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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02484443




Registration number
NCT02484443
Ethics application status
Date submitted
26/06/2015
Date registered
29/06/2015
Date last updated
18/06/2020

Titles & IDs
Public title
Dinutuximab in Combination With Sargramostim in Treating Patients With Recurrent Osteosarcoma
Scientific title
A Phase 2 Study of Human-Mouse Chimeric Anti-disialoganglioside Monoclonal Antibody ch14.18 (Dinutuximab, NSC# 764038) in Combination With Sargramostim (GM-CSF) in Patients With Recurrent Osteosarcoma
Secondary ID [1] 0 0
NCI-2015-01001
Secondary ID [2] 0 0
NCI-2015-01001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Malignant Neoplasm in the Lung 0 0
Metastatic Osteosarcoma 0 0
Recurrent Osteosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Dinutuximab
Other interventions - Laboratory Biomarker Analysis
Other interventions - Pharmacological Study
Other interventions - Sargramostim

Experimental: Treatment (sargramostim and dinutuximab) - Patients receive sargramostim SC QD on days 1-14 and dinutuximab IV over 10 hours on days 4-7 (dinutuximab infusion may be extended up to a total of 20 hours per day for anticipated toxicities). Treatment repeats every 28 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.


Other interventions: Dinutuximab
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Other interventions: Pharmacological Study
Correlative studies

Other interventions: Sargramostim
Given SC

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease control - The probability of remaining event-free as a function of time since enrollment will be estimated by the method of Kaplan and Meier. The complementary log-log transformation of the Kaplan-Meier estimate of the 12 month disease control probability will be used to construct confidence intervals of that probability. Only patients who can be confirmed to be free of detectable disease 12 months after enrollment, without intervening disease progression, will be considered to have experienced 12 month disease control.
Timepoint [1] 0 0
During the first 12 months
Secondary outcome [1] 0 0
Pharmacokinetics of dinutuximab - The average and standard deviation of estimates will be reported.
Timepoint [1] 0 0
Baseline, 4 hours, and immediately before end of dinutuximab infusion on day 4, 4 hours before, immediately before, 4-8 hours, and 4-10 days following dinutuximab infusion on day 5 of course 1, and then prior to the start of course 2
Secondary outcome [2] 0 0
Incidence of unacceptable toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 - A Bayesian rule will be used to monitor for excessive toxicity. Descriptive analyses of this safety information will be performed and will include the incidence of adverse events, severe adverse events, serious adverse events, and fatal adverse events. Type, frequency, and severity of laboratory abnormalities will also be analyzed.
Timepoint [2] 0 0
Up to 4 years

Eligibility
Key inclusion criteria
- Patients must have histologic diagnosis of osteosarcoma at original diagnosis

- Patients must have had at least one episode of disease recurrence in the lungs without
limitation on number of episodes of recurrence as long as they meet the following
criteria:

- Surgical resection of all possible sites of suspected pulmonary metastases in
order to achieve a complete remission within 4 weeks prior to study enrollment**

- Pathologic confirmation of metastases from at least one of the resected sites

- For patients with bilateral pulmonary metastases, resection must be
performed from both lungs and the study enrollment must be within 4 weeks
from date of the last lung surgery

- Note: If surgery related changes such as atelectasis are seen on the
post-operative computed tomography (CT) scan, patients will remain eligible to
enroll as long as the operating surgeon believes that all sites of metastases
were resected; patients with positive microscopic margins will be eligible to
enroll

- Patient must have adequate tumor specimen available for submission

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

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

- Myelosuppressive anti-cancer therapy: must not have been received within 2 weeks
of study entry (4 weeks if prior nitrosourea)

- Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy
with a biologic agent

- Radiation therapy (RT): >= 2 weeks for local palliative radiation therapy (RT)
(small port); >= 6 weeks must have elapsed if prior craniospinal RT or if >= 50%
radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone
marrow (BM) radiation

- Surgery: >= 2 weeks from last major surgery, including pulmonary metastasectomy,
with the exclusion of a central line placement and core needle or small open
biopsies

- Patient must not have received pegfilgrastim within 14 days of enrollment

- Patient must not have received filgrastim (G-CSF, Neupogen) within 7 days of
enrollment

- Patient must not have received immune suppressants: corticosteroids (for other than
allergic reactions and anaphylaxis), cyclosporine or tacrolimus within 7 days of
enrollment

- Note: the use of topical and/or inhalational steroids is allowed

- Total absolute phagocyte count (APC = [%neutrophils + %monocytes) x white blood cells
[WBC]) is at least 1000/uL

- Platelet count >= 50,000/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: 0.4 (male) 0.4 (female)

- 6 months to < 1 year: 0.5 (male), 0.5 (female)

- 1 to < 2 years: 0.6 (male), 0.6 (female)

- 2 to < 6 years: 0.8 (male), 0.8 (female)

- 6 to < 10 years: 1 (male), 1 (female)

- 10 to < 13 years: 1.2 (male), 1.2 (female)

- 13 to < 16 years: 1.5 (male), 1.4 (female)

- >= 16 years: 1.7 (male), 1.4 (female)

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

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110
U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)

- Serum albumin >= 2 g/dL

- Baseline electrocardiogram (EKG) shows normal corrected QT interval (QTc) interval of
=< 470 milliseconds (ms)

- Shortening fraction of >= 27% by echocardiogram, or

- Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram

- No evidence of dyspnea at rest, no history of exercise intolerance, and a pulse
oximetry > 94%

- Patient has no known history of seizure disorder

- Central nervous system (CNS) toxicity including peripheral neuropathy =< grade 2
Minimum age
No limit
Maximum age
29 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with distant bone metastases at original diagnosis or relapse (patients with
only skip lesions will be eligible)

- Patients with concurrent local and pulmonary recurrence at the time of enrollment;
note: patients who had local recurrence previously that has been treated and now
present with an isolated pulmonary recurrence and meet the surgical resection criteria
stated above will be eligible

- Patients with primary refractory disease with progression of the primary tumor on
initial therapy

- Patients with CNS disease or other sites of extra-pulmonary metastases at the time of
most recent episode of disease recurrence preceding enrollment

- Patients with a prior hypersensitivity reaction to sargramostim

- Patients who have received prior anti-GD2 therapy, including chimeric antigen receptor
(CAR) T cells directed against GD2 antigen

- Female patients who are pregnant are ineligible

- Lactating females are not eligible unless they have agreed not to breastfeed their
infants

- 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 should maintain adequate contraception for a minimum of 2
months after the last dose of ch14.18 (dinutuximab)

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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,SA,VIC,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
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [6] 0 0
Monash Medical Center-Clayton Campus - Clayton
Recruitment hospital [7] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [8] 0 0
Princess Margaret Hospital for Children - 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
5006 - North Adelaide
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3052 - Parkville
Recruitment postcode(s) [8] 0 0
6008 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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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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Minnesota
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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 York
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North Carolina
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North Dakota
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Ohio
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South Carolina
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South Dakota
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Tennessee
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Texas
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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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Manitoba
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Nova Scotia
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Ontario
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Quebec
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New Zealand
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Auckland
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New Zealand
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Christchurch
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Puerto Rico
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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 phase II trial studies how well dinutuximab works when given with sargramostim in
treating patients with osteosarcoma that has come back after treatment (recurrent).
Monoclonal antibodies, such as dinutuximab, may find tumor cells and help kill them.
Sargramostim may help the body increase the amount of white blood cells it produces, which
help the body fight off infections. Giving dinutuximab with sargramostim may work better and
kill more cancer cells.
Trial website
https://clinicaltrials.gov/show/NCT02484443
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pooja Hingorani
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
Other publications