Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Gastrointestinal Agents

Docetaxel

Prednisone

Pantoprazole

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Enzyme Inhibitors

The main objectives of this trial are:

1. To assess the activity and safety of pantoprazole and docetaxel (with prednisone) in men with metastatic CRPC who have not received prior chemotherapy.
2. To evaluate archival prostate cancer tissue of men included in the clinical trial for evidence of autophagy using IHC for LC3B, ATG5, p62 as well as ERG.
3. To evaluate pharmacokinetic interactions of pantoprazole with docetaxel.

Pantoprazole and Docetaxel for Men With Metastatic Castration-Resistant Prostate Cancer

Pantoprazole and Docetaxel for Men With Metastatic Castration-Resistant Prostate Cancer - a Single Arm Phase II Clinical Trial With a Predefined Reference Group (PANDORA)

The primary endpoint is met if PSA falls to ≤50% of baseline, maintained for ≥3 weeks.

University Health Network, Toronto

Ear, Nose, and Throat Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Skin and Connective Tissue Diseases

Rare Diseases

Osteosarcoma

Ototoxicity

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Ear Diseases

Otorhinolaryngologic Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Soft Tissue Sarcoma

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Methotrexate

Cisplatin

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

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

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

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

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

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 (12 g/sq m, maximum dose 20 g) will be infused over 4 hours or 12 hours

High-dose methotrexate infusion duration

Frank M Balis, MD

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.

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.

Preventing Nephrotoxicity and Ototoxicity From Osteosarcoma Therapy

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

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).

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.

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.

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.

Serum BSAP will be longitudinally evaluated as a potential biomarker for osteosarcoma

Nutritional status (weight, arm circumference, skin fold thickness, pre-albumin) will be throughout the course of treatment

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.

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.

Gateway for Cancer Research

Children's Hospital of Philadelphia

Adverse events were tracked according to arms/groups of studies, and the cycles at which they occured for each arm/group. Given the nature of how the interventions were implemented, separating each treatment or intervention would not account for the cause of the adverse event, nor identify the time at which the adverse event occured. In order to be consistent, adverse events are reported according to the arm in which they occured.

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 1

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 2

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 3

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

Arm 4

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Frank Balis, MD

Day 1 Kim-1 (Pretreatment)

Day 2 Kim-1 (post 2 doses Cisplatin)

Day 8 Kim-1 (post HDTMX infusion)

Day 1 NGAL (Pretreatment)

Day 2 NGAL (post 2 doses Cisplatin)

Day 8 NGAL (post HDTMX infusion)

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 1 & 3 (Groups With 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.

Treatments Arms 2 & 4 (Groups Without PTZ in Cycles 1 & 2)

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.

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

Complete Response to Chemotherapy

Progressive Disease after Chemotherapy

Localized Disease at Baseline

Metastatic Disease at Baseline

Change in Tumor Volume

Day 1 GFRcr (pretreatment)

Day 8 GFRcr

Day 22 GFRcr

Day 1 GFRcysC (pretreatment)

Day 8 GFRcysC

Day 22 GFRcysC

Treatment Arms 1, 3 (w/ Pantoprazole)

Treatment Arms 2, 4 (w/o Pantoprazole)

Validating Urinary Biomarkers

The study was completed early and biopsy specimens were not submitted for tissue microarray analysis for any patients.

Tissue Microarray

Pretreatment (baseline)

Cycle 3

Bone Specific Alkaline Phosphatase (BSAP)

Individual Subjects

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

Baseline

Cycle 2

Surgery

Cycle 4

Cycle 5

Cycle 6

End of Therapy

All participants in the study, regardless of which arm or order they were randomized to receive the study treatment.

All Study Participants (Arms 1-4)

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.

Patient Reported Outcome Survey (PROS)

Baseline Right Ear

Baseline Left Ear

End of Therapy Right Ear

End of Therapy Left Ear

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

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

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

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

Overall Study

Digestive System Diseases

Gland and Hormone Related Diseases

Syndrome

Gastrinoma

Zollinger-Ellison Syndrome

Carcinoma

Carcinoma, Islet Cell

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Paraneoplastic Syndromes

Ulcer

Peptic Ulcer

Duodenal Diseases

Intestinal Diseases

Stomach Diseases

Pancreatic Cancer

Omeprazole

Patients with Zollinger-Ellison Syndrome suffer from ulcers of the upper gastrointestinal tract, higher than normal levels of gastric acid, and tumors of the pancreas known as non-beta islet cell tumors. Patients with Zollinger-Ellison Syndrome require continuous control of their gastric acid secretion. If gastric acid levels are permitted to rise higher than normal, patients may develop severe ulcers and other complications.

This study will attempt to determine the effectiveness of Omeprazole (Prilosec) in the treatment of patients with Zollinger-Ellison Syndrome. Omeprazole is a drug that functions to decrease the amount of gastric acid secreted.

Patients for this study will be selected based on a previous diagnosis of Zollinger-Ellison Syndrome and/or idiopathic (unknown cause) high levels of gastric acid secretion. The patients will undergo an evaluation including history and physical examination as well as necessary laboratory tests. The proper dose of Omeprazole will then be determined in each patient . The proper dose of Omeprazole is considered the minimum amount of omeprazole required to lower gastric acid to a safe level.

Every year patients participating in this study will undergo a physical examination and history. They will be questioned about symptoms associated with Zollinger-Ellison Syndrome. Gastric acid levels will be taken and evaluated and patients will undergo an upper gastrointestinal endoscopy.

The effectiveness of the treatment will be measured by a clinical history to determine the control of symptoms due to high levels of gastric acid secretion.

Patients with Zollinger-Ellison syndrome require continuous control of their gastric acid secretion or else severe complications of peptic ulcer disease will occur. This study investigates the long-term efficacy of the oral gastric acid antisecretory drug, Omeprazole, which functions as a H+ - K+ ATPase inhibitor. Long-term safety will also be investigated. Also investigated is the ability of the parenteral H+-K+ ATPase inhibitor, pantoprazole to control acid secretion short-term, when oral Omeprazole cannot be used.

In this study the proper maintenance dose of oral Omeprazole will be determined in each patient by determining the minimal dose of drug that reduces acid secretion to safe levels. Patients will be examined at least annually for evidence of continued efficacy and safety. Efficacy will be assessed by clinical history to assess control of symptoms due to gastric acid hypersecretion, measurements of gastric acid secretion while on Omeprazole to determine continued effectiveness of the drug and upper gastrointestinal endoscopy to assess changes in the gastrointestinal mucosa. Safety will be determined by assessing clinical and laboratory parameters such as changes in hematologic or clinical chemistry parameters. Possible drug induced changes in the gastric mucosa will be assessed by gastric biopsies.

With intravenous pantoprazole the ability of the recommended dose of 80 mg three times a day to control acid secretion will be investigated and if this fails, 80 mg four times a day will be assessed.

The Use of Oral Omeprazole and Intravenous Pantoprazole in Patients With Hypersecretion of Gastric Acid

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Cholangiocarcinoma

Neuroendocrine Tumors

Pancreatitis

Duodenal Neoplasms

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Intestinal Neoplasms

Bile Duct Cancer

Neuroendocrine Tumor

Neuroepithelioma

-Visually equivalent placebo once daily from postoperative day 1 and continued for 10 doses or until the day of discharge (whichever is earlier).

-Pantoprazole once daily from postoperative day 1 and continued for 10 doses or until the day of discharge (whichever is earlier).

Placebo capsules contain pharmaceutical-grade lactose monohydrate NF, a naturally occurring disaccharide of galactose bound to glucose.

Placebo

Natash Leigh, M.D.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pantoprazole and Docetaxel for Men With Metastatic Castration-Resistant Prostate Cancer	NCT01748500	Prostate Cancer	Pantoprazole	18 Years -	University Health Network, Toronto
Preventing Nephrotoxicity and Ototoxicity From Osteosarcoma Therapy	NCT01848457	Osteosarcoma Nephrotoxicity Ototoxicity	Pantoprazole High-dose metho...	- 30 Years	Children's Hospital of Philadelphia
The Use of Oral Omeprazole and Intravenous Pantoprazole in Patients With Hypersecretion of Gastric Acid	NCT00001191	Gastrinoma Zollinger Ellis...	Pantoprazole Omeprazole	18 Years -	National Institutes of Health Clinical Center (CC)
Preventing Nephrotoxicity and Ototoxicity From Osteosarcoma Therapy	NCT01848457	Osteosarcoma Nephrotoxicity Ototoxicity	Pantoprazole High-dose metho...	- 30 Years	Children's Hospital of Philadelphia
Role of Proton Pump Inhibitors on the Postoperative Course Following Pancreaticoduodenectomy	NCT05251233	Pancreatic Canc... Pancreas Cancer Ampullary Cance... Pancreas Neuroe... Pancreatitis Distal Extrahep... Duodenal Cancer	Placebo Pantoprazole	18 Years -	Washington University School of Medicine
Pantoprazole With Doxorubicin for Advanced Cancer Patients With Extension Cohort of Patients With Solid Tumours	NCT01163903	Advanced Solid ...	pantoprazole so... doxorubicin hyd...	18 Years -	University Health Network, Toronto

Spots Global Cancer Trial Database for pantoprazole

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