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A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
Recruiting
I'm InterestedTrial ID: NCT04994132
Purpose
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)
Eligibility
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
Intervention(s):
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
Recruiting
I'm InterestedContact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
Chloe Anne Lontoc Ordona
650-724-4042 Primary +1 650-721-4074