IRB Study Number 24-037
Status Recruiting
Institute Taussig Cancer Institute
Description
1.1 Primary Objectives
1.1.1 To evaluate the failure free survival (FFS) of patients with very low-risk (VLR) rhabdomyosarcoma (RMS) (fusion negative (FN), Stage 1, Clinical Group (CG) I, MYOD1 wildtype (WT), TP53 (WT) when treated with 24 weeks of vincristine and dactinomycin (VA).
1.1.2 To evaluate the FFS of patients with low-risk (LR) RMS (FN, Stage 1 CG II, or Stage 2 CG I/II or CG III (orbit only), MYOD1 WT, TP53 WT) when treated with 12 weeks of vincristine, dactinomycin and cyclophosphamide (VAC) followed by 12 weeks of VA.
1.2 Secondary Objectives
1.2.1 To evaluate the overall survival (OS) of patients with VLR RMS treated with 24 weeks of VA.
1.2.2 To evaluate the OS of patients with LR RMS treated with 12 weeks of VAC followed by 12 weeks of VA.
1.2.3 To demonstrate the feasibility of central molecular risk stratification of patients with newly diagnosed RMS in the context of a prospective clinical trial.
Inclusion Criteria
3.2.1 Enrollment on APEC14B1 and Consent to Molecular Characterization All patients must be enrolled on APEC14B1 and consented to the Molecular Characterization Initiative (Part A) prior to enrollment and treatment on ARST2032. See Section 3.1.4 for timing details.
3.2.2 Age
Patients must be ≤ 21 years at the time of enrollment.
3.2.3 Diagnosis
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 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).23 Enrollment in APEC14B1 is required for all patients.
3.2.3.1 All patients will be evaluated for Stage and Clinical Group (see Appendices III and IV for Stage and Grouping information). 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.
a. Patients will be eligible for the very low-risk stratum (Regimen VA) if they have Stage 1, CG I disease.
b. 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.
3.2.3.2 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.
3.2.3.3 Extremity Tumors: Regional lymph node sampling is required for histologic evaluation in patients with extremity tumors (see Appendix III and Appendix IV).
3.2.3.4 Clinically or radiographically enlarged nodes must be sampled for histologic evaluation (see Appendix III and Appendix IV).
3.2.4 Performance Level
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. See https://members.childrensoncologygroup.org/prot/reference\_materials.asp under Standard Sections for Protocols.
3.2.5 Organ Function Requirements
3.2.5.1 Adequate bone marrow function defined as:
Peripheral absolute neutrophil count (ANC) ≥ 750/μL
Platelet count ≥ 75,000/μL (transfusion independent)
3.2.5.2 Adequate renal function defined as:
Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or
A serum creatinine based on age/gender as follows: (See protocol)
3.2.5.3 Adequate liver function defined as:
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and
SGPT (ALT) ≤ 135 U/L*
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
Exclusion Criteria
3.2.6 Prior Therapy
3.2.6.1 Patients who have received prior chemotherapy and/or radiation therapy for cancer prior to enrollment. Surgical resection alone of previous cancer(s) is permitted.
3.2.6.2 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.
3.2.6.3 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. Please see Section 4.1.3 for the concomitant therapy restrictions for patients during treatment.
3.2.7 Patients unable to undergo radiation therapy, if necessary, as specified in the protocol.
3.2.8 Evidence of uncontrolled infection
3.2.9 Pregnancy and Breastfeeding,
3.2.9.1 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.
3.2.9.2 Lactating females who plan to breastfeed their infants.
3.2.9.3 Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
3.2.10 Regulatory Requirements
3.2.10.1 All patients and/or their parents or legal guardians must sign a written informed consent.
3.2.10.2 All institutional, FDA, and NCI requirements for human studies must be met.
