Evolutionary Therapy for Rhabdomyosarcoma
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04388839 |
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Recruitment Status :
Recruiting
First Posted : May 14, 2020
Last Update Posted : November 21, 2022
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Sponsor:
H. Lee Moffitt Cancer Center and Research Institute
Collaborator:
National Pediatric Cancer Foundation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Rhabdomyosarcoma | Drug: Vincristine Drug: Cyclophosphamide Drug: Vinorelbine Drug: Actinomycin D Drug: Cyclophosphamide Pill | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 28 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Evolutionary Inspired Therapy for Newly Diagnosed, Metastatic, Fusion Positive Rhabdomyosarcoma |
| Actual Study Start Date : | September 27, 2020 |
| Estimated Primary Completion Date : | December 2026 |
| Estimated Study Completion Date : | December 2027 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Dactinomycin
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A - First Strike
Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide
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Drug: Cyclophosphamide
IV over 60 minutes with dosing ranging from 220mg to 1200mg Drug: Vinorelbine IV push over 6-10 minutes with dosing ranging from 4mg-25mg
Other Name: Navelbine Drug: Actinomycin D 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
Other Name: Cosmegen |
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Experimental: Arm B - Second Strike - Maintenance
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
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Drug: Vincristine
IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg Drug: Cyclophosphamide IV over 60 minutes with dosing ranging from 220mg to 1200mg Drug: Vinorelbine IV push over 6-10 minutes with dosing ranging from 4mg-25mg
Other Name: Navelbine Drug: Actinomycin D 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
Other Name: Cosmegen Drug: Cyclophosphamide Pill Based on Body Surface Area (BSA) round to nearest 25mg |
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Experimental: Arm C - Adaptive Therapy
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
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Drug: Vincristine
IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg Drug: Cyclophosphamide IV over 60 minutes with dosing ranging from 220mg to 1200mg Drug: Actinomycin D 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
Other Name: Cosmegen |
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Active Comparator: Arm - D Conventional Therapy
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.
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Drug: Vincristine
IV push over 1 minute with dosing ranging from 0.24mg up to 1.5mg Drug: Cyclophosphamide IV over 60 minutes with dosing ranging from 220mg to 1200mg Drug: Actinomycin D 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
Other Name: Cosmegen |
Primary Outcome Measures :
- First Strike Event Free Survival [ Time Frame: Baseline to 3 years ]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.
- Second Strike Event Free Survival [ Time Frame: Baseline to 3 years ]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
- Adaptive Therapy Event Free Survival [ Time Frame: Baseline to 3 years ]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
Secondary Outcome Measures :
- Overall Survival [ Time Frame: 5 years ]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
- Treatment-related adverse events of a certain grade or higher [ Time Frame: Baseline to 5 years ]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
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Participants must have a new histologic diagnosis of rhabdomyosarcoma
- Participants must have FISH, PCR or other molecular confirmation of PAX/FOXO1 fusion per institutional standards
- Participants must have sufficient tissue (up to 10 unstained FFPE) for correlative testing
- All participants must have distant metastatic disease; either biopsy positive or PET avid extranodal or distant nodal lesions determined by the investigator to be metastatic disease. Patients with a single distant metastatic site that has been excised prior to study entry are eligible
- No prior systemic chemotherapy
- Participants enrolled to Arm B, maintenance, must be able to take oral cyclophosphamide. Note: enteral administration of cyclophosphamide is allowable.
- Males and females of reproductive potential may not participate unless they have agreed to the use of, at minimum, two methods of contraception during and after treatment or abstinence.
- Women of childbearing potential should adhere to contraception for a period of 4 months after completion of systematic chemotherapy administration
- Men who are sexually active with women of child bearing potential should adhere to contraception for a period of 4 months after completion of systematic chemotherapy administration
- All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document.
Exclusion Criteria:
- Participants with regional lymph nodes as the only site of disease are not eligible. Distant nodal sites alone are eligible
- Participants who are receiving any other investigational agents for rhabdomyosarcoma are ineligible
- Participants must not be receiving any additional medicines being given for the specific purpose of treating cancer. Alternative medications including, but not limited to cannabis based products would not be a reason for exclusion
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Participants are ineligible if they have uncontrolled intercurrent illness including, but not limited to:
- ongoing or active infection not expected to resolve with current antibiotic plan
- cardiac arrhythmia
- psychiatric illness/social situations that would limit compliance with study requirements
- Patients who are pregnant or breastfeeding are not eligible because there is no available information regarding human fetal or teratogenic toxicities. Females of childbearing potential must have a negative serum or urine pregnancy test within 24 hours of starting protocol therapy.
- Participants who are considered unable to comply with the safety monitoring requirements of the study are not eligible
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04388839
Contacts
| Contact: Jessica Crimella, BSN, RN | 813-745-6250 | Jessica.Crimella@moffitt.org | |
| Contact: Stella Valavanis, MPH | 813-745-6986 | Stella.Valavanis@moffitt.org |
Locations
Show 17 study locations
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
National Pediatric Cancer Foundation
Investigators
| Principal Investigator: | Damon Reed, MD | Moffitt Cancer Center |
Additional Information:
| Responsible Party: | H. Lee Moffitt Cancer Center and Research Institute |
| ClinicalTrials.gov Identifier: | NCT04388839 |
| Other Study ID Numbers: |
MCC-20339 |
| First Posted: | May 14, 2020 Key Record Dates |
| Last Update Posted: | November 21, 2022 |
| Last Verified: | November 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
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Soft Tissue Cancer Skeletal Muscle Tissue Cancer Sarcoma |
Additional relevant MeSH terms:
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Rhabdomyosarcoma Myosarcoma Neoplasms, Muscle Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Sarcoma Dactinomycin Cyclophosphamide Vincristine Vinorelbine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |
Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Protein Synthesis Inhibitors Enzyme Inhibitors Nucleic Acid Synthesis Inhibitors |