate 3 year FFS along with 80% log-minus-log transformed confidence limits for low risk (LR) patients.
Secondary Outcome Measures :
- Overall survival (OS) for very low risk patients [ Time Frame: From study entry to death of any cause, assessed up to 5 years ]Log-rank test will be used to compare the OS of patients with VLR rhabdomyosarcoma (RMS) treated with 24 weeks of vincristine, dactinomycin (VA) to the VLR RMS patients from ARST0331 and D9602 with the same inclusion criteria.
- Overall survival (OS) for low risk patients [ Time Frame: From study entry to death of any cause, assessed up to 5 years ]Log-rank test will be used to compare the OS from LR RMS patients to LR RMS patients from ARST0331 and D9602 with the same inclusion criteria.
- Feasibility of central molecular risk stratification of patients assessed by the percentage of patients who have molecular testing results returned by 6 weeks [ Time Frame: Up to 24 weeks ]If the percentage of patients who have molecular testing results returned by 6 weeks is >= 80% then the central molecular risk stratification is considered feasible.
Other Outcome Measures:
- Methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma [ Time Frame: Up to 5 years ]Summary statistics will be used to describe the methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma. Correlation between methylation patterns and clinical presentation, histology, and genetics will be evaluated.
Information from the National Library of Medicine
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| Ages Eligible for Study: | up to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- All patients must be enrolled on APEC14B1 (NCT02402244) and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032 (this trial).
- Patients must be =< 21 years at the time of enrollment.
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Patients must have newly diagnosed embryonal rhabdomyosarcoma (ERMS), spindle cell/sclerosing RMS, or FOXO1 fusion negative alveolar rhabdomyosarcoma (ARMS) (institutional FOXO1 fusion results are acceptable). RMS types included under 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 2020 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). Enrollment in APEC14B1 is required for all patients.
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All patients will be evaluated for stage and clinical group. Note that clinical group designation assigned at the time of enrollment on study remains unchanged regardless of any second-look operation that may be performed.
- Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease.
- Patients will be eligible for the low-risk stratum (Regimen VAC/VA) if they have Stage 1, CG II disease, Stage 2, CG I or II disease, or Stage 1, CG III (orbit only) disease.
- Paratesticular Tumors: Staging ipsilateral retroperitoneal lymph node sampling (SIRLNS) is required for all patients >= 10 years of age with paratesticular tumors who do not have gross nodal involvement on imaging.
- Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors.
- Clinically or radiographically enlarged nodes must be sampled for histologic evaluation.
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- Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for patients > 16 years of age) performance status score of >= 50. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score.
- Peripheral absolute neutrophil count (ANC) >= 750/uL (within 7 days prior to enrollment).
- Platelet count >= 75,000/uL (transfusion independent) (within 7 days prior to enrollment).
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Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine (within 7 days prior to enrollment) based on age/gender as follows:
- Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male) : 0.4 (female)
- Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male) : 0.5 (female)
- Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) : 0.6 (female)
- Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) : 0.8 (female)
- Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) : 1 (female)
- Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) : 1.2 (female)
- Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) : 1.4 (female)
- Age >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) : 1.4 (female)
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Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and
- If there is evidence of biliary obstruction by the tumor, then the total bilirubin must be < 3 x ULN for age.
- Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L.
- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment).
- 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 received prior chemotherapy and/or radiation therapy for cancer prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.
- Patients who have received chemotherapy or radiation for non-malignant conditions (e.g., autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy.
- Vincristine is sensitive substrate of the CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment.
- Patients unable to undergo radiation therapy, if necessary, as specified in the protocol.
- Evidence of uncontrolled infection.
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- Lactating females who plan to breastfeed their infants.
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05304585
Locations
Show 141 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Josephine H Haduong | Children's Oncology Group |
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT05304585 |
| Other Study ID Numbers: |
ARST2032 NCI-2022-01012 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ARST2032 ( Other Identifier: Children's Oncology Group ) ARST2032 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) |
| First Posted: | March 31, 2022 Key Record Dates |
| Last Update Posted: | November 21, 2023 |
| Last Verified: | November 2023 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Additional relevant MeSH terms:
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Rhabdomyosarcoma Rhabdomyosarcoma, Alveolar Rhabdomyosarcoma, Embryonal Myosarcoma Neoplasms, Muscle Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Sarcoma Dactinomycin Cactinomycin Cyclophosphamide Vincristine Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Protein Synthesis Inhibitors |