Education and Training

Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma

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.

Stanford is currently accepting patients for this trial.

Intervention(s):

  • 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

Eligibility


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.

   - 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.

      - 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.

   - 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).

   - 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)

   - 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.

Ages Eligible for Study

N/A - 21 Years

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Ariel Fry Demetria
afrydeme@stanford.edu
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