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Phase 2 N=13 Randomized Supportive Care

Preventing Nephrotoxicity and Ototoxicity From Osteosarcoma Therapy

Osteosarcoma · Nephrotoxicity · Ototoxicity

Enrolled (actual)
13
Serious AEs
0.0%
Results posted
Mar 2020
Primary outcome: Primary: Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments — 1.7; 1.7; 2.1; 3.3 μg/g

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Pantoprazole (Drug); High-dose methotrexate infusion duration (Drug)
Age
Pediatric, Adult
Sex
All
Sponsor
Children's Hospital of Philadelphia
Primary completion
Jan 2016

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Urinary Biomarkers of Acute Kidney Injury (AKI) Between Pre-Treatment (Baseline), After CISplatin (C) Treatments, and After HDTMX Treatments
1.7; 1.7; 2.1; 3.3; 4.1; 4.6
SECONDARY
Change in Tumor Volume
9; 0; 0; 4
SECONDARY
Validating Urinary Biomarkers
131; 132; 120; 124; 134; 141
SECONDARY
Tissue Microarray
SECONDARY
Bone Specific Alkaline Phosphatase (BSAP)
197.1; 265; 169.67; 179.63; 73.05; 106.87
SECONDARY
Nutritional Status
SECONDARY
Patient Reported Outcome Survey (PROS)
23; 30; 22; 24; 24; 19
SECONDARY
Ototoxicity
3.6; 3.8; 3.3; 5.4; 34.6; 26.7

Summary

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.

Eligibility Criteria

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01848457). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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