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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT00742924
Registration number
NCT00742924
Ethics application status
Date submitted
27/08/2008
Date registered
28/08/2008
Date last updated
4/07/2014
Titles & IDs
Public title
Zoledronic Acid and Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Osteosarcoma
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Scientific title
Feasibility and Dose Discovery Analysis of Zoledronic Acid With Concurrent Chemotherapy in the Treatment of Newly Diagnosed Metastatic Osteosarcoma
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Secondary ID [1]
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CDR0000612613
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Secondary ID [2]
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AOST06P1
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Sarcoma
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Condition category
Condition code
Cancer
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Bone
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Cancer
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Sarcoma (also see 'Bone') - soft tissue
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Cancer
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Children's - Other
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - cisplatin
Treatment: Drugs - dexrazoxane hydrochloride
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - etoposide
Treatment: Drugs - ifosfamide
Treatment: Drugs - leucovorin calcium
Treatment: Drugs - methotrexate
Treatment: Drugs - zoledronic acid
Treatment: Surgery - therapeutic conventional surgery
Treatment: Other - filgrastim
Treatment: Drugs - Mesna
Experimental: Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid - (Weeks 1-11) Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; and G-CSF SC. (Week 12) Patients undergo therapeutic conventional surgery .
(Weeks 13-25): Patients receive etoposide IV; ifosfamide IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; G-CSF SC. (Week 26) Patients may undergo surgical procedure.
(Weeks 27-36): Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; etoposide IV; ifosfamide IV; and filgrastim (G-CSF) SC.
See Detailed Description.
Experimental: Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid - (Weeks 1-11) Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; and G-CSF SC. (Week 12) Patients undergo therapeutic conventional surgery.
(Weeks 13-25): Patients receive etoposide IV; ifosfamide IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; G-CSF SC. (Week 26) Patients may undergo surgical procedure.
(Weeks 27-36): Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; etoposide IV; ifosfamide IV; and filgrastim (G-CSF) SC.
See Detailed Description.
Experimental: Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid - (Weeks 1-11) Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; and G-CSF SC. (Week 12) Patients undergo therapeutic conventional surgery.
(Weeks 13-25): Patients receive etoposide IV; ifosfamide IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; G-CSF SC. (Week 26) Patients may undergo surgical procedure.
(Weeks 27-36): Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; etoposide IV; ifosfamide IV; and filgrastim (G-CSF) SC.
See Detailed Description.
Experimental: Chemotherapy and 2.3 mg/m2 Zoledronic Acid after MTD - (Weeks 1-11) Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; and G-CSF SC. (Week 12) Patients undergo therapeutic conventional surgery.
(Weeks 13-25): Patients receive etoposide IV; ifosfamide IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; G-CSF SC. (Week 26) Patients may undergo surgical procedure.
(Weeks 27-36): Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; etoposide IV; ifosfamide IV; and filgrastim (G-CSF) SC.
See Detailed Description.
Treatment: Drugs: cisplatin
Given IV
Treatment: Drugs: dexrazoxane hydrochloride
Given IV
Treatment: Drugs: doxorubicin hydrochloride
Given IV
Treatment: Drugs: etoposide
Given IV
Treatment: Drugs: ifosfamide
Given IV
Treatment: Drugs: leucovorin calcium
Given IV or orally
Treatment: Drugs: methotrexate
Given IV
Treatment: Drugs: zoledronic acid
Given IV
Treatment: Surgery: therapeutic conventional surgery
Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.
Treatment: Other: filgrastim
Given SC
Treatment: Drugs: Mesna
Given IV
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Treatment: Surgery
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Intervention code [3]
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Treatment: Other
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Limiting Toxicity
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Assessment method [1]
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The occurrence of Limiting Toxicity defined as Any CTC AE version 4 Grade 3 and 4 non-hematologic toxicity thought to be possibly, probably or definitely related to zoledronic acid with the specific exclusion of:
* Grade 3 nausea and vomiting controlled with adequate antiemetic prophylaxis.
* Grade 3 transaminase (AST/ALT) that occurs during the evaluation period but resolves to = Grade 2, before the planned dose of therapy after definitive surgery.
* Grade 3 fever or infection.
* Grade 3 or 4 hypocalcemia (see Section 5.1.1)
* Grade 3 mucositis.
* Grade 3 fatigue that returns to = Grade 2, before the planned dose of therapy after definitive surgery.
* Grade 3 joint range of motion, decreased or joint effusion that is related to the primary tumor.
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Timepoint [1]
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Enrollment through the first 12 weeks of therapy.
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Secondary outcome [1]
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Histologic Response as Assessed in the Primary Tumor and in Resected Metastases
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Assessment method [1]
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Histologic response as graded according to the system of Huvos across all specimens resected at the time of local control in the primary tumor and in resected metastases.
The best response, as quantified by maximum necrosis grading according to the system of Huvos across all specimens resected at the time of local control, will be used to quantify the effect of Induction chemotherapy.
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Timepoint [1]
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At definitive surgery planned for 12 weeks after the start of protocol therapy.
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Secondary outcome [2]
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Event-free Survival
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Assessment method [2]
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The EFS and survival functions will be estimated by the Kaplan-Meier methodology.
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Timepoint [2]
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Time from study enrollment to disease recurrence, death without disease progression, diagnosis of a second malignant neoplasm, assessed up to 5 years
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Secondary outcome [3]
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Secondary Limiting Toxicity
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Assessment method [3]
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Secondary limiting toxicity defined as Any CTC AE version 4 Grade 3 and 4 non-hematologic toxicity thought to be possibly, probably or definitely related to zoledronic acid with the specific exclusion of:
* Grade 3 nausea and vomiting controlled with adequate antiemetic prophylaxis.
* Grade 3 transaminase (AST/ALT) that occurs during the evaluation period but resolves to = Grade 2, before the planned dose of therapy after definitive surgery.
* Grade 3 fever or infection.
* Grade 3 or 4 hypocalcemia (see Section 5.1.1)
* Grade 3 mucositis.
* Grade 3 fatigue that returns to = Grade 2, before the planned dose of therapy after definitive surgery.
* Grade 3 joint range of motion, decreased or joint effusion that is related to the primary tumor.
CTC AE version 4 hematologic toxicity will be based on time to blood count recovery to an ANC = 1000/µL and platelet count = 100,000/µL that delays definitive surgery by more than 2 weeks.
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Timepoint [3]
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After week 13 to the end of protocol therapy
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Secondary outcome [4]
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Prognostic Value of Bone Resorption Markers
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Assessment method [4]
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Blood will be collected for quantification of c-telopeptide and urine will be collected for quantification of n-telopeptide.
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Timepoint [4]
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At baseline and at weeks 13 and 36
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Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:
* Biopsy-proven high-grade osteosarcoma within the past 6 weeks
* Newly diagnosed disease
* Metastatic disease
* Resectable disease OR expected to become resectable after initial chemotherapy
* Disease has arisen outside of areas of Paget's disease
PATIENT CHARACTERISTICS:
* ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100% (for patients > 16 years of age) OR Lansky PS 50-100% (for patients = 16 years of age)
* Creatinine clearance or radioisotope glomerular filtration rate = 70 mL/min OR maximum serum creatinine based on age/gender as follows:
* 0.4 mg/dL (for patients 1 to 5 months of age)
* 0.5 mg/dL (for patients 6 to 11 months of age)
* 0.6 mg/dL (for patients 1 year of age)
* 0.8 mg/dL (for patients 2 to 5 years of age)
* 1 mg/dL (for patients 6 to 9 years of age)
* 1.2 mg/dL (for patients 10 to 12 years of age)
* 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
* 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients = 16 years of age)
* Total bilirubin = 1.5 times upper limit of normal (ULN) for age
* AST or ALT < 2.5 times ULN for age
* Shortening fraction = 28% by echocardiogram OR ejection fraction = 50% by radionuclide angiogram
* ANC = 1,000/mm³
* Platelet count = 100,000/mm³ (transfusion independent)
* Hemoglobin = 10 g/dL (RBC transfusion allowed)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use contraception
* No known HIV infection
* No history of pericarditis, myocarditis, symptomatic arrhythmia, or conduction disturbances
PRIOR CONCURRENT THERAPY:
* No prior chemotherapy or radiotherapy
* No other concurrent anticancer chemotherapy
* No concurrent immunomodulating agents
* Steroids for anti-emetic allowed
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Minimum age
No limit
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Maximum age
40
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/08/2008
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Date of last participant enrolment
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Actual
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Date of last data collection
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Actual
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Sample size
Target
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Accrual to date
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Final
24
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Recruitment in Australia
Recruitment state(s)
WA
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Recruitment hospital [1]
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Princess Margaret Hospital for Children - Perth
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Recruitment postcode(s) [1]
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6001 - Perth
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Funding & Sponsors
Primary sponsor type
Other
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Name
Children's Oncology Group
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National Cancer Institute (NCI)
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Ethics approval
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Summary
Brief summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This clinical trial is studying the side effects and best dose of zoledronic acid when given together with combination chemotherapy in treating patients with newly diagnosed metastatic osteosarcoma.
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Trial website
https://clinicaltrials.gov/study/NCT00742924
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Trial related presentations / publications
Goldsby RE, Fan TM, Villaluna D, Wagner LM, Isakoff MS, Meyer J, Randall RL, Lee S, Kim G, Bernstein M, Gorlick R, Krailo M, Marina N. Feasibility and dose discovery analysis of zoledronic acid with concurrent chemotherapy in the treatment of newly diagnosed metastatic osteosarcoma: a report from the Children's Oncology Group. Eur J Cancer. 2013 Jul;49(10):2384-91. doi: 10.1016/j.ejca.2013.03.018. Epub 2013 May 7.
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Public notes
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Contacts
Principal investigator
Name
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Robert Goldsby, MD
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University of California, San Francisco
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT00742924
Download to PDF