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

Inclusion criteria

• Patients must have histologically or cytologically proven advanced solid tumours for whom no standard anticancer therapy exists
• Measureable and non-measureable disease are both eligible, but disease must be evaluable as defined by RECIST 1.1.
• Patients >18 years old
• At least 21 days since last chemotherapy regimen and/or radiotherapy
• Recovery from all reversible adverse events of previous anticancer therapies to baseline or to grade < or =1, except for alopecia.
• Patients must have documented evidence of disease progression on prior systemic therapy.
• ECOG Performance Status of 0 or 1
• 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
• Patient consent must be obtained according to Institutional REB requirements. The patient must sign the consent form prior to registration.
• Patients must be accessible for treatment and follow-up.
• Previous Therapy

• 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.
• 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.
• Previous Surgery: Previous surgery is permitted provided that wound healing has occurred.
• Hormonal Therapy: Patients may have had prior hormonal therapy. All hormonal agents must be discontinued at least 3 weeks prior to study entry.
• Laboratory Requirements (must be done within 7 days prior to registration)

• Neutrophil count (ANC) > or = 1.5 x 10^9/L
• Hemoglobin > or = 90 g/L
• Platelet count > or = 100 x 10^9/L
• Bilirubin <1.5 x UNL
• AST or ALT < or = 2 x UNL
• Creatinine < or = 1.5 x UNL or creatinine clearance > or = 50mL/min

Exclusion criteria

• Patients who have previously received more than 240 mg/m2 doxorubicin or 300 mg/m2 epirubicin.
• Patients receiving concurrent treatment with experimental drugs or anti-cancer therapy.
• Patients who are receiving drugs that are known to interact with pantoprazole, including:

• The anti-fungal agents fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole;
• The antiviral agents: atazanavir, delavirdine, indinavir, nelfinavir, raltegravir, saquinavir, tipranavir;
• The anticoagulant agents: clopidogrel, dabigatran;
• The immunosuppressive agent: mycophenolate
• The anti-inflammatory agent: mesalamine
• Patients who are receiving oral pantoprazole or other PPI inhibitors may participate if these agents are discontinued at least 7 days before trial entry.
• 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.
• Patients who have a history of clinically significant cardiac disease, including:

• Unstable angina/ acute coronary syndrome
• Congestive heart failure
• Myocardial infarction within the past year
• Clinically significant arrhythmia
• Pericarditis or myocarditis
• Symptomatic valvular disease Patients with well-controlled hypertension, uncomplicated mitral valve prolapsed or other stable cardiac conditions are eligible.
• 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.
• 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.
• Patients unable or unwilling to give written, informed consent prior to study participation.
• Women who are pregnant or nursing.