OsteosarcomaPhase 2NCT01848457

Preventing Nephrotoxicity and Ototoxicity From Osteosarcoma Therapy

A Phase 2 study testing Pantoprazole and High-dose methotrexate infusion duration in people with Osteosarcoma and Nephrotoxicity, run by Children's Hospital of Philadelphia at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages Up to 30 years
Conditions the study is for: Osteosarcoma, Nephrotoxicity, Ototoxicity
What is being tested?: Pantoprazole and High-dose methotrexate infusion duration
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 1 siteUnited States
Study dates: Apr 2013to 1 Oct 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 30 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

<30 years of age
histological diagnosis of high-grade osteosarcoma
Extremity or central axis (including craniofacial) primary tumor; localized or metastatic
No prior chemotherapy or radiation therapy for osteosarcoma. Subjects who develop osteosarcoma as a second cancer are eligible if they have not previously received cisplatin, doxorubicin or other anthracyclines, or MTX
Serum creatinine at or below the upper limit of normal (ULN) for age and gender
Shortening fraction on echocardiogram >28%
Hearing level threshold ≤25 dB at all frequencies in both ears to be evaluable for evaluation of pantoprazole's effect on cisplatin ototoxicity. Patients with hearing loss can be enrolled but will not be evaluable for ototoxicity objective.
Absolute neutrophil count >1,000/microliter(mcL) and platelet count >100,000/mcL

Who cannot join

Receiving H2 antagonists (cimetidine, ranitidine, famotidine, nizatidine) or proton pump inhibitors (lansoprazole, omeprazole, pantoprazole, esomeprazole, rabeprazole, dexlansoprazole) AND unable to hold the drug for 24 h prior to and 24 h after each cisplatin course on cycles 1-4.
Pregnant or breastfeeding
Unable to cooperate with research procedures

Trial locations and contacts

1 site in 1 country.

United States1 site

Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Pilot Study to Prevent Nephrotoxicity of High-Dose Methotrexate by Prolonging the Infusion Duration and Prevent Nephrotoxicity and Ototoxicity of Cisplatin With Pantoprazole in Children, Adolescents and Young Adults With Osteosarcoma

Osteosarcoma is the most common type of bone cancer in children, adolescents and young adults. Treatment with surgery and a combination of three conventional chemotherapy drugs can cure nearly two-thirds patients with osteosarcoma, but the treatment can also cause irreversible damage to the kidneys and cause permanent hearing loss. The purpose of this study is to evaluate new approaches to prevent these side effects without interfering with the beneficial effects of the chemotherapy drugs on the cancer by using our knowledge of how the drugs damage the kidney and cochlear hair cells in the ear to selectively block these side effects. Preventing these side effects without interfering with the anti-cancer effect of the drugs will improve the outcome in survivors and may also improve the effectiveness of the chemotherapy regimen by preventing treatment delays and dose reductions that are often caused by the side effects. Patients will be carefully monitored to ensure that the new interventions do not adversely affect response to the treatment and do not increase the other side effects of the chemotherapy. Specifically, we will monitor the nutritional status of the patients closely and ask patients to complete a survey describing the side effects after each treatment cycle. We will also collect a small sample of cancer tissue at the time of biopsy and surgery from each patient on this study for testing to determine new classes of anti-cancer drugs currently under development may have a role in treating osteosarcoma. If effective, these new approaches to prevent kidney damage and hearing loss will be applicable in other types of cancers treated with the same chemotherapy drugs.

Read the detailed description

Current osteosarcoma treatment regimens include cisplatin and high-dose methotrexate (HDMTX), which are nephrotoxic and ototoxic, and the damage to kidneys and cochlear hair cells may be irreversible. Preventing these toxicities will improve the outcome in long-term survivors and may also prevent short-term treatment delays and dose reductions that can compromise the efficacy of the treatment regimen and allow for administration of higher cumulative doses of cisplatin. This pilot study evaluates pharmacologically-based approaches to prevent the nephrotoxic effect of HDMTX by prolonging the infusion duration and thereby lowering the risk of drug precipitation in renal tubules; and to selectively block the uptake of cisplatin into renal tubular cells and cochlear hair cells by inhibiting the organic cation transporter 2 (OCT2) with the proton pump inhibitor (PPI), pantoprazole. Participants with previously untreated biopsy-proven, localized or metastatic osteosarcoma will receive six cycles of the standard Methotrexate, Adriamycin (doxorubicin),cisplatin (MAP) chemotherapy regimen, which includes high-dose methotrexate, doxorubicin and cisplatin. The first 2 cycles are administered neoadjuvantly followed by surgery to remove the primary tumor, when feasible.

A novel randomized, crossover, 2 x 2 factorial clinical trial design allows all patients to receive the new interventions to prevent toxicity and to serve as their own controls. New, sensitive urinary biomarkers of acute kidney injury serve as primary endpoints for evaluating treatment-related renal damage. Ototoxicity will be monitored using audiograms. The effect of these interventions on tumor response (radiographic and histologic) and toxicity (including a patient reported outcome survey and nutritional status) will be closely monitored. Other secondary objectives include evaluating bone-specific alkaline phosphatase as a biomarker of tumor burden and constructing a tissue microarray to evaluate expression of proteins that are responsible for resistance to the current drugs used to treat osteosarcoma and assess expression of proteins that are targeted by new anticancer drugs under development for childhood cancers.

Conditions: Osteosarcoma, Nephrotoxicity, Ototoxicity
Being tested: Pantoprazole, High-dose methotrexate infusion duration
Keywords: Osteosarcoma, Cancer, Nephrotoxicity, Ototoxicity, Cisplatin, High-dose methotrexate, Biomarkers, Patient reported outcomes
Medical subject headings: Osteosarcoma, Ototoxicity, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PantoprazoleDrug
Also called Protonix IV
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 durationDrug
Also called Otrexup (PF), Xatmep, Trexall
High-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours

Study groups in NCT01848457
Study group	Role	What they receive
Cycles 1 & 2: HDMTX 4 h, PTZ+C; Cycles 3 & 4: HDMTX 12 h, C	Experimental	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 Receives: Drug: Pantoprazole; Drug: High-dose methotrexate infusion duration
Cycles 1 & 2: HDMTX 4 h, C; Cycles 3 & 4: HDMTX 12 h, PTZ + C	Experimental	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 Receives: Drug: Pantoprazole; Drug: High-dose methotrexate infusion duration
Cycles 1 & 2: HDMTX 12 h, PTZ+C; Cycles 3 & 4: HDMTX 4 h, C	Experimental	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 Receives: Drug: Pantoprazole; Drug: High-dose methotrexate infusion duration
Cycles 1 & 2: HDMTX 12 h, C; Cycles 3 & 4: HDMTX 4 h, C + PTZ	Experimental	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 Receives: Drug: Pantoprazole; Drug: High-dose methotrexate infusion duration

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments
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).
Measured: Pretreatment/Baseline, Day 2 of Cycles 1 & 2, Day 8 of Cycles 1 & 2

Secondary outcomes (7)

Change in Tumor Volume
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.
Measured: Baseline (Week 1), Pre-operative (Month 2)
Validating Urinary Biomarkers
Urinary 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.
Measured: Day 1 (Pretreatment/Baseline), Day 8, and Day 22 of Cycles 1 & 2
Tissue Microarray
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.
Measured: Pretreatment (biopsy) at baseline and postoperative (in between cycle 2 and cycle 3)
Bone Specific Alkaline Phosphatase (BSAP)
Serum BSAP will be longitudinally evaluated as a potential biomarker for osteosarcoma
Measured: Pretreatment/Baseline, Cycle 3
Nutritional Status
Nutritional status (weight, arm circumference, skin fold thickness, pre-albumin) will be throughout the course of treatment
Measured: Prior to each cycle (Day 1 of cycles 1-6) and end of therapy (at the end of cycle 6)
Patient Reported Outcome Survey (PROS)
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.
Measured: Baseline, Cycle 2, Surgery, Cycle 3, Cycle 4, Cycle 5, Cycle 6, and End of Therapy
Ototoxicity
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.
Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 20131 Oct 2016

First posted7 May 2013 (estimated)
Study startApr 2013
Primary completion4 Jan 2016
Study completion1 Oct 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for OsteosarcomaStudies of the same condition, open and under way.
More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01848457
Sponsor's protocol ID: 13-009967
Other IDs: CHP12ST051 OS Pilot
Status last verified: Mar 2020
First submitted: 29 Apr 2013
Last updated: 16 Mar 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Fox E, Busch C, DeBernardo A, Segers B, Gottschalk J, Womer R, Balamuth N, Bagatell R, Balis F. A pharmacologically-based approach to high dose methotrexate administration to investigate nephrotoxicity and acute kidney injury biomarkers in children and adolescents with newly diagnosed osteosarcoma. Cancer Chemother Pharmacol. 2021 Jun;87(6):807-815. doi: 10.1007/s00280-021-04248-8. Epub 2021 Mar 7.
PubMed 33677616
Fox E, Levin K, Zhu Y, Segers B, Balamuth N, Womer R, Bagatell R, Balis F. Pantoprazole, an Inhibitor of the Organic Cation Transporter 2, Does Not Ameliorate Cisplatin-Related Ototoxicity or Nephrotoxicity in Children and Adolescents with Newly Diagnosed Osteosarcoma Treated with Methotrexate, Doxorubicin, and Cisplatin. Oncologist. 2018 Jul;23(7):762-e79. doi: 10.1634/theoncologist.2018-0037. Epub 2018 Feb 14.
PubMed 29445029

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Osteosarcoma trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study to Prevent Nephrotoxicity of High-Dose Methotrexate by Prolonging the Infusion Duration and Prevent Nephrotoxicity and Ototoxicity of Cisplatin With Pantoprazole in Children, Adolescents and Young Adults With Osteosarcoma
ClinicalTrials.gov ID: NCT01848457
Acronym / sponsor ID: 13-009967
Conditions: Osteosarcoma, Nephrotoxicity, Ototoxicity
Keywords: Osteosarcoma, Cancer, Nephrotoxicity, Ototoxicity, Cisplatin, High-dose methotrexate, Biomarkers, Patient reported outcomes
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Children's Hospital of PhiladelphiaUniversity, hospital or other
Collaborators: Gateway for Cancer Research
Study start: Apr 2013 (actual)
Primary completion: 4 Jan 2016 (actual)
Study completion: 1 Oct 2016 (actual)
First posted: 7 May 2013 (estimated)
Results: Posted 16 Mar 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Cycles 1 & 2: HDMTX 4 h, PTZ+C; Cycles 3 & 4: HDMTX 12 h, C	Experimental	Drug: Pantoprazole, Drug: High-dose methotrexate infusion durationCycles 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
Cycles 1 & 2: HDMTX 4 h, C; Cycles 3 & 4: HDMTX 12 h, PTZ + C	Experimental	Drug: Pantoprazole, Drug: High-dose methotrexate infusion durationCycles 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
Cycles 1 & 2: HDMTX 12 h, PTZ+C; Cycles 3 & 4: HDMTX 4 h, C	Experimental	Drug: Pantoprazole, Drug: High-dose methotrexate infusion durationCycles 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
Cycles 1 & 2: HDMTX 12 h, C; Cycles 3 & 4: HDMTX 4 h, C + PTZ	Experimental	Drug: Pantoprazole, Drug: High-dose methotrexate infusion durationCycles 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

Who may qualify

Ages: Up to 30 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (8 listed)

<30 years of age
histological diagnosis of high-grade osteosarcoma
Extremity or central axis (including craniofacial) primary tumor; localized or metastatic
No prior chemotherapy or radiation therapy for osteosarcoma. Subjects who develop osteosarcoma as a second cancer are eligible if they have not previously received cisplatin, doxorubicin or other anthracyclines, or MTX
Serum creatinine at or below the upper limit of normal (ULN) for age and gender

Key exclusion criteria (3 listed)

Receiving H2 antagonists (cimetidine, ranitidine, famotidine, nizatidine) or proton pump inhibitors (lansoprazole, omeprazole, pantoprazole, esomeprazole, rabeprazole, dexlansoprazole) AND unable to hold the drug for 24 h prior to and 24 h after each cisplatin course on cycles 1-4.
Pregnant or breastfeeding
Unable to cooperate with research procedures

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PantoprazoleAlso: Protonix IV0.3 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)	Drug	Cycles 1 & 2: HDMTX 12 h, C; Cycles 3 & 4: HDMTX 4 h, C + PTZ, Cycles 1 & 2: HDMTX 12 h, PTZ+C; Cycles 3 & 4: HDMTX 4 h, C, Cycles 1 & 2: HDMTX 4 h, C; Cycles 3 & 4: HDMTX 12 h, PTZ + C, Cycles 1 & 2: HDMTX 4 h, PTZ+C; Cycles 3 & 4: HDMTX 12 h, C
High-dose methotrexate infusion durationAlso: Otrexup (PF), Xatmep, TrexallHigh-dose methotrexate (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours	Drug	Cycles 1 & 2: HDMTX 12 h, C; Cycles 3 & 4: HDMTX 4 h, C + PTZ, Cycles 1 & 2: HDMTX 12 h, PTZ+C; Cycles 3 & 4: HDMTX 4 h, C, Cycles 1 & 2: HDMTX 4 h, C; Cycles 3 & 4: HDMTX 12 h, PTZ + C, Cycles 1 & 2: HDMTX 4 h, PTZ+C; Cycles 3 & 4: HDMTX 12 h, C

Primary outcome

Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments
Time frame: Pretreatment/Baseline, Day 2 of Cycles 1 & 2, Day 8 of Cycles 1 & 2
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).

7 secondary outcomes

Change in Tumor Volume
Time frame: Baseline (Week 1), Pre-operative (Month 2)
Validating Urinary Biomarkers
Time frame: Day 1 (Pretreatment/Baseline), Day 8, and Day 22 of Cycles 1 & 2
Tissue Microarray
Time frame: Pretreatment (biopsy) at baseline and postoperative (in between cycle 2 and cycle 3)
Bone Specific Alkaline Phosphatase (BSAP)
Time frame: Pretreatment/Baseline, Cycle 3
Nutritional Status
Time frame: Prior to each cycle (Day 1 of cycles 1-6) and end of therapy (at the end of cycle 6)
Patient Reported Outcome Survey (PROS)
Time frame: Baseline, Cycle 2, Surgery, Cycle 3, Cycle 4, Cycle 5, Cycle 6, and End of Therapy
Ototoxicity
Time frame: 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)

Results and safety

Results posted to the registry on 16 Mar 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cycles 1 & 2: HDMTX 4h, PTZ+C; Then Cycles 3 & 4: HDTMX 12h, C	4	3
Cycles 1 & 2: HDMTX 4h, C; Then Cycles 3 & 4: HDTMX 12h, C+PTZ	3	3
Cycles 1 & 2: HDMTX 12h, PTZ+C; Then Cycles 3 & 4: HDTMX 4h, C	3	3
Cycles 1 & 2: HDMTX 12h, C; Then Cycles 3 & 4: HDTMX 4h, C+PTZ	3	3

Primary outcome: Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments

Time frame: Pretreatment/Baseline, Day 2 of Cycles 1 & 2, Day 8 of Cycles 1 & 2. Median (Full Range). Unit: μg/g

Measure	Treatments Arms 1 & 3 (Groups With PTZ in Cycles 1 & 2) n = 6	Treatments Arms 2 & 4 (Groups Without PTZ in Cycles 1 & 2) n = 6
Day 1 Kim-1 (Pretreatment)	1.7 (0.5 to 5.9)	1.7 (0.3 to 15)
Day 2 Kim-1 (post 2 doses Cisplatin)	2.1 (0.2 to 182)	3.3 (0.2 to 8.1)
Day 8 Kim-1 (post HDTMX infusion)	4.1 (0.5 to 11)	4.6 (0.4 to 11)
Day 1 NGAL (Pretreatment)	18 (2 to 900)	10 (2.9 to 165)
Day 2 NGAL (post 2 doses Cisplatin)	27 (2.6 to 542)	18 (1.1 to 209)
Day 8 NGAL (post HDTMX infusion)	12 (2.2 to 1193)	12 (1.6 to 841)

Population analysed: 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.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events are tracked from the time of the first subject's enrollment, until completion of study therapy of the last enrolled subject, spanning 3.5 years. Each treatment cycle is 4-5 weeks, and there are 6 treatment cycles per subject (24-30 weeks of treatment cycles). In addition, surgery recovery after Cycle 2 is 1-2 weeks. Each fully evaluable subject participated in the study 25-32 weeks (6-8 months).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm 1	0 of 4 (0%)	0 of 4 (0%)	1 of 4
Arm 2	0 of 3 (0%)	0 of 3 (0%)	1 of 3
Arm 3	0 of 3 (0%)	0 of 3 (0%)	1 of 3
Arm 4	0 of 3 (0%)	0 of 3 (0%)	0 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33677616Fox E, Busch C, DeBernardo A, Segers B, Gottschalk J, Womer R, Balamuth N, Bagatell R, Balis F. A pharmacologically-based approach to high dose methotrexate administration to investigate nephrotoxicity and acute kidney injury biomarkers in children and adolescents with newly diagnosed osteosarcoma. Cancer Chemother Pharmacol. 2021 Jun;87(6):807-815. doi: 10.1007/s00280-021-04248-8. Epub 2021 Mar 7.
Derived from this study: PubMed 29445029Fox E, Levin K, Zhu Y, Segers B, Balamuth N, Womer R, Bagatell R, Balis F. Pantoprazole, an Inhibitor of the Organic Cation Transporter 2, Does Not Ameliorate Cisplatin-Related Ototoxicity or Nephrotoxicity in Children and Adolescents with Newly Diagnosed Osteosarcoma Treated with Methotrexate, Doxorubicin, and Cisplatin. Oncologist. 2018 Jul;23(7):762-e79. doi: 10.1634/theoncologist.2018-0037. Epub 2018 Feb 14.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Frank M Balis, MD principal investigator

Children's Hospital of Philadelphia

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments (time frame: Pretreatment/Baseline, Day 2 of Cycles 1 & 2, Day 8 of Cycles 1 & 2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01848457, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2020.