A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma


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Trial ID: NCT04994132


This phase III trial compares the safety and effect of adding vinorelbine to vincristine, dactinomycin, and cyclophosphamide (VAC) for the treatment of patients with high risk rhabdomyosarcoma (RMS). High risk refers to cancer that is likely to recur (come back) after treatment or spread to other parts of the body. This study will also examine if adding maintenance therapy after VAC therapy, with or without vinorelbine, will help get rid of the cancer and/or lower the chance that the cancer comes back. Vinorelbine and vincristine are in a class of medications called vinca alkaloids. They work by stopping cancer cells from growing and dividing and may kill them. Dactinomycin is a type of antibiotic that is only used in cancer chemotherapy. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Vinorelbine, vincristine, dactinomycin and cyclophosphamide are chemotherapy medications that work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may have the potential to eliminate rhabdomyosarcoma for a long time or for the rest of patient's life.

Official Title

A Randomized Phase 3 Trial of Vinorelbine, Dactinomycin, and Cyclophosphamide (VINO-AC) Plus Maintenance Chemotherapy With Vinorelbine and Oral Cyclophosphamide (VINO-CPO) vs Vincristine, Dactinomycin and Cyclophosphamide (VAC) Plus VINO-CPO Maintenance in Patients With High Risk Rhabdomyosarcoma (HR-RMS)

Stanford Investigator(s)


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

   - 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

   - 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

      - 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

   - 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


drug: Cyclophosphamide

biological: Dactinomycin

radiation: Radiation Therapy

drug: Vincristine Sulfate

drug: Vinorelbine Tartrate

procedure: Biospecimen Collection

procedure: Bone Marrow Aspiration

procedure: Bone Marrow Biopsy

procedure: Bone Scan

procedure: Computed Tomography

procedure: Magnetic Resonance Imaging

procedure: Positron Emission Tomography

procedure: X-Ray Imaging


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Chloe Anne Lontoc Ordona
650-724-4042 Primary +1 650-721-4074

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