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Trial record 8 of 13 for:    "Bone Osteosarcoma" | "Bone Density Conservation Agents"

Zoledronic Acid and Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Osteosarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00742924
Recruitment Status : Completed
First Posted : August 28, 2008
Results First Posted : July 4, 2014
Last Update Posted : July 4, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Sarcoma
Interventions Drug: cisplatin
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: leucovorin calcium
Drug: methotrexate
Drug: zoledronic acid
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
Biological: filgrastim
Drug: Mesna
Enrollment 24
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD
Hide Arm/Group Description

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

Period Title: Overall Study
Started 6 6 6 6
Completed 1 4 2 0
Not Completed 5 2 4 6
Reason Not Completed
Adverse Event             0             0             1             1
Lack of Efficacy             5             1             2             4
Physician Decision             0             0             0             1
Withdrawal by Subject             0             1             1             0
Arm/Group Title Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD Total
Hide Arm/Group Description

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

Total of all reporting groups
Overall Number of Baseline Participants 6 6 6 6 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 6 participants 6 participants 24 participants
11.5
(8 to 20)
15.5
(9 to 21)
14
(10 to 19)
14.5
(7 to 22)
13.5
(7 to 22)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 24 participants
Female
5
  83.3%
4
  66.7%
2
  33.3%
5
  83.3%
16
  66.7%
Male
1
  16.7%
2
  33.3%
4
  66.7%
1
  16.7%
8
  33.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 24 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
1
   4.2%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  33.3%
1
  16.7%
3
  50.0%
1
  16.7%
7
  29.2%
White
4
  66.7%
4
  66.7%
2
  33.3%
3
  50.0%
13
  54.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
  16.7%
1
  16.7%
1
  16.7%
3
  12.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 24 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
  16.7%
2
  33.3%
3
  12.5%
Not Hispanic or Latino
6
 100.0%
5
  83.3%
5
  83.3%
4
  66.7%
20
  83.3%
Unknown or Not Reported
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
1
   4.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 24 participants
United States 4 5 5 6 20
Canada 2 1 1 0 4
1.Primary Outcome
Title Limiting Toxicity
Hide Description

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.
Time Frame Enrollment through the first 12 weeks of therapy.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome
Arm/Group Title Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD
Hide Arm/Group Description:

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Number
Unit of Measure: participants
1 1 3 2
2.Secondary Outcome
Title Histologic Response as Assessed in the Primary Tumor and in Resected Metastases
Hide Description

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.

Time Frame At definitive surgery planned for 12 weeks after the start of protocol therapy.
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Event-free Survival
Hide Description The EFS and survival functions will be estimated by the Kaplan-Meier methodology.
Time Frame Time from study enrollment to disease recurrence, death without disease progression, diagnosis of a second malignant neoplasm, assessed up to 5 years
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Secondary Limiting Toxicity
Hide Description

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.

Time Frame After week 13 to the end of protocol therapy
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Prognostic Value of Bone Resorption Markers
Hide Description Blood will be collected for quantification of c-telopeptide and urine will be collected for quantification of n-telopeptide.
Time Frame At baseline and at weeks 13 and 36
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD
Hide Arm/Group Description

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

(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.

cisplatin: Given IV

dexrazoxane hydrochloride: Given IV

doxorubicin hydrochloride: Given IV

etoposide: Given IV

ifosfamide: Given IV

leucovorin calcium: Given IV or orally

All-Cause Mortality
Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   6/6 (100.00%)   6/6 (100.00%)   5/6 (83.33%) 
Blood and lymphatic system disorders         
Anemia  3/6 (50.00%)  4/6 (66.67%)  2/6 (33.33%)  1/6 (16.67%) 
Febrile neutropenia  2/6 (33.33%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%) 
Ear and labyrinth disorders         
Hearing impaired  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders         
Gingival pain  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Mucositis oral  0/6 (0.00%)  0/6 (0.00%)  3/6 (50.00%)  0/6 (0.00%) 
Nausea  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Oral pain  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Vomiting  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
General disorders         
Edema limbs  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Infections and infestations         
Enterocolitis infectious  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Eye infection  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Infections and infestations - Other, specify  2/6 (33.33%)  2/6 (33.33%)  2/6 (33.33%)  0/6 (0.00%) 
Upper respiratory infection  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Injury, poisoning and procedural complications         
Fracture  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Investigations         
Alanine aminotransferase increased  3/6 (50.00%)  4/6 (66.67%)  2/6 (33.33%)  1/6 (16.67%) 
Aspartate aminotransferase increased  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%) 
Lymphocyte count decreased  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  1/6 (16.67%) 
Neutrophil count decreased  3/6 (50.00%)  5/6 (83.33%)  4/6 (66.67%)  3/6 (50.00%) 
Platelet count decreased  3/6 (50.00%)  4/6 (66.67%)  2/6 (33.33%)  1/6 (16.67%) 
White blood cell decreased  4/6 (66.67%)  5/6 (83.33%)  2/6 (33.33%)  2/6 (33.33%) 
Metabolism and nutrition disorders         
Anorexia  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%) 
Dehydration  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  1/6 (16.67%) 
Hyperglycemia  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Hypermagnesemia  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Hypocalcemia  2/6 (33.33%)  2/6 (33.33%)  6/6 (100.00%)  1/6 (16.67%) 
Hypokalemia  2/6 (33.33%)  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%) 
Hyponatremia  1/6 (16.67%)  0/6 (0.00%)  3/6 (50.00%)  1/6 (16.67%) 
Hypophosphatemia  0/6 (0.00%)  3/6 (50.00%)  3/6 (50.00%)  1/6 (16.67%) 
Musculoskeletal and connective tissue disorders         
Pain in extremity  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Vascular disorders         
Hypotension  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 352-273-0558
EMail: resultsreportingcoordinator@childrensoncologygroup.org
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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00742924     History of Changes
Other Study ID Numbers: AOST06P1
CDR0000612613 ( Other Identifier: Clinical Trials.gov )
COG-AOST06P1 ( Other Identifier: Children's Oncology Group )
First Submitted: August 27, 2008
First Posted: August 28, 2008
Results First Submitted: June 4, 2014
Results First Posted: July 4, 2014
Last Update Posted: July 4, 2014