Advanced Solid TumoursPhase 1NCT01163903
Pantoprazole With Doxorubicin for Advanced Cancer Patients With Extension Cohort of Patients With Solid Tumours
A Phase 1 study testing pantoprazole sodium for injection and doxorubicin hydrochloride injection in people with Advanced Solid Tumours, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumours
- What is being tested?
- pantoprazole sodium for injection and doxorubicin hydrochloride injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2010to May 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Advanced Solid Tumours
- Being tested
- pantoprazole sodium for injection, doxorubicin hydrochloride injection
- Keywords
- Advanced solid tumours, Pantoprazole, Doxorubicin, PANTO IV, 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pantoprazole sodium for injectionDrug
Also called Pantoprazole, PANTO IV
Single 3-weekly doses of pantoprazole using the following dose escalation scheme for successive groups of patients: 80, 160, 240 and 320mg i.v. of pantoprazole to be given every 3 weeks, 30-60 (±5) minutes prior to doxorubicin. Treatment will be repeated on Day 1 of a 21-day cycle until radiographic or symptomatic progression or unacceptable toxicity or a maximum of 4 cycles (for patients who have received prior anthracyclines), and up to 8 cycles (for those with no prior exposure to anthracyclines).
doxorubicin hydrochloride injectionDrug
Also called ADRIAMYCIN PFS, ADRIAMYCIN, doxorubicin hydrochloride
60 mg/m2, IV, scheduled on day 1 of every 3-week interval, 30-60 (±5) minutes after pantoprazole administration.
| Study group | Role | What they receive |
|---|---|---|
| Pantoprazole and doxorubicin | Experimental | Not described Receives: Drug: pantoprazole sodium for injection; Drug: doxorubicin hydrochloride injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of recommended phase II dose (RP2D) of pantoprazole given with doxorubicin at 60mg/m2
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.
Measured: 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.
Secondary outcomes (4)
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.
Three or 6 patients will be treated per cohort for at least one cycle (21 days per cycle). If two patients experience DLTs, then accrual will stop at that level, and the next lower dose level in which six patients have been treated with no or only 1 DLT will be declared the RP2D. Once the RP2D has been identified, six additional patients will be treated at the RP2D to confirm its safety and tolerability. Patients will be assessed for toxicities using the overall safety profile as per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Measured: 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.
Assess the preliminary anti-tumour activity of the doxorubicin/pantoprazole by combination in patients with advanced solid tumours, by evaluating tumour response rate.
Response Evaluation Criteria in Solid Tumours (RECIST) will be used to determine radiological tumour response for measurable disease and disease progression. Changes in only the largest diameter (unidimensional measurement) of the tumour lesions are used in the RECIST criteria. Any radiological change should be confirmed using a second follow-up scan, 6 or more weeks later. For response there must be no new lesions and no evidence of progression of non-measurable lesions.
Measured: Radiologic evaluation (CT scan of chest, abdomen and pelvis) performed every 9 weeks
Evaluate the pharmacokinetics of doxorubicin and pantoprazole when given in combination by collecting venous blood samples at various timepoints throughout study drug administration.
Measured: Blood samples just before and at the end of pantoprazole and doxorubicin administration, and at 1, 2, 4, 8, 24, 48 and 72 hours after (first or second) drug administration for evaluation of serum levels of doxorubicin and pantoprazole
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.
Two cores of tumour tissue will be extracted within 24-48 hours of administration of doxorubicin and pantoprazole;1 core will be fixed for routine pathological examination and the 2nd will be fresh frozen. The latter will be sectioned in the experimental pathology laboratory and will be stained with antibodies which recognize tumour blood vessels and regions of hypoxia. Distribution of doxorubicin (which is fluorescent) in relation to the blood vessels in tumours, and in relation to hypoxic regions, will then be quantified using immunohistochemistry at an advanced optical microscopy facility.
Measured: Tumour biopsy within 24-48h after administration of doxorubicin (in consenting patients with disease amenable to biopsy)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2010 (estimated)
- Study startJul 2010
- Primary completionMar 2014
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumoursStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Princess Margaret Hospital, Canada
- Responsible party
- Sponsor
- Investigators
- Ian F Tannock, MD, PhD, DSc, Principal investigator, Princess Margaret Hospital, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01163903
- Sponsor's protocol ID
- DDP-IT-01
- Status last verified
- Jul 2015
- First submitted
- 13 Jul 2010
- Last updated
- 15 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01163903
- Acronym / sponsor ID
- DDP-IT-01
- Conditions
- Advanced Solid Tumours
- Keywords
- Advanced solid tumours, Pantoprazole, Doxorubicin, PANTO IV, Adriamycin, no standard treatment options, dose-escalation schedule, Phase I
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Princess Margaret Hospital, Canada
- Study start
- Jul 2010
- Primary completion
- Mar 2014 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 16 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pantoprazole and doxorubicin | Experimental | Drug: pantoprazole sodium for injection, Drug: doxorubicin hydrochloride injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
Key exclusion criteria (21 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pantoprazole sodium for injectionAlso: Pantoprazole, PANTO IVSingle 3-weekly doses of pantoprazole using the following dose escalation scheme for successive groups of patients: 80, 160, 240 and 320mg i.v. of pantoprazole to be given every 3 weeks, 30-60 (±5) minutes prior to doxorubicin. Treatment will be repeated on Day 1 of a 21-day cycle until radiographic or symptomatic progression or unacceptable toxicity or a maximum of 4 cycles (for patients who have received prior anthracyclines), and up to 8 cycles (for those with no prior exposure to anthracyclines). | Drug | Pantoprazole and doxorubicin |
| doxorubicin hydrochloride injectionAlso: ADRIAMYCIN PFS, ADRIAMYCIN, doxorubicin hydrochloride60 mg/m2, IV, scheduled on day 1 of every 3-week interval, 30-60 (±5) minutes after pantoprazole administration. | Drug | Pantoprazole and doxorubicin |
Primary outcome
Determination of recommended phase II dose (RP2D) of pantoprazole given with doxorubicin at 60mg/m2
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.
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.
4 secondary outcomes
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.
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.
Assess the preliminary anti-tumour activity of the doxorubicin/pantoprazole by combination in patients with advanced solid tumours, by evaluating tumour response rate.
Time frame: Radiologic evaluation (CT scan of chest, abdomen and pelvis) performed every 9 weeks
Evaluate the pharmacokinetics of doxorubicin and pantoprazole when given in combination by collecting venous blood samples at various timepoints throughout study drug administration.
Time frame: Blood samples just before and at the end of pantoprazole and doxorubicin administration, and at 1, 2, 4, 8, 24, 48 and 72 hours after (first or second) drug administration for evaluation of serum levels of doxorubicin and pantoprazole
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.
Time frame: Tumour biopsy within 24-48h after administration of doxorubicin (in consenting patients with disease amenable to biopsy)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ian F Tannock, MD, PhD, DSc principal investigator
Princess Margaret Hospital, Canada
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing pantoprazole sodium for injection and doxorubicin hydrochloride injection in people with Advanced Solid Tumours, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of recommended phase II dose (RP2D) of pantoprazole given with doxorubicin at 60mg/m2 (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2015.