Trial Outcomes & Findings for Zoledronic Acid and Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Osteosarcoma (NCT NCT00742924)
NCT ID: NCT00742924
Last Updated: 2014-07-04
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Enrollment through the first 12 weeks of therapy.
Results posted on
2014-07-04
Participant Flow
Participant milestones
| Measure |
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.
cisplatin: Given IV
dexrazoxane hydrochloride: Given IV
doxorubicin hydrochloride: Given IV
etoposide: Given IV
ifosfamide: Given IV
leucovorin calcium: Given IV or orally
|
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.
cisplatin: Given IV
dexrazoxane hydrochloride: Given IV
doxorubicin hydrochloride: Given IV
etoposide: Given IV
ifosfamide: Given IV
leucovorin calcium: Given IV or orally
|
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.
cisplatin: Given IV
dexrazoxane hydrochloride: Given IV
doxorubicin hydrochloride: Given IV
etoposide: Given IV
ifosfamide: Given IV
leucovorin calcium: Given IV or orally
|
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.
cisplatin: Given IV
dexrazoxane hydrochloride: Given IV
doxorubicin hydrochloride: Given IV
etoposide: Given IV
ifosfamide: Given IV
leucovorin calcium: Given IV or orally
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
6
|
|
Overall Study
COMPLETED
|
1
|
4
|
2
|
0
|
|
Overall Study
NOT COMPLETED
|
5
|
2
|
4
|
6
|
Reasons for withdrawal
| Measure |
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.
cisplatin: Given IV
dexrazoxane hydrochloride: Given IV
doxorubicin hydrochloride: Given IV
etoposide: Given IV
ifosfamide: Given IV
leucovorin calcium: Given IV or orally
|
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.
cisplatin: Given IV
dexrazoxane hydrochloride: Given IV
doxorubicin hydrochloride: Given IV
etoposide: Given IV
ifosfamide: Given IV
leucovorin calcium: Given IV or orally
|
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.
cisplatin: Given IV
dexrazoxane hydrochloride: Given IV
doxorubicin hydrochloride: Given IV
etoposide: Given IV
ifosfamide: Given IV
leucovorin calcium: Given IV or orally
|
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.
cisplatin: Given IV
dexrazoxane hydrochloride: Given IV
doxorubicin hydrochloride: Given IV
etoposide: Given IV
ifosfamide: Given IV
leucovorin calcium: Given IV or orally
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
1
|
1
|
|
Overall Study
Lack of Efficacy
|
5
|
1
|
2
|
4
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
1
|
0
|
Baseline Characteristics
Zoledronic Acid and Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Osteosarcoma
Baseline characteristics by cohort
| Measure |
Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid
n=6 Participants
(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
|
Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid
n=6 Participants
(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
|
Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid
n=6 Participants
(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
|
Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD
n=6 Participants
(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
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
11.5 years
n=5 Participants
|
15.5 years
n=7 Participants
|
14 years
n=5 Participants
|
14.5 years
n=4 Participants
|
13.5 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
5 participants
n=5 Participants
|
6 participants
n=4 Participants
|
20 participants
n=21 Participants
|
|
Region of Enrollment
Canada
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
4 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Enrollment through the first 12 weeks of therapy.Population: Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome
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.
Outcome measures
| Measure |
Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid
n=6 Participants
(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
|
Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid
n=6 Participants
(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
|
Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid
n=6 Participants
(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
|
Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD
n=6 Participants
(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
|
|---|---|---|---|---|
|
Limiting Toxicity
|
1 participants
|
1 participants
|
3 participants
|
2 participants
|
SECONDARY outcome
Timeframe: At definitive surgery planned for 12 weeks after the start of protocol therapy.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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from study enrollment to disease recurrence, death without disease progression, diagnosis of a second malignant neoplasm, assessed up to 5 yearsThe EFS and survival functions will be estimated by the Kaplan-Meier methodology.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: After week 13 to the end of protocol therapySecondary 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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At baseline and at weeks 13 and 36Blood will be collected for quantification of c-telopeptide and urine will be collected for quantification of n-telopeptide.
Outcome measures
Outcome data not reported
Adverse Events
Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid
n=6 participants at risk
(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
|
Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid
n=6 participants at risk
(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
|
Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid
n=6 participants at risk
(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
|
Chemotherapy and 2.3 mg/m2 Zoledronic Acid After MTD
n=6 participants at risk
(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
|
|---|---|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
50.0%
3/6
|
66.7%
4/6
|
33.3%
2/6
|
16.7%
1/6
|
|
Blood and lymphatic system disorders
Anemia
|
50.0%
3/6
|
66.7%
4/6
|
33.3%
2/6
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/6
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/6
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
1/6
|
16.7%
1/6
|
16.7%
1/6
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6
|
33.3%
2/6
|
0.00%
0/6
|
16.7%
1/6
|
|
General disorders
Edema limbs
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
|
Infections and infestations
Eye infection
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
33.3%
2/6
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Fracture
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Ear and labyrinth disorders
Hearing impaired
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
33.3%
2/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
33.3%
2/6
|
33.3%
2/6
|
100.0%
6/6
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hypokalemia
|
33.3%
2/6
|
33.3%
2/6
|
16.7%
1/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hyponatremia
|
16.7%
1/6
|
0.00%
0/6
|
50.0%
3/6
|
16.7%
1/6
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/6
|
50.0%
3/6
|
50.0%
3/6
|
16.7%
1/6
|
|
Vascular disorders
Hypotension
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Infections and infestations
Infections and infestations - Other, specify
|
33.3%
2/6
|
33.3%
2/6
|
33.3%
2/6
|
0.00%
0/6
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/6
|
16.7%
1/6
|
33.3%
2/6
|
16.7%
1/6
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/6
|
0.00%
0/6
|
50.0%
3/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
Neutrophil count decreased
|
50.0%
3/6
|
83.3%
5/6
|
66.7%
4/6
|
50.0%
3/6
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
16.7%
1/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
|
Investigations
Platelet count decreased
|
50.0%
3/6
|
66.7%
4/6
|
33.3%
2/6
|
16.7%
1/6
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
White blood cell decreased
|
66.7%
4/6
|
83.3%
5/6
|
33.3%
2/6
|
33.3%
2/6
|
Additional Information
Results Reporting Coordinator
Children's Oncology Group
Phone: 352-273-0558
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place