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FaR-RMS: An Overarching Study for Children and Adults With Frontline and Relapsed RhabdoMyoSarcoma
FaR-RMS is an over-arching study for children and adults with newly diagnosed and relapsed rhabdomyosarcoma (RMS).
Study details:
FaR-RMS is an over-arching study for children and adults with newly diagnosed and relapsed rhabdomyosarcoma (RMS). It is a multi-arm, multi-stage format, involving several different trial questions. FaR-RMS is intended to be a rolling programme of research with new treatment arms being introduced dependant on emerging data and innovation.
This study has multiple aims. It aims to evaluate the impact of new agent regimens in both newly diagnosed and relapsed RMS; whether changing the duration of maintenance therapy affects outcome; and whether changes to dose, extent (in metastatic disease) and timing of radiotherapy improve outcome and quality of life. In addition the study will evaluate risk stratification through the use of PAX-FOXO1 fusion gene status instead of histological subtyping and explore the use of FDG PET-CT response assessment as a prognostic biomarker for outcome following induction chemotherapy.
Newly diagnosed patients should, where possible, be entered into the FaR-RMS study at the time of first diagnosis prior to receiving any chemotherapy. However, patients can enter at the point of radiotherapy or maintenance, and those with relapsed disease can enter the study even if not previously entered at initial diagnosis. Patients may be entered into more than one randomisation/registration, dependant on patient risk group and disease status.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 0 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2020-09-17
Primary completion: 2030-06-01
Study completion finish: 2030-06-01
Study type
TREATMENT
Phase
PHASE1
PHASE2
Trial ID
NCT04625907
Intervention or treatment
DRUG: Irinotecan
DRUG: Actinomycin D
DRUG: Doxorubicin
DRUG: Ifosfamide
DRUG: Vincristine
DRUG: Vinorelbine
DRUG: Cyclophosphamide
DRUG: Temozolomide
RADIATION: radiotherapy
DRUG: Regorafenib
Conditions
- • Rhabdomyosarcoma
Find a site
Closest Location:
Queensland Children's Hospital
Research sites nearby
Select from list below to view details:
Queensland Children's Hospital
Brisbane, Not Specified, Australia
Monash Children's Hospital
Clayton, Not Specified, Australia
Perth Children's Hospital
Perth, Not Specified, Australia
Sydney Children's Hospital
Sydney, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Phase 1b Dose finding: VHR induction - IRIVA
| DRUG: Irinotecan
|
ACTIVE_COMPARATOR: CT1A: VHR induction - IVADO
| DRUG: Actinomycin D
|
EXPERIMENTAL: CT1A: VHR Induction IRIVA
| DRUG: Irinotecan
|
ACTIVE_COMPARATOR: CT1B: HR Induction IVA
| DRUG: Actinomycin D
|
EXPERIMENTAL: CT1B: HR Induction IRIVA
| DRUG: Irinotecan
|
EXPERIMENTAL: RT1A: Preoperative Radiotherapy
| RADIATION: radiotherapy
|
ACTIVE_COMPARATOR: RT1A: Post operative radiotherapy
| RADIATION: radiotherapy
|
EXPERIMENTAL: RT1B: Radiotherapy for resectable disease: dose escalated
| RADIATION: radiotherapy
|
ACTIVE_COMPARATOR: RT1B: Radiotherapy for resectable disease: standard dose
| RADIATION: radiotherapy
|
EXPERIMENTAL: RT1C: Radiotherapy for unresectable disease: dose escalated
| RADIATION: radiotherapy
|
ACTIVE_COMPARATOR: RT1C: Radiotherapy for unresectable disease: standard dose
| RADIATION: radiotherapy
|
EXPERIMENTAL: RT2: Radiotherapy to primary tumour and involved lymph nodes
| RADIATION: radiotherapy
|
EXPERIMENTAL: RT2: Radiotherapy to all metastatic sites
| RADIATION: radiotherapy
|
EXPERIMENTAL: CT2A: VHR Maintenance - VC
| DRUG: Vinorelbine
|
NO_INTERVENTION: CT2A: Maintenance -Stop treatment
| Not specified |
EXPERIMENTAL: CT2B: HR Maintenance - VC
| DRUG: Vinorelbine
|
NO_INTERVENTION: CT2B: HR Maintenance - Stop Treatment
| Not specified |
ACTIVE_COMPARATOR: CT3: Relpased Chemotherapy - VIRT
| DRUG: Irinotecan
|
EXPERIMENTAL: CT3: Relapsed Chemotherapy - VIRR
| DRUG: Irinotecan
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Event Free Survival (RT2) | Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm | From randomisation to first failure event, timeframe 36 months |
Event Free Survival (CT1A) | Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm | From randomisation to first failure event, timeframe 36 months |
Event Free Survival (CT1B) | Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm | From randomisation to first failure event, timeframe 36 months |
Event Free Survival (CT2A) | Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm | From randomisation to first failure event, timeframe 36 months |
Event Free Survival (CT2B) | Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm | Time from randomisation to first failure event, timeframe 36 months |
Event Free Survival (CT3) | To determine whether new systemic therapy regimens improve event free survival in relapsed RMS compared to standard therapy (VIRT) (CT3): Initial new systemic therapy combination to be tested: o Regorafenib (R) added to vincristine and irinotecan (VIR) (VIRR) | Patients will be followed up for a minimum of 6 years from trial entry (or 5 years from end of relapsed trial treatment, whichever comes later). Patients will be followed up for progression and death until the end of trial definition has been met. |
Local Failure Free Survival (RT1A and RT1B) | A local failure event is relapse or progression of tumour at the primary site at any time even if there has been a prior /concurrent, regional or distant failure | Time from randomisation to first local failure event, timeframe 36 months |
Local Failure Free Survival (RT1C) | A local failure event is relapse or progression of tumour at the primary site at any time even if there has been a prior /concurrent, regional or distant failure | Time from randomisation to first local failure event, timeframe 36 months |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Recommended Phase II Dose (Phase 1b) | Based on tolerability, where tolerability is evaluated through the occurrence of dose limiting toxicity (DLT). | From first patient first visit in dose finding study until appropriate dose level found, estimated 9 months |
Maximum Tolerated Dose (Phase 1b) | Dose level at which no or one participant experiences a DLT when at least two of three to six participants experience a DLT at the next highest dose. | From first patient first visit in dose finding study until appropriate dose level |
Toxicity (All chemotherapy randomisations) | Categorised and graded using Common Terminology Criteria for Adverse Events | From date of protocol defined treatment until 30 days after the administration of the last treatment |
Dose Limiting Toxicity (Phase 1b) | Diarrhoea: Grade 3 for \>3 days despite loperamide therapy Diarrhoea: Grade 4 despite loperamide therapy. Enterocolitis: Grade 3 or above Ileus: Grade 3 or above for more than 3 days Oral mucositis: Grade 3 above for \>3 days despite optimal supportive care Persistent neutropenia or thrombocytopenia leading to delay of start of next course by \>7 days; i.e. starting \> day 28 Any grade 3 or 4 toxicity resulting in discontinuation of the new combination Any grade 5 toxicity | From commencement of treatment until 21 days after the start of cycle 2 (each cycle is 21 days) |
Response (Phase 1b, CT1A, CT1B) | defined as complete (CR) or partial response (PR) and is clinically defined. Patients who are not assessable for response - e.g. because of early stopping of treatment or death - will be assumed to be non-responders. | Response assessed after course 3 (63 days) and 6 (126 days) |
Tolerability (CT3) | To determine the tolerability of the regimens. | From registration/randomisation until death/study endpoint |
Overall Survival (CT1A) | Death from any cause | From randomisation to death from any cause, assessed for 36 months |
Overall Survival (CT1B) | Death from any cause | From randomisation to death from any cause, assessed for 36 months |
Overall Survival (CT2A) | Death from any cause | From randomisation to death from any cause, assessed for 36 months |
Overall Survival (CT2B) | Death from any cause | From randomisation to death from any cause, assessed for 36 months |
Overall Survival (RT1A and RT1B) | Death from any cause | From randomisation to death from any cause, assessed for 36 months |
Overall Survival (RT1C) | Death from any cause | From RT1C randomisation to death from any cause, assessed for 36 months |
Overall Survival (RT2) | Death from any cause | From RT2 randomisation to death from any cause, as assessed for 36 months |
Overall Survival (CT3) | To evaluate the anti-tumour activity and effect on overall survival of VIRR when compared to standard therapy | Patients will be followed up for a minimum of 6 years from trial entry (or 5 years from end of relapsed trial treatment, whichever comes later). Patients will be followed up for progression and death until the end of trial definition has been met. |
Overall Survival (all patients) | Death from any cause | From randomisation/registration to death from any cause, assessed for 36 months |
Acute wound complications and post-operative complications (RT1A and RT1B) | specific grade 3 and above complications according to CTCAE v 4 and Clavien Dindo scale. Specific wound complications within the same time frame will also be collected | Within 120 days from surgery |
Acute post-radiotherapy complications (All radiotherapy randomisations) | any grade 3 and above event according to CTCAE v 4 | Within 120 days from start of radiotherapy |
Late complications (RT1A, RT1B. RT1C) | specific grade 3 and above events according to CTCAE and Clavien-Dindo scale | After 120 days from last local therapy |
Loco-regional failure-free survival (All radiotherapy randomisations) | A local failure event is relapse or progression of tumour at the primary site at any time even if there has been a prior concurrent local, regional or distant failure. A regional event is relapse or progression of tumour at regional lymph nodes at any time even if there has been a prior distant failure. | From randomisation to first local and/or regional failure event, assessed for 36 months |
Health related quality of life (RT1A and RT2) self-reported questionnaire completed by patient | will be assessed using Pediatric quality of life questionnaire (PedsQL) for the paediatric population (under 18 years). The minimum score is 0 where quality of life is completely unaffected by the intervention to 4 where quality of life is severely affected. | 4 timepoints: 1) 1 day of start of radiotherapy, 2) at completion of radiotherapy, average 5 weeks after start of radiotherapy, 3) 3 months and 4) 24 months following radiotherapy |
Health related quality of life (RT1A and RT2) self-reported questionnaire completed by the patient | will be assessed using European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire 30 (EORTC QLQ-C30) for patients 18 years of age and over. The minimum score is 0 where quality of life is completely unaffected by the intervention to 4 where quality of life is severely affected. | 4 timepoints: 1) 1 day of start of radiotherapy, 2) at completion of radiotherapy, average 5 weeks after start of radiotherapy, 3) 3 months and 4) 24 months following radiotherapy |
Health related quality of life (CT3) self-reported questionnaire completed by the patient | will be assessed using Pediatric quality of life questionnaire (PedsQL) for the paediatric population (under 18 years). The minimum score is 0 where quality of life is completely unaffected by the intervention to 4 where quality of life is severely affected. | 3 timepoints: Each Cycle is 28 days. Timepoint 1: Day 0 of cycle 1 (prior to starting treatment), Timepoint 2 day 0 cycle 3, Timepoint 3) day 0 cycle 5 |
Health related quality of life (CT3) self-reported questionnaire completed by the patient | will be assessed using European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire 30 (EORTC QLQ-C30) for patients 18 years of age and over. The minimum score is 0 where quality of life is completely unaffected by the intervention to 4 where quality of life is severely affected. | 3 timepoints: Each Cycle is 28 days. Timepoint 1: Day 0 of cycle 1 (prior to starting treatment), Timepoint 2 day 0 cycle 3, Timepoint 3) day 0 cycle 5 |
Acceptability and Palatability of Regorafenib (CT3) | "Acceptability and Palatability Questionnaire" To evaluate the acceptability and palatability of regorafenib formulations | 1 timepoint: Day 8 of cycle 1 (Each Cycle is 28 days) |
PET Response (if participating in PET Sub-study) | assessed by PERCIST criteria and visual 'Deauville like' criteria | After three cycles of chemotherapy (each cycle is 21 days) |
Event Free Survival (all patients) | Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm | From date of randomisation/registration to death from any cause, assessed for 36 months |
Event Free Survival (if participating in PET Sub-study) | Failure events are: * Relapse or progression of existing disease, or occurrence of disease at new sites, * Death from any cause without disease progression, * Second malignant neoplasm | From date of randomisation/registration to death from any cause, assessed for 36 months |
Local Failure Free Survival (if participating in PET Sub-study) | A local failure event is relapse or progression of tumour at the primary site at any time even if there has been a prior /concurrent, regional or distant failure | From date of randomisation/registration to first local failure event, assessed for 36 months |
Frequently Asked Questions
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