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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

Phase 1
18 Years
Open (Enrolling)
Advanced Solid Tumours

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Trial Information

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

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

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

3. Previous Surgery: Previous surgery is permitted provided that wound healing has

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

2. Patients receiving concurrent treatment with experimental drugs or anti-cancer

3. Patients who are receiving drugs that are known to interact with pantoprazole,

1. The anti-fungal agents fluconazole, itraconazole, ketoconazole, posaconazole,

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

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

10. Women who are pregnant or nursing.

Type of Study:


Study Design:

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

Outcome Measure:

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

Outcome Description:

To determine the recommended phase II dose (RP2D) of pantoprazole given with doxorubicin at 60mg/m2 when administered to adult patients with advanced solid tumours.

Outcome Time Frame:

Treatment until documented progression or up to 8 21-day cycles (4 cycles if prior anthracyclines received). All patients followed for late toxicities, every 3 months for 1 year or until all drug related toxicities are resolved/become unrelated.

Safety Issue:


Principal Investigator

Ian F Tannock, MD, PhD, DSc

Investigator Role:

Principal Investigator

Investigator Affiliation:

Princess Margaret Hospital, Canada


Canada: Ethics Review Committee

Study ID:




Start Date:

July 2010

Completion Date:

September 2014

Related Keywords:

  • Advanced Solid Tumours
  • Advanced solid tumours
  • Pantoprazole
  • Doxorubicin
  • Adriamycin
  • no standard treatment options
  • dose-escalation schedule
  • Phase I
  • single-centre
  • open label
  • dose finding
  • recommended phase II dose
  • proton pump inhibitor
  • advanced cancer
  • anthracycline
  • gastric acid secretion
  • Neoplasms