Trial Outcomes & Findings for Preventing Nephrotoxicity and Ototoxicity From Osteosarcoma Therapy (NCT NCT01848457)
NCT ID: NCT01848457
Last Updated: 2020-03-16
Results Overview
This measure describes the urinary biomarkers of AKI after each course of C throughout Cycles 1-2, compared to baseline (pre-infusion) values. Biomarkers of AKI, include: Kidney Injury Molecule-1 (KIM-1), and Neutrophil Gelatinase-Associated Lipocalin (NGAL).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
13 participants
Primary outcome timeframe
Pretreatment/Baseline, Day 2 of Cycles 1 & 2, Day 8 of Cycles 1 & 2
Results posted on
2020-03-16
Participant Flow
Participant milestones
| Measure |
Cycles 1 & 2: HDMTX 4h, PTZ+C; Then Cycles 3 & 4: HDTMX 12h, C
Cycles 1 and 2: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 12-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Cycles 1 & 2: HDMTX 4h, C; Then Cycles 3 & 4: HDTMX 12h, C+PTZ
Cycles 1 and 2: HDMTX administered as a 4-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Cycles 1 & 2: HDMTX 12h, PTZ+C; Then Cycles 3 & 4: HDTMX 4h, C
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 4-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Cycles 1 & 2: HDMTX 12h, C; Then Cycles 3 & 4: HDTMX 4h, C+PTZ
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
3
|
3
|
3
|
|
Overall Study
Baseline
|
4
|
3
|
3
|
3
|
|
Overall Study
Cycle 1
|
4
|
3
|
3
|
3
|
|
Overall Study
Cycle 2
|
3
|
3
|
3
|
3
|
|
Overall Study
Cycle 3
|
3
|
3
|
3
|
3
|
|
Overall Study
Cycle 4
|
3
|
3
|
3
|
3
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
3
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cycles 1 & 2: HDMTX 4h, PTZ+C; Then Cycles 3 & 4: HDTMX 12h, C
Cycles 1 and 2: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 12-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Cycles 1 & 2: HDMTX 4h, C; Then Cycles 3 & 4: HDTMX 12h, C+PTZ
Cycles 1 and 2: HDMTX administered as a 4-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Cycles 1 & 2: HDMTX 12h, PTZ+C; Then Cycles 3 & 4: HDTMX 4h, C
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 4-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Cycles 1 & 2: HDMTX 12h, C; Then Cycles 3 & 4: HDTMX 4h, C+PTZ
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
|---|---|---|---|---|
|
Overall Study
Death
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Preventing Nephrotoxicity and Ototoxicity From Osteosarcoma Therapy
Baseline characteristics by cohort
| Measure |
Arm 1
n=4 Participants
Cycles 1 and 2: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 12-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Arm 2
n=3 Participants
Cycles 1 and 2: HDMTX administered as a 4-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Arm 3
n=3 Participants
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 4-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Arm 4
n=3 Participants
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
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
|
|
Age, Continuous
|
14.3 years
n=5 Participants
|
10.3 years
n=7 Participants
|
8.3 years
n=5 Participants
|
10.7 years
n=4 Participants
|
11.4 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
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
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
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
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
3 participants
n=4 Participants
|
13 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Pretreatment/Baseline, Day 2 of Cycles 1 & 2, Day 8 of Cycles 1 & 2Population: The original treatment arms/groups are paired down by the arms that include PTZ in the CISplatin infusions, and the arms that do not include PTZ in the CISplatin infusions. This is a general comparison of the changes in AKI measurements when using the PTZ inhibitor, whether HDTMX is infused for 4 or 12 hours.
This measure describes the urinary biomarkers of AKI after each course of C throughout Cycles 1-2, compared to baseline (pre-infusion) values. Biomarkers of AKI, include: Kidney Injury Molecule-1 (KIM-1), and Neutrophil Gelatinase-Associated Lipocalin (NGAL).
Outcome measures
| Measure |
Treatments Arms 1 & 3 (Groups With PTZ in Cycles 1 & 2)
n=6 Participants
Arm 1 receives a 4-hour infusion of HDTX, and Arm 3 receives a 12-hour infusion of HDTMX, during Cycles 1 \& 2. Both arms also receive C and PTZ during Cycles 1 \& 2.
|
Treatments Arms 2 & 4 (Groups Without PTZ in Cycles 1 & 2)
n=6 Participants
Am 2 receives a 4-hour infusion of HDTMX, and Arm 4 receives a 12-hour infusion of HDTMX during Cycles 1 \& 2. Both arms also receive the C doses, but without PTZ.
|
Arm 3
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 4-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Arm 4
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
|---|---|---|---|---|
|
Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments
Day 1 Kim-1 (Pretreatment)
|
1.7 μg/g
Interval 0.5 to 5.9
|
1.7 μg/g
Interval 0.3 to 15.0
|
—
|
—
|
|
Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments
Day 2 Kim-1 (post 2 doses Cisplatin)
|
2.1 μg/g
Interval 0.2 to 182.0
|
3.3 μg/g
Interval 0.2 to 8.1
|
—
|
—
|
|
Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments
Day 8 Kim-1 (post HDTMX infusion)
|
4.1 μg/g
Interval 0.5 to 11.0
|
4.6 μg/g
Interval 0.4 to 11.0
|
—
|
—
|
|
Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments
Day 1 NGAL (Pretreatment)
|
18 μg/g
Interval 2.0 to 900.0
|
10 μg/g
Interval 2.9 to 165.0
|
—
|
—
|
|
Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments
Day 2 NGAL (post 2 doses Cisplatin)
|
27 μg/g
Interval 2.6 to 542.0
|
18 μg/g
Interval 1.1 to 209.0
|
—
|
—
|
|
Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments
Day 8 NGAL (post HDTMX infusion)
|
12 μg/g
Interval 2.2 to 1193.0
|
12 μg/g
Interval 1.6 to 841.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 1), Pre-operative (Month 2)Response of the primary tumor to the first two treatment cycles (Cycles 1 and 2) will be assessed by quantifying the change in tumor volume on MRI, after treatment (pre-operative) relative to the pre-treatment tumor volume. By using the log ratio of the tumor volume post-treatment, to the tumor volume pre-treatment. The larger the change, the more effective the treatment.
Outcome measures
| Measure |
Treatments Arms 1 & 3 (Groups With PTZ in Cycles 1 & 2)
n=9 Participants
Arm 1 receives a 4-hour infusion of HDTX, and Arm 3 receives a 12-hour infusion of HDTMX, during Cycles 1 \& 2. Both arms also receive C and PTZ during Cycles 1 \& 2.
|
Treatments Arms 2 & 4 (Groups Without PTZ in Cycles 1 & 2)
n=4 Participants
Am 2 receives a 4-hour infusion of HDTMX, and Arm 4 receives a 12-hour infusion of HDTMX during Cycles 1 \& 2. Both arms also receive the C doses, but without PTZ.
|
Arm 3
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 4-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Arm 4
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
|---|---|---|---|---|
|
Change in Tumor Volume
Complete Response to Chemotherapy
|
9 Participants
|
0 Participants
|
—
|
—
|
|
Change in Tumor Volume
Progressive Disease after Chemotherapy
|
0 Participants
|
4 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Pretreatment/Baseline), Day 8, and Day 22 of Cycles 1 & 2Urinary biomarkers of acute kidney injury (AKI) and glomerular filtration rate (GFR) estimated from serum cystatin C will be compared to standard measures of renal function (serum creatinine, urinalysis, estimated creatinine clearance, fractional excretion of Mg). Single reported values are averaged and reported with full ranges.
Outcome measures
| Measure |
Treatments Arms 1 & 3 (Groups With PTZ in Cycles 1 & 2)
n=6 Participants
Arm 1 receives a 4-hour infusion of HDTX, and Arm 3 receives a 12-hour infusion of HDTMX, during Cycles 1 \& 2. Both arms also receive C and PTZ during Cycles 1 \& 2.
|
Treatments Arms 2 & 4 (Groups Without PTZ in Cycles 1 & 2)
n=6 Participants
Am 2 receives a 4-hour infusion of HDTMX, and Arm 4 receives a 12-hour infusion of HDTMX during Cycles 1 \& 2. Both arms also receive the C doses, but without PTZ.
|
Arm 3
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 4-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Arm 4
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
|---|---|---|---|---|
|
Validating Urinary Biomarkers
Day 22 GFRcr
|
134 mL/min per 1.73m2
Interval 96.0 to 252.0
|
141 mL/min per 1.73m2
Interval 64.0 to 252.0
|
—
|
—
|
|
Validating Urinary Biomarkers
Day 1 GFRcysC (pretreatment)
|
126 mL/min per 1.73m2
Interval 89.0 to 169.0
|
120 mL/min per 1.73m2
Interval 87.0 to 180.0
|
—
|
—
|
|
Validating Urinary Biomarkers
Day 1 GFRcr (pretreatment)
|
131 mL/min per 1.73m2
Interval 96.0 to 252.0
|
132 mL/min per 1.73m2
Interval 95.0 to 252.0
|
—
|
—
|
|
Validating Urinary Biomarkers
Day 8 GFRcr
|
120 mL/min per 1.73m2
Interval 81.0 to 252.0
|
124 mL/min per 1.73m2
Interval 81.0 to 252.0
|
—
|
—
|
|
Validating Urinary Biomarkers
Day 8 GFRcysC
|
105 mL/min per 1.73m2
Interval 78.0 to 193.0
|
109 mL/min per 1.73m2
Interval 72.0 to 186.0
|
—
|
—
|
|
Validating Urinary Biomarkers
Day 22 GFRcysC
|
122 mL/min per 1.73m2
Interval 94.0 to 160.0
|
125 mL/min per 1.73m2
Interval 77.0 to 176.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Pretreatment (biopsy) at baseline and postoperative (in between cycle 2 and cycle 3)Population: The study was completed early and biopsy specimens were not submitted for tissue microarray analysis for any patients.
Tissue microarray will be constructed from biopsy specimens, primary resection and resected metastatic tumors to evaluate the expression of proteins that are responsible for resistance to the drugs in the MAP regimen and to assess expression of proteins that are targeted by new anticancer drugs under development for childhood cancers.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pretreatment/Baseline, Cycle 3Serum BSAP will be longitudinally evaluated as a potential biomarker for osteosarcoma
Outcome measures
| Measure |
Treatments Arms 1 & 3 (Groups With PTZ in Cycles 1 & 2)
n=2 Participants
Arm 1 receives a 4-hour infusion of HDTX, and Arm 3 receives a 12-hour infusion of HDTMX, during Cycles 1 \& 2. Both arms also receive C and PTZ during Cycles 1 \& 2.
|
Treatments Arms 2 & 4 (Groups Without PTZ in Cycles 1 & 2)
n=3 Participants
Am 2 receives a 4-hour infusion of HDTMX, and Arm 4 receives a 12-hour infusion of HDTMX during Cycles 1 \& 2. Both arms also receive the C doses, but without PTZ.
|
Arm 3
n=3 Participants
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 4-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Arm 4
n=3 Participants
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
|---|---|---|---|---|
|
Bone Specific Alkaline Phosphatase (BSAP)
Pretreatment (baseline)
|
197.1 U/L
Interval 40.2 to 354.0
|
265 U/L
Interval 106.0 to 557.0
|
169.67 U/L
Interval 111.0 to 265.0
|
179.63 U/L
Interval 66.7 to 398.0
|
|
Bone Specific Alkaline Phosphatase (BSAP)
Cycle 3
|
73.05 U/L
Interval 46.1 to 100.0
|
106.87 U/L
Interval 18.6 to 193.0
|
71.2 U/L
Interval 26.1 to 137.0
|
76.1 U/L
Interval 44.6 to 125.0
|
SECONDARY outcome
Timeframe: Prior to each cycle (Day 1 of cycles 1-6) and end of therapy (at the end of cycle 6)Population: The nutritional information collected was not able to be reported, due to the metabolized nature of the data. The data points were not able to be included, because they were not able to be read.
Nutritional status (weight, arm circumference, skin fold thickness, pre-albumin) will be throughout the course of treatment
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, Cycle 2, Surgery, Cycle 3, Cycle 4, Cycle 5, Cycle 6, and End of TherapyPopulation: The number analyzed differed between rows and from the overall number of analyzed subjects, because not all subjects completed PROS questionnaires during study visits due to time limitations, and/or activities of the study procedures.
PROS survey measures quality of life for pediatric oncology patients, in 17 scaled questions. Each question scaled 0-4 (0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Often, 4 = Almost Always). The higher the final sum of the questions, the lower the quality of life/more severe the side effects of oncology treatment. Total scores can range between 0 = highest quality of life, and 100 = experiencing most severe side effects of oncology treatment/worst quality of life experience.
Outcome measures
| Measure |
Treatments Arms 1 & 3 (Groups With PTZ in Cycles 1 & 2)
n=8 Participants
Arm 1 receives a 4-hour infusion of HDTX, and Arm 3 receives a 12-hour infusion of HDTMX, during Cycles 1 \& 2. Both arms also receive C and PTZ during Cycles 1 \& 2.
|
Treatments Arms 2 & 4 (Groups Without PTZ in Cycles 1 & 2)
Am 2 receives a 4-hour infusion of HDTMX, and Arm 4 receives a 12-hour infusion of HDTMX during Cycles 1 \& 2. Both arms also receive the C doses, but without PTZ.
|
Arm 3
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 4-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Arm 4
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
|---|---|---|---|---|
|
Patient Reported Outcome Survey (PROS)
Baseline
|
23 score on a scale
Interval 16.0 to 43.0
|
—
|
—
|
—
|
|
Patient Reported Outcome Survey (PROS)
Cycle 2
|
30 score on a scale
Interval 17.0 to 46.0
|
—
|
—
|
—
|
|
Patient Reported Outcome Survey (PROS)
Surgery
|
22 score on a scale
Interval 10.0 to 30.0
|
—
|
—
|
—
|
|
Patient Reported Outcome Survey (PROS)
Cycle 3
|
24 score on a scale
Interval 4.0 to 34.0
|
—
|
—
|
—
|
|
Patient Reported Outcome Survey (PROS)
Cycle 4
|
24 score on a scale
Interval 7.0 to 42.0
|
—
|
—
|
—
|
|
Patient Reported Outcome Survey (PROS)
Cycle 5
|
19 score on a scale
Interval 9.0 to 32.0
|
—
|
—
|
—
|
|
Patient Reported Outcome Survey (PROS)
Cycle 6
|
20 score on a scale
Interval 5.0 to 32.0
|
—
|
—
|
—
|
|
Patient Reported Outcome Survey (PROS)
End of Therapy
|
17 score on a scale
Interval 12.0 to 23.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Week 1), Day 1 of Cycle 1 (Week 1), Day 1 of Cycle 2(Week 6), Day 1 of Cycle 3(Week 11), Day 1 of Cycle 4 (Week 16), and end of therapy/after the end of cycle 6 (Day 28 of cycle 6, Week 28)Average hearing level (HL) threshold in decibels (dB) over the frequency range of 4,000-8,000 hertz (Hz) will be derived separately for each ear from audiograms performed before each dose of cisplatin.
Outcome measures
| Measure |
Treatments Arms 1 & 3 (Groups With PTZ in Cycles 1 & 2)
n=7 Participants
Arm 1 receives a 4-hour infusion of HDTX, and Arm 3 receives a 12-hour infusion of HDTMX, during Cycles 1 \& 2. Both arms also receive C and PTZ during Cycles 1 \& 2.
|
Treatments Arms 2 & 4 (Groups Without PTZ in Cycles 1 & 2)
n=5 Participants
Am 2 receives a 4-hour infusion of HDTMX, and Arm 4 receives a 12-hour infusion of HDTMX during Cycles 1 \& 2. Both arms also receive the C doses, but without PTZ.
|
Arm 3
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and pantoprazole is administered with cisplatin Cycles 3 and 4: HDMTX administered as a 4-hour infusion and cisplatin is administered alone
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
Arm 4
Cycles 1 and 2: HDMTX administered as a 12-hour infusion and cisplatin is administered alone Cycles 3 and 4: HDMTX administered as a 4-hour infusion and pantoprazole is administered with cisplatin
Pantoprazole: 0.3 mg/kg IV over 15 min immediately prior to cisplatin as a loading dose on days 1 \& 2 followed by 1.3 mg/kg IV infused over 4 h concurrent with the 4 h cisplatin infusion on days 1 \& 2 of treatment Cycles 1 \& 2 (Treatment Arms 1, 3) OR Cycles 3 \& 4 (Treatment Arms 2, 4)
High-dose methotrexate infusion duration: High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours
|
|---|---|---|---|---|
|
Ototoxicity
Baseline Right Ear
|
3.6 decibels
Interval 0.0 to 8.3
|
3.8 decibels
Interval 1.7 to 6.7
|
—
|
—
|
|
Ototoxicity
Baseline Left Ear
|
3.3 decibels
Interval 0.0 to 5.0
|
5.4 decibels
Interval 1.7 to 10.0
|
—
|
—
|
|
Ototoxicity
End of Therapy Right Ear
|
34.6 decibels
Interval 11.7 to 58.3
|
26.7 decibels
Interval 10.0 to 41.7
|
—
|
—
|
|
Ototoxicity
End of Therapy Left Ear
|
35.0 decibels
Interval 23.3 to 58.3
|
26.7 decibels
Interval 10.0 to 41.7
|
—
|
—
|
Adverse Events
Arm 1
Serious events: 0 serious events
Other events: 0 other events
Deaths: 1 deaths
Arm 2
Serious events: 0 serious events
Other events: 0 other events
Deaths: 1 deaths
Arm 3
Serious events: 0 serious events
Other events: 0 other events
Deaths: 1 deaths
Arm 4
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place