High-Risk Rhabdomyosarcoma: VINO-AC

What is the Purpose of this Study?

This study focuses on patients who have been diagnosed with high-risk rhabdomyosarcoma (RMS). RMS is a type of cancer that occurs in the soft tissues of the body (like the muscles). RMS is considered high-risk when it has spread to other areas of the body. The purpose of the study is to evaluate whether an experimental drug called vinorelbine can be given safely in combination with the standard chemotherapy drugs vincristine, dactinomycin, and cyclophosphamide (together called VINO-AC with vincristine). Vinorelbine is in the same class of drugs as vincristine and stops cancer cells from dividing. Researchers also aim to determine whether they can improve outcomes for patients with high-risk RMS by extending the traditional treatment to include a treatment phase called maintenance therapy. All participants will receive maintenance therapy, during which they will receive vinorelbine and cyclophosphamide.

Eligibility

Patients must be =< 50 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. FOXO1 fusion status must be determined by week 4 (day 28) of therapy. RMS types included under embryonal RMS (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). Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in the ICR and includes classic and solid variants

Inclusion Criteria:

Patients must be =< 50 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. FOXO1 fusion status must be determined by week 4 (day 28) of therapy. RMS types included under embryonal RMS (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). Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in the ICR and includes classic and solid variants
ERMS
Stage 4, group IV, >= 10 years of age
ARMS
Stage 4, group IV Patients will be eligible to remain on protocol therapy based upon stage, group, and age
Bone marrow metastatic disease is based on morphologic evidence of RMS based on hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study
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 (must be performed within 7 days prior to enrollment):
Age; Maximum serum creatinine (mg/dL)
1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
>= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
If there is evidence of biliary obstruction by tumor, then total bilirubin must be < 3 x 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 with evidence of uncontrolled infection are not eligible
RMS that is considered a second malignancy and previous cancer(s) that were treated with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is allowed
Patients with central nervous system involvement of RMS as defined below:
Malignant cells detected in cerebrospinal fluid
Intra-parenchymal brain metastasis separate and distinct from primary tumor (i.e., direct extension from parameningeal primary tumors is allowed).
Diffuse leptomeningeal disease
Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy for RMS prior to enrollment.
Note: the following exception:
Patients requiring emergency radiation therapy for RMS. These patients are eligible, provided they are consented to ARST2031 prior to administration of radiation
Note: Patients who have received or are receiving 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 and vinorelbine are sensitive substrates of 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
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

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Where can I participate?

Cedars-Sinai Cancer at SOCC

More about this Clinical Trial

What is the full name of this clinical trial?

ARST2031: A Randomized Phase 3 Trial of Vinorelbine, Dactinomycin, and Cyclophosphamide Plus Maintenance Chemotherapy with Vinorelbine and Oral Cyclophosphamide vs Vincristine, Dactinomycin and Cyclophosphamide plus VINO-CPO Maintenance in Patients with High Risk Rhabdomyosarcoma *^

Study Details

Disease Type/Condition

Soft Tissue

Principal Investigator

Mascarenhas, Leo

Co-Investigators

Behrooz Hakimian, Fataneh Majlessipour, Nicole Baca

Age Group

Both

Phase

III

IRB Number

STUDY00002684

ClinicalTrials.gov ID

NCT04994132

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org