Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Rare Diseases

Sarcoma

Respiratory Aspiration

Rhabdomyosarcoma

Myosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Irinotecan

Etoposide

Vinorelbine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Vincristine

Ifosfamide

Dactinomycin

Etoposide phosphate

Isophosphamide mustard

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide

Participants will receive conventional doses of Vincristine/Actinomycin D/Cyclophosphamide (VAC) until complete response (CR) for 12-42 weeks and then switch to up to 2 years of vinorelbine/oral cyclophoshamide

Therapy with VAC that starts and stops based on response, adaptive timing of therapy, with a prolonged time to progression rather than complete remission goal

Participants will receive a chemotherapy combination based on published trials. An example would be 42 weeks of VAC but may also include irinotecan, doxorubicin, ifosfamide, etoposide.

IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg

IV over 60 minutes with dosing ranging from 220mg to 1200mg

IV push over 6-10 minutes with dosing ranging from 4mg-25mg

Actinomycin D should not be given with radiation. Will be administered through IV over 3-5 minutes with dosing ranging from 0.025mg-0.045mg

Actinomycin D

Based on Body Surface Area (BSA) round to nearest 25mg

Cyclophosphamide Pill

Jessica Crimella, BSN, RN

Stella Valavanis, MPH

Jennifer Madison

Bridget Tate

Elizabeth Alva, MD

Sarah Miller

Emily Blauel-Bocko, MD

Robin Arens

Michael Scott Isakoff, MD

Ashley P Bayne

Joanne P Lagmay, MD

Eva Pavicic

Aditi Dhir, MD

Brittani Froug

Emily Riffle

Jonathan Metts, MD

Jessica R Crimella, BSN, RN

Rebecca Zylber

Alice Lee, MD

Stephanie Guilford

Ajay Gupta, MD

Juanita Cuffee

Patrick Thompson, MD

Devika Srivastava

Abigail Moore

Javier Oesterheld, MD

Lars Wagner, MD

Melissa Serna

Matteo Trucco, MD

Hannah Johns

Bhuvana Setty, MD

Joshua Blatner

Scott Borinstein, MD

Nupur Goel

Patrick Leavey, MD

Latasha Williams

Jonathan Gill, MD

Jessica Jensen

Michelle Grant

Matthew Dietz, MD

This clinical trial will evaluate 4 different strategies of chemotherapy schedules in newly diagnosed participants with metastatic Fusion Positive (alveolar) Rhabdomyosarcoma. The participant and their physician will choose from: Arm A) a first strike therapy, Arm B) a first strike-second strike (maintenance) therapy, Arm C) an adaptively timed therapy, and Arm D) conventional chemotherapy.

Evolutionary Therapy for Rhabdomyosarcoma

Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma

Participants who choose the first strike treatment will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) any recurrence (local or regional, or distant) and (2) death due to any cause.

Participants who choose the second strike treatment will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) any recurrence (local or regional, or distant) and (2) death due to any cause

Participants who choose the adaptive therapy will have event free survival assessed at 3 years after initiating treatment. Event free survival is defined as time from treatment initiation to event which includes (1) progression that does not respond to additional VAC dosing and (2) death due to any cause

The time to event endpoint of overall survival is defined as the duration of time from diagnosis to death or last follow-up, where event would be death from any cause

Number of participants with treatment-related adverse events of a certain grade or higher and hematological/biochemical toxicities based on laboratory measurements as assessed by CTCAE v5.0

National Pediatric Cancer Foundation

H. Lee Moffitt Cancer Center and Research Institute

Analgesics

Central Nervous System Depressants

Amino Acids

Antibodies

Morphine

Temozolomide

Immunoglobulins

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Mechlorethamine

Nitrogen Mustard Compounds

Vinca Alkaloids

Topoisomerase I Inhibitors

Tyrosine

Irinotecan: an i.v. infusion over 1 hour on days 8,9,10,11 and 12 . For the phase 1b registration, starting dose of 20 mg/m2.

Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 as an As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on days 1 and 8 on cycles 3-9.

Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.

Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on day 1 on cycles 3-9.

Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1. Doxorubicin: 30 mg/m2 as an i.v infusion over 1 hour on days 1 and 2 on cycles 1-4

Irinotecan: an i.v. infusion over 1 hour on days 8,9,10,11 and 12 . Phase 2 recommended dose as determined by IRIVA dose finding arm Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on days 1 and 8 on cycles 3-9.

Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.

Ifosfamide: 3g/m2 as an i.v. infusion over 3 hours on days 1 and 2 Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg). Administered days 1,8,15 on cycles 1-2 and on day 1 on cycles 3-9.

Actinomycin: 1.5 mg/m2 as an i.v. bolus injection (maximum dose 2mg) on day 1.

To be given either 41.4 Gy or 50.4 Gy prior to surgery

To be given either 41.4 Gy or 50.4 Gy following surgery

Radiotherapy to the primary tumour and involved regional lymph nodes only

Radiotherapy given to all metastatic sites

Vinorelbine: 25 mg/m2 i.v. or 60 mg/m2 orally on days 1,8 and 15 Cyclophosphamide 25 mg/m2 orally daily for 28 days

To stop treatment at the point of randomisation

Vinorelbine: 25 mg/m2 i.v. on days 1,8 and 15 Cyclophosphamide 25 mg/m2 orally daily for 28 days

Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg) on days 1 and 8 Irinotecan: 50 mg/m2 as an i.v. infusion over 1 hour on days 1-5 Temozolomide: 125 mg/m2 (Escalate to 150mg/m2/day in Cycle 2 if no toxicity \> grade 3) as an oral tablets prior to vincristine and irinotecan on days 1-5

Vincristine: 1.5 mg/m2 As per local practice: recommended as a short infusion (maximum dose 2mg) on days 1 and 8 Irinotecan: 50 mg/m2 as an i.v. infusion over 1 hour on days 1-5 Regorafenib: Children between 6 and 24 months = 65 mg/m2, children less than 12 and/or less than 40kg dose = 82 mg/m2 Maximum 120 mg, Fixed dose of 120 mg for patients over 12 years of age AND ≥ 40 kg, as an oral tablets on days 8 to 21.

Antineoplastic agent that is a polypeptide antibiotic

An anthracycline topoisomerase inhibitor isolated from streptpmyces peucetius var. casesius

chemotherapeutic agent chemically related to the nitrogen mustards and is a synthetic analog of cyclophosphamide

vinca alkaloid with a role as an antineoplastic agent

Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent

radiotherapy

Oral multi-kinase inhibitor that targets a broad range of angiogenic, stromal and oncogenic kinases, including vascular endothelial growth factor receptors (VEFGR) 1, 2 and 3, tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 (TIE2), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR), c-KIT, RET, RAF-1 and BRAF (wild-type and V600E mutant).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Evolutionary Therapy for Rhabdomyosarcoma	NCT04388839	Rhabdomyosarcom...	Vincristine Cyclophosphamid... Vinorelbine Actinomycin D Cyclophosphamid...	-	H. Lee Moffitt Cancer Center and Research Institute
FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma	NCT04625907	Rhabdomyosarcom...	Irinotecan Actinomycin D Doxorubicin Ifosfamide Vincristine Vinorelbine Cyclophosphamid... Temozolomide radiotherapy Regorafenib	-	University of Birmingham
Study of Paclitaxel Plus Cisplatin as the First-line Chemotherapy in High Risk Gestational Trophoblastic Tumor	NCT02639650	Gestational Tro...	Etoposide actinomycin D methotrexate vincristine cyclophosphamid... Paclitaxel Cisplatin Carboplatin	- 60 Years	Women's Hospital School Of Medicine Zhejiang University

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