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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02567435




Registration number
NCT02567435
Ethics application status
Date submitted
2/10/2015
Date registered
5/10/2015
Date last updated
9/07/2020

Titles & IDs
Public title
Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
Scientific title
A Randomized Phase 3 Study of Vincristine, Dactinomycin, Cyclophosphamide (VAC) Alternating With Vincristine and Irinotecan (VI) Versus VAC/VI Plus Temsirolimus (TORI, Torisel, NSC# 683864) in Patients With Intermediate Risk (IR) Rhabdomyosarcoma (RMS)
Secondary ID [1] 0 0
NCI-2015-01644
Secondary ID [2] 0 0
NCI-2015-01644
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alveolar Rhabdomyosarcoma 0 0
Botryoid-Type Embryonal Rhabdomyosarcoma 0 0
Embryonal Rhabdomyosarcoma 0 0
Rhabdomyosarcoma 0 0
Sclerosing Rhabdomyosarcoma 0 0
Spindle Cell Rhabdomyosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cyclophosphamide
Other interventions - Dactinomycin
Treatment: Drugs - Irinotecan Hydrochloride
Other interventions - Laboratory Biomarker Analysis
Other interventions - Questionnaire Administration
Treatment: Other - Radiation Therapy
Treatment: Drugs - Temsirolimus
Treatment: Drugs - Vincristine Sulfate
Treatment: Drugs - Vinorelbine

Experimental: Regimen A (VAC/VI) - Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. Patients also undergo primary site RT beginning at week 13 or metastatic site RT beginning at week 43 for up to 6.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then receive vinorelbine IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide PO QD on days 1-28. Cycles repeats every 28 days for 24 weeks in the absence of disease progression or unacceptable toxicity.

Experimental: Regimen B (VAC/VI/temsirolimus) - Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37 and temsirolimus IV over 30-60 minutes on day 1 of weeks 1-12 and 21-42. Patients also undergo RT as in Regimen A. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then receive vinorelbine IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide PO QD on days 1-28. Cycles repeats every 28 days for 24 weeks in the absence of disease progression or unacceptable toxicity.

Experimental: Regimen C (FOXO1 fusion negative, VAC/VA) - Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-10 and 13-22, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, and 22, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients undergo RT beginning at week 13 for up to 6.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.


Treatment: Drugs: Cyclophosphamide
Given IV and PO

Other interventions: Dactinomycin
Given IV

Treatment: Drugs: Irinotecan Hydrochloride
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Other interventions: Questionnaire Administration
Ancillary studies

Treatment: Other: Radiation Therapy
Undergo RT

Treatment: Drugs: Temsirolimus
Given IV

Treatment: Drugs: Vincristine Sulfate
Given IV

Treatment: Drugs: Vinorelbine
Given IV

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-free survival (EFS) - EFS distributions will be estimated using the Kaplan-Meier method and will be compared between the randomized treatment groups using the log-rank test.
Timepoint [1] 0 0
Time from study enrollment to the first occurrence of progression, relapse, second malignant neoplasm or death as a first event
Secondary outcome [1] 0 0
Overall survival (OS) - OS distributions will be estimated using the Kaplan-Meier method and will be compared between the randomized treatment groups using the log-rank test.
Timepoint [1] 0 0
Time from study enrollment to death from any cause, assessed up to 10 years

Eligibility
Key inclusion criteria
- Feasibility Phase: Patients must be < 21 years of age at the time of enrollment;
please note: the feasibility phase is complete, effective with amendment #1

- Efficacy Phase: Patients must be =< 40 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

- RMS types included under embryonal rhabdomyosarcoma (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 2013 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
rhabdomyosarcoma (ARMS) in the 2013 WHO classification is the same as in the ICR and
includes classic and solid variants

- ERMS

- Stage 1, group III (non-orbit)

- Stage 3, group I/II

- Stage 2/3, group III

- Stage 4, group IV, < 10 years old

- ARMS:

- Stages 1-3, groups I-III

- Specimen Submission: Patients must have sufficient tissue available for the required
biology study

- Lansky performance status score >= 50 for patients =< 16 years of age; Karnofsky
performance status score >= 50 for patients > 16 years of age

- Peripheral absolute neutrophil count (ANC) >= 750/uL

- Platelet count >= 75,000/uL

- 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:

- 1 month to < 6 months old: 0.4 mg/dl (male), 0.4 mg/dl (female)

- 6 months to < 1 year old: 0.5 mg/dl (male), 0.5 mg/dl (female)

- 1 to < 2 years old: 0.6 mg/dl (male), 0.6 mg/dl (female)

- 2 to < 6 years old: 0.8 mg/dl (male), 0.8 mg/dl (female)

- 6 to < 10 years old: 1 mg/dl (male), 1 mg/dl (female)

- 10 to < 13 years old: 1.2 mg/dl (male), 1.2 mg/dl (female)

- 13 to < 16 years old: 1.5 mg/dl (male), 1.4 mg/dl (female)

- >= 16 years old: 1.7 mg/dl (male), 1.4 mg/dl (female)

- Patients with an elevated serum creatinine due to obstructive hydronephrosis
secondary to tumor are still eligible; however, patients with urinary tract
obstruction by tumor must have unimpeded urinary flow established via diversion
(i.e. percutaneous nephrostomies or ureteric stents) of the urinary tract

- Total bilirubin =< 1.5 x upper limit of normal (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.
Minimum age
No limit
Maximum age
40 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients who have previously received temsirolimus, another mTOR inhibitor, or any
other investigational agent

- Patients who have received any chemotherapy (excluding steroids) and/or RT prior to
this enrollment

- Patients with uncontrolled hyperglycemia

- Patients with uncontrolled hyperlipidemia

- Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation and for
at least 3 months after treatment is completed

- Female patients who are pregnant are not eligible; Note: a pregnancy test is required
for female patients of childbearing potential prior to study entry

- Lactating females who plan to breastfeed their infants are not eligible

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [5] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [6] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
6008 - Perth
Recruitment postcode(s) [6] 0 0
6009 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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United States of America
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Alaska
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Arizona
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Arkansas
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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San Juan

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This randomized phase III trial studies how well combination chemotherapy (vincristine
sulfate, dactinomycin, cyclophosphamide alternated with vincristine sulfate and irinotecan
hydrochloride or vinorelbine) works compared to combination chemotherapy plus temsirolimus in
treating patients with rhabdomyosarcoma (cancer that forms in the soft tissues, such as
muscle), and has an intermediate chance of coming back after treatment (intermediate risk).
Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either
by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Combination chemotherapy and temsirolimus may stop the growth of tumor cells by blocking some
of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy
or combination chemotherapy plus temsirolimus is more effective in treating patients with
intermediate-risk rhabdomyosarcoma.
Trial website
https://clinicaltrials.gov/show/NCT02567435
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Abha A Gupta
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02567435