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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02484443
Ethics application status
Date submitted
26/06/2015
Date registered
29/06/2015
Date last updated
26/10/2023

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
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
Treatment: Other - Dinutuximab
Other interventions - Laboratory Biomarker Analysis
Other interventions - Pharmacological Study
Treatment: Other - 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.


Treatment: Other: Dinutuximab
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Other interventions: Pharmacological Study
Correlative studies

Treatment: Other: Sargramostim
Given SC
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease Control
Timepoint [1] 0 0
12 months after study enrollment
Secondary outcome [1] 0 0
T 1/2 Alpha of the Serum Concentration of Dinutuximab
Timepoint [1] 0 0
Cycle 1 Day 4 and Day 7: pre-infusion, hour 4-6, end of infusion, 4-8 hours post infusion. Once between days 11-17. Cycle 2 Day 0 or 1
Secondary outcome [2] 0 0
T 1/2 Beta of the Serum Concentration of Dinutuximab
Timepoint [2] 0 0
Cycle 1 Day 4 and Day 7: pre-infusion, hour 4-6, end of infusion, 4-8 hours post infusion. Once between days 11-17. Cycle 2 Day 0 or 1
Secondary outcome [3] 0 0
Maximum of Concentration (Cmax) of the Serum Concentration Dinutuximab
Timepoint [3] 0 0
Cycle 1 Day 4 and Day 7: pre-infusion, hour 4-6, end of infusion, 4-8 hours post infusion. Once between days 11-17. Cycle 2 Day 0 or 1
Secondary outcome [4] 0 0
Area Under the Curve (AUC)0 to Infinity of Serum Dinutuximab
Timepoint [4] 0 0
Cycle 1 Day 4 and Day 7: pre-infusion, hour 4-6, end of infusion, 4-8 hours post infusion. Once between days 11-17. Cycle 2 Day 0 or 1
Secondary outcome [5] 0 0
Number of Cycles Where an Unacceptable Toxicity as Defined in the Protocol Using The National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 Was Observed
Timepoint [5] 0 0
5 cycles of protocol therapy planned as 140 days

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
Sex
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
NA
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/02/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/09/2023
Sample size
Target
Accrual to date
Final
41
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
State/province [9] 0 0
Florida
Country [10] 0 0
United States of America
State/province [10] 0 0
Georgia
Country [11] 0 0
United States of America
State/province [11] 0 0
Hawaii
Country [12] 0 0
United States of America
State/province [12] 0 0
Idaho
Country [13] 0 0
United States of America
State/province [13] 0 0
Illinois
Country [14] 0 0
United States of America
State/province [14] 0 0
Indiana
Country [15] 0 0
United States of America
State/province [15] 0 0
Iowa
Country [16] 0 0
United States of America
State/province [16] 0 0
Kentucky
Country [17] 0 0
United States of America
State/province [17] 0 0
Louisiana
Country [18] 0 0
United States of America
State/province [18] 0 0
Maine
Country [19] 0 0
United States of America
State/province [19] 0 0
Maryland
Country [20] 0 0
United States of America
State/province [20] 0 0
Massachusetts
Country [21] 0 0
United States of America
State/province [21] 0 0
Michigan
Country [22] 0 0
United States of America
State/province [22] 0 0
Minnesota
Country [23] 0 0
United States of America
State/province [23] 0 0
Mississippi
Country [24] 0 0
United States of America
State/province [24] 0 0
Missouri
Country [25] 0 0
United States of America
State/province [25] 0 0
Nebraska
Country [26] 0 0
United States of America
State/province [26] 0 0
Nevada
Country [27] 0 0
United States of America
State/province [27] 0 0
New Hampshire
Country [28] 0 0
United States of America
State/province [28] 0 0
New Jersey
Country [29] 0 0
United States of America
State/province [29] 0 0
New York
Country [30] 0 0
United States of America
State/province [30] 0 0
North Carolina
Country [31] 0 0
United States of America
State/province [31] 0 0
North Dakota
Country [32] 0 0
United States of America
State/province [32] 0 0
Ohio
Country [33] 0 0
United States of America
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Oklahoma
Country [34] 0 0
United States of America
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Oregon
Country [35] 0 0
United States of America
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Pennsylvania
Country [36] 0 0
United States of America
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South Carolina
Country [37] 0 0
United States of America
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South Dakota
Country [38] 0 0
United States of America
State/province [38] 0 0
Tennessee
Country [39] 0 0
United States of America
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Texas
Country [40] 0 0
United States of America
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Utah
Country [41] 0 0
United States of America
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Vermont
Country [42] 0 0
United States of America
State/province [42] 0 0
Virginia
Country [43] 0 0
United States of America
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Washington
Country [44] 0 0
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West Virginia
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United States of America
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Wisconsin
Country [46] 0 0
Canada
State/province [46] 0 0
Alberta
Country [47] 0 0
Canada
State/province [47] 0 0
Manitoba
Country [48] 0 0
Canada
State/province [48] 0 0
Nova Scotia
Country [49] 0 0
Canada
State/province [49] 0 0
Ontario
Country [50] 0 0
Canada
State/province [50] 0 0
Quebec
Country [51] 0 0
New Zealand
State/province [51] 0 0
Auckland
Country [52] 0 0
New Zealand
State/province [52] 0 0
Christchurch
Country [53] 0 0
Puerto Rico
State/province [53] 0 0
San Juan

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02484443