DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Pantoprazole With Doxorubicin for Advanced Cancer Patients With Extension Cohort of Patients With Solid Tumours

Information source: University Health Network, Toronto
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Advanced Solid Tumours

Intervention: pantoprazole sodium for injection (Drug); doxorubicin hydrochloride injection (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: University Health Network, Toronto

Official(s) and/or principal investigator(s):
Ian F Tannock, MD, PhD, DSc, Principal Investigator, Affiliation: Princess Margaret Hospital, Canada


This is a single-centre, open label, dose finding, phase I study to determine the recommended phase II dose (RP2D) for the combination of doxorubicin and pantoprazole in patients with advanced tumours and no standard treatment options. A minimum of 3 patients will be enrolled per dose level and intra-patient dose escalation is not permitted. Once the RP2D has been identified, six additional patients with metastatic solid tumours will be treated at the RP2D to confirm its tolerability.

Clinical Details

Official title: A Phase I Study Evaluating the Proton Pump Inhibitor Pantoprazole in Combination With Doxorubicin for Advanced Cancer Patients With an Extension Cohort of Patients With Solid Tumours

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Determination of recommended phase II dose (RP2D) of pantoprazole given with doxorubicin at 60mg/m2

Secondary outcome:

Characterize the safety and tolerability of the combination by determining dose-limiting toxicities (DLTs). Toxicities evaluated and graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Assess the preliminary anti-tumour activity of the doxorubicin/pantoprazole by combination in patients with advanced solid tumours, by evaluating tumour response rate.

Evaluate the pharmacokinetics of doxorubicin and pantoprazole when given in combination by collecting venous blood samples at various timepoints throughout study drug administration.

Evaluate (in selected patients with lesions amenable to biopsy) the influence of pantoprazole on distribution of doxorubicin in tumour tissue. Tumour tissue extracted after administration of doxorubicin/pantoprazole.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


Inclusion Criteria: 1. Patients must have histologically or cytologically proven advanced solid tumours for whom no standard anticancer therapy exists 2. Measureable and non-measureable disease are both eligible, but disease must be evaluable as defined by RECIST 1. 1. 3. Patients >18 years old 4. At least 21 days since last chemotherapy regimen and/or radiotherapy 5. Recovery from all reversible adverse events of previous anticancer therapies to baseline or to grade < or =1, except for alopecia. 6. Patients must have documented evidence of disease progression on prior systemic therapy. 7. ECOG Performance Status of 0 or 1 8. Adequate cardiovascular function and no history of serious cardiac diseases (see Exclusion criteria for definition) Left ventricular ejection fraction > 50% by multi-gated nuclear angiogram 9. Patient consent must be obtained according to Institutional REB requirements. The patient must sign the consent form prior to registration. 10. Patients must be accessible for treatment and follow-up. 11. Previous Therapy 1. Chemotherapy: Patients can have had limited exposure to prior anthracyclines defined as no more than a total dose of 240 mg/m2 of doxorubicin or 300 mg/m2 of epirubicin (e. g. as received in the AC x 4 or FEC x 3 adjuvant regimens). Patients with prior exposure to other cardiotoxic anticancer drugs (e. g. mitoxantrone) are not eligible. 2. Radiation: Patients may have had prior radiation therapy (including that to the breast or chest wall) provided that has not exceeded 25% of the bone marrow reserve. 3. Previous Surgery: Previous surgery is permitted provided that wound healing has occurred. 4. Hormonal Therapy: Patients may have had prior hormonal therapy. All hormonal agents must be discontinued at least 3 weeks prior to study entry. 12. Laboratory Requirements (must be done within 7 days prior to registration) 1. Neutrophil count (ANC) > or = 1. 5 x 10^9/L 2. Hemoglobin > or = 90 g/L 3. Platelet count > or = 100 x 10^9/L 4. Bilirubin <1. 5 x UNL 5. AST or ALT < or = 2 x UNL 6. Creatinine < or = 1. 5 x UNL or creatinine clearance > or = 50mL/min Exclusion Criteria: 1. Patients who have previously received more than 240 mg/m2 doxorubicin or 300 mg/m2 epirubicin. 2. Patients receiving concurrent treatment with experimental drugs or anti-cancer therapy. 3. Patients who are receiving drugs that are known to interact with pantoprazole, including: 1. The anti-fungal agents fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole; 2. The antiviral agents: atazanavir, delavirdine, indinavir, nelfinavir, raltegravir, saquinavir, tipranavir; 3. The anticoagulant agents: clopidogrel, dabigatran; 4. The immunosuppressive agent: mycophenolate 5. The anti-inflammatory agent: mesalamine 4. Patients who are receiving oral pantoprazole or other PPI inhibitors may participate if these agents are discontinued at least 7 days before trial entry. 5. Patients with untreated brain or meningeal metastases. (MR or CT scans are not required to rule this out unless there is a clinical suspicion of CNS disease). Patients with treated and stable brain metastases are eligible providing that they have radiological evidence of disease stabilization of at least 3 months duration and are asymptomatic. 6. Patients who have a history of clinically significant cardiac disease, including: 1. Unstable angina/ acute coronary syndrome 2. Congestive heart failure 3. Myocardial infarction within the past year 4. Clinically significant arrhythmia 5. Pericarditis or myocarditis 6. Symptomatic valvular disease Patients with well-controlled hypertension, uncomplicated mitral valve prolapsed or other stable cardiac conditions are eligible. 7. Patients with active or uncontrolled infections or with serious illnesses or medical conditions that would not permit the patient to be managed according to the protocol. 8. Patients with a known bleeding disorder. Patients who are on stable anticoagulation with warfarin or s. c. heparin products are eligible. Patients receiving clopidogrel are excluded. 9. Patients unable or unwilling to give written, informed consent prior to study participation. 10. Women who are pregnant or nursing.

Locations and Contacts

Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada
Additional Information

Starting date: July 2010
Last updated: July 14, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017