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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01222715




Registration number
NCT01222715
Ethics application status
Date submitted
15/10/2010
Date registered
18/10/2010
Date last updated
5/05/2017

Titles & IDs
Public title
Vinorelbine Tartrate and Cyclophosphamide in Combination With Bevacizumab or Temsirolimus in Treating Patients With Recurrent or Refractory Rhabdomyosarcoma
Scientific title
A Randomized Phase II Trial of Bevacizumab (Avastin) and Temsirolimus (Torisel) in Combination With Intravenous Vinorelbine and Cyclophosphamide in Patients With Recurrent/Refractory Rhabdomyosarcoma
Secondary ID [1] 0 0
NCI-2011-02607
Secondary ID [2] 0 0
NCI-2011-02607
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adult Rhabdomyosarcoma 0 0
Childhood Alveolar Rhabdomyosarcoma 0 0
Childhood Pleomorphic Rhabdomyosarcoma 0 0
Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features 0 0
Previously Treated Childhood Rhabdomyosarcoma 0 0
Recurrent Adult Soft Tissue Sarcoma 0 0
Recurrent Childhood 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
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Bevacizumab
Treatment: Drugs - Cyclophosphamide
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Temsirolimus
Treatment: Drugs - Vinorelbine Tartrate

Experimental: Arm I (vinorelbine tartrate, cyclophosphamide, bevacizumab) - Patients receive vinorelbine tartrate IV over 6-10 minutes on days 1 and 8 and cyclophosphamide IV over 30-60 minutes on day 1. Patients also receive bevacizumab IV over 30-90 minutes on day 1.

Experimental: Arm II (vinorelbine tartrate, cyclophosphamide, temsirolimus) - Patients receive vinorelbine tartrate and cyclophosphamide as in arm I. Patients also receive temsirolimus IV over 30-60 minutes on days 1, 8, and 15.


Other interventions: Bevacizumab
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Temsirolimus
Given IV

Treatment: Drugs: Vinorelbine Tartrate
Given IV
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Free Survival Probability
Timepoint [1] 0 0
1 year
Primary outcome [2] 0 0
Rate of Dose-Limiting Toxicities
Timepoint [2] 0 0
From the date of randomization until a maximum of 12 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities.
Secondary outcome [1] 0 0
Response Rate (CR + PR)
Timepoint [1] 0 0
From the date of randomization until a maximum of 2 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities.

Eligibility
Key inclusion criteria
- Diagnosis

- Patients with first relapse or progression of rhabdomyosarcoma are eligible

- Patients with primary refractory disease are eligible

- Primary refractory disease is defined as first progression after receiving
at least one course of cyclophosphamide or ifosfamide containing
chemotherapy without prior demonstration of a radiographic response to
chemotherapy (progression on irinotecan-containing chemotherapy without
cyclophosphamide or ifosfamide containing chemotherapy will not be
considered a first progression)

- Note: Patients without measurable or evaluable disease are eligible

- Patients must have had a previous histological verification of rhabdomyosarcoma at
original diagnosis

- Patients must have a Karnofsky or Lansky performance status score of >= 50%,
corresponding to Eastern Cooperative Oncology Group (ECOG) categories of 0, 1, or 2;
use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of
age

- Patients must have a life expectancy of >= 8 weeks

- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study

- Myelosuppressive chemotherapy: Must not have received within 3 weeks prior to entry
onto this study (4 weeks if prior nitrosourea)

- Biologic (anti-neoplastic agent):

- Patients may have received prior therapy with oral tyrosine kinase inhibitors or
other similar agents; at least 7 days must have elapsed since the completion of
therapy with a biologic agent and all toxicities must have resolved to < grade 2
prior to enrollment

- 3 half-lives (or 6 weeks) must have elapsed since previous monoclonal antibody
therapy prior to enrollment on this study

- Myeloid growth factor: Must not have received within 1 week prior to entry onto this
study

- Radiation therapy (RT): At least 4 weeks must have elapsed between RT and study entry;
previously radiated lesions cannot be used to assess response unless those sites are
the sites of disease progression

- Stem cell transplant (SCT): For autologous SCT, >= 3 months must have elapsed; for
allogeneic SCT, >= 6 months must have elapsed and no evidence of active graft vs. host
disease

- Patients must have recovered from any surgical procedure before enrolling on this
study

- Minor surgical procedures (e.g., biopsies involving core or fine-needle
aspiration procedures, infusaport or Broviac line placement, paracentesis, or
thoracocentesis) need to have fully healed and occurred > 7 days prior to
enrollment

- Patients who have had a major surgical procedure (such as laparotomy,
thoracotomy, open biopsy, or resection of tumor) can only be enrolled on study >
28 days from such procedure

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

- Platelet count >= 75,000/µL (transfusion independent, defined as without transfusion
for >= 1 week prior to enrollment)

- Hemoglobin >= 8.0 g/dL (may receive packed red blood cells [PRBC] transfusions)

- Bone marrow disease involvement of tumor is allowed, however, peripheral blood count
criteria must still be met

- 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:

- =< 0.4 mg/dL (for patients aged 1 month to < 6 months)

- =< 0.5 mg/dL (for patients aged 6 months to < 1 year)

- =< 0.6 mg/dL (for patients aged 1 to < 2 years)

- =< 0.8 mg/dL (for patients aged 2 to < 6 years)

- =< 1 mg/dL (for patients aged 6 to < 10 years)

- =< 1.2 mg/dL (for patients aged 10 to < 13 years)

- =< 1.4 mg/dL (for female patients aged >= 13 years)

- =< 1.5 mg/dL (for male patients aged 13 to < 16 years)

- =< 1.7 mg/dL (for male patients aged >= 16 years)

- Urine protein level:

- Patients aged =< 17 years: Urine protein to creatinine (UPC) ratio should be
calculated; UPC ratio must be =< 1 for patient to be eligible

- Patients aged > 17 years: Urine protein should be screened by urine analysis; if
protein is 2+ or higher, 24-hour urine protein must be obtained and the level
must be < 1,000 mg for patient enrollment

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

- Shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 50% by
radionuclide angiogram
Minimum age
No limit
Maximum age
29 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with botryoid histology, any stage or group, are ineligible

- Patients with embryonal histology, stage I or clinical group 1 at initial disease
presentation, who present with local or regional recurrence, are ineligible

- Patients who previously received craniospinal irradiation are ineligible

- Patients who previously received vinorelbine, bevacizumab, temsirolimus, or any other
direct vascular endothelial growth factor (VEGF)/vascular endothelial growth factor
receptor (VEGFR-) or mammalian target of rapamycin (mTOR-) targeting agents are
ineligible

- Patients with known central nervous system (CNS) disease (excluding
intracranial/intraspinal extension secondary to local progression of a parameningeal
or paraspinal primary), except for those with treated brain metastasis, are ineligible

- Treated brain metastases are defined as having no ongoing requirement for
steroids and no evidence of progression or hemorrhage after treatment for at
least 3 months, as ascertained by clinical examination and brain imaging
(magnetic resonance imaging [MRI] or computed tomography [CT]); stable dose of
anticonvulsants are allowed; treatment for brain metastases may include
whole-brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, linear
accelerator [LINAC], or equivalent), or a combination as deemed appropriate by
the treating physician

- Patients with CNS metastases treated within 3 months prior to enrollment by
neurosurgical resection or brain biopsy are ineligible

- Patients who receive radiation or chemotherapy (inclusive of palliative intent) for
first disease progression or relapse of rhabdomyosarcoma prior to enrollment are
ineligible

- Female patients who are pregnant are ineligible

- Lactating females are not eligible unless they have agreed to discontinue
breastfeeding

- Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained

- Sexually active patients of reproductive potential are not eligible unless they have
agreed to use an effective contraceptive method for the duration of their study
participation

- Patients with a documented chronic non-healing wound, ulcer, or significant trauma
injury (those with bone fractures, including pathological fractures, or requiring
surgical intervention) within 28 days prior to beginning therapy are ineligible

- Patients with evidence of intratumoral hemorrhage, gastrointestinal bleeding, or on
anticoagulation for thrombosis or history of thrombosis are ineligible

- Patients with uncontrolled hypertension are ineligible; uncontrolled hypertension is
defined as follows:

- Patients aged =< 17 years: greater than 95th percentile systolic and diastolic
blood pressure based on age and height that is not controlled by one
antihypertensive medication

- Patients aged > 17 years: systolic blood pressure >= 160 mm Hg and/or diastolic
blood pressure >= 90 mm Hg that is not controlled by one antihypertensive
medication

- Patients currently taking anticoagulants or antiplatelet agents with the exception of
aspirin (=< 81 mg/day) are ineligible

- Patients with history of central venous catheter (CVC)-associated thrombosis requiring
systemic anticoagulation are ineligible; Note: Patients with history of sluggish flow
from CVC or CVC-associated thrombosis treated with tissue plasminogen activator (TPA)
only are not excluded

- Patients with clinically significant cardiovascular disease are excluded:

- History of cerebrovascular accident (CVA) within the prior 6 months

- Myocardial infarction or unstable angina within the prior 6 months

- New York Heart Association grade 2 or greater congestive heart failure

- Serious and inadequately controlled cardiac arrhythmia

- Significant vascular disease (e.g., aortic aneurysm, history of aortic
dissection)

- Clinically significant peripheral vascular disease

- Patients diagnosed with rhabdomyosarcoma as a second malignant neoplasm are not
eligible

- Patients with history of any second malignant neoplasm who have received chemotherapy
or radiation for the treatment of that malignancy 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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2015
Sample size
Target
Accrual to date
Final
87
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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Arkansas
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California
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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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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New Mexico
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Dakota
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Tennessee
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Utah
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Vermont
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West Virginia
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Wisconsin
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Alberta
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British Columbia
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Manitoba
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Newfoundland and Labrador
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Nova Scotia
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Ontario
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Quebec
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Saskatchewan
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New Zealand
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Auckland
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New Zealand
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Christchurch

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 II trial studies how well vinorelbine tartrate and cyclophosphamide
work in combination with bevacizumab or temsirolimus in treating patients with recurrent or
refractory rhabdomyosarcoma. Drugs used in chemotherapy, such as vinorelbine tartrate and
cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing
the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can
block tumor growth in different ways. Some block the ability of tumor cells to grow and
spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
Bevacizumab may also stop the growth of rhabdomyosarcoma by blocking blood flow to the tumor.
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 is more effective when
given together with bevacizumab or temsirolimus in treating rhabdomyosarcoma.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01222715
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Leo Mascarenhas
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/ct2/show/NCT01222715