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

S
Sandeep Batra, MD

Primary Investigator

Enrolling By Invitation
50 years or below
All
Phase 3
118 participants needed
1 Location

Brief description of study

What is the purpose of this study?
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 riskhabdomyosarcoma (RMS). High risk refers to cancer that is likely to recur (come back) afterd to other parts of the body. This study will also examine if addingherapy after VAC therapy, with or without vinorelbine, will help get rid of thed/or lower the chance that the cancer comes back. Vinorelbine and vincristine are indications 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) andy kill cancer cells. Cyclophosphamide is in a class of medications called alkylatinggents. 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 arehemotherapy medications that work in different ways to stop the growth of cancer cells,her by killing the cells, by stopping them from dividing, or by stopping them fromding. This trial may have the potential to eliminate rhabdomyosarcoma for a long time orhe rest of patient's life.
 
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic. 
 
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

What will happen during the study?
  • Patients are randomized to 1 of 2 arms.
  • ARM A: Patients receive vincristine sulfate intravenously (IV) on days 1, 8 and 15 of cycles 1-4, 7, 8, 11, and 12, and day 1 of cycles 5, 6, 9, 10, 13, and 14. Patients also receive dactinomycin IV over 1-15 minutes or IV push (IVP) over 1-5 minutes on day 1 of cycles 1-5, 8-10, and 11-14, and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatmentvery 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on weeks 13 and 40.
  • ARM B: Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1 and 8, vincristine sulfate IV on day 15, dactinomycin IV over 1-15 minutes or IVP over 1-5 minutesday 1 of cycles 1-5 and 8-14, and cyclophosphamide IV over 60 minutes on day 1. Treatmentvery 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on weeks 13 and 40.
  • MAINTENANCE: All patients receive vinorelbine tartrate IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide orally (PO) on days 1-28. Treatment repeats every 28 days for up to 6ycles in the absence of disease progression or unacceptable toxicity.
  • Patients in both arms undergo computed tomography (CT), magnetic resonance imaging (MRI),graphy (PET), x-ray imaging, and/or bone scan, as well as blood samplehroughout the trial. Patients may also undergo bone marrow aspiration and/or biopsy as clinically indicated
  • After completion of study treatment, patients are followed up every 3 months for year 1,very 4 months for years 2-3, and every 6 months for years 4-5.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Riley, Alveolar Rhabdomyosarcoma, Botryoid-Type Embryonal Rhabdomyosarcoma, Embryonal Rhabdomyosarcoma, Metastatic Embryonal Rhabdomyosarcoma, Metastatic Rhabdomyosarcoma, Solid Alveolar Rhabdomyosarcoma, Spindle Cell Rhabdomyosarcoma, Spindle Cell/Sclerosing Rhabdomyosarcoma
  • Age: 50 years or below
  • Gender: All

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, basedupon institutional histopathologic classification are eligible to enroll on the studybased upon stage, group, and age, as below. FOXO1 fusion status must be determined byweek 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) includehose classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) asRMS (classic, spindle cell, and botryoid variants), which are reclassified in the2020 World Health Organization (WHO) Classification as ERMS (classic, dense andbotryoid variants) and spindle cell/sclerosing RMS (encompassing the historicaldle cell ERMS variant and the newly recognized sclerosing RMS variant).Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as inhe 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 therapybased 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 marrowvolvement on H&E, patients with bone marrow involvement detected ONLY by flowytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence inu hybridization (FISH), or immunohistochemistry will NOT be considered to havebone marrow involvement for the purposes of this study
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70L/min/1.73 m^2 or a serum creatinine based on age/gender as follows (must bed 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 mustbe < 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 treatedwith chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) iswed
  • 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 aregible, provided they are consented to ARST2031 prior to administration ofdiation

    • Note: Patients who have received or are receiving chemotherapy or radiation for

      non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients mustdiscontinue chemotherapy for non-malignant conditions prior to starting protocolherapy

  • Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients

    must not have received drugs that are moderate to strong CYP3A4 inhibitors andducers within 7 days prior to study enrollment
  • Female patients who are pregnant since fetal toxicities and teratogenic effects havebeen noted for several of the study drugs. A pregnancy test is required for femalehildbearing potential
  • Lactating females who plan to breastfeed their infants
  • Sexually active patients of reproductive potential who have not agreed to use anve contraceptive method for the duration of their study participation

Updated on 13 Dec 2024. Study ID: ARST2031, PHO-COG-ARST2031, 13353
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