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

NCT01163903 | Completed Phase 1 DMC

• 1 other identifier: DDP-IT-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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. 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

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  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.

  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.

  Tumour biopsy within 24-48h after administration of doxorubicin (in consenting patients with disease amenable to biopsy)

Study Arms (1)

Pantoprazole and doxorubicin

EXPERIMENTAL

Drug: pantoprazole sodium for injection; Drug: doxorubicin hydrochloride injection

Interventions

pantoprazole sodium for injection DRUG

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).

Also known as: Pantoprazole, PANTO IV

Pantoprazole and doxorubicin

doxorubicin hydrochloride injection DRUG

60 mg/m2, IV, scheduled on day 1 of every 3-week interval, 30-60 (±5) minutes after pantoprazole administration.

Also known as: ADRIAMYCIN PFS, ADRIAMYCIN, doxorubicin hydrochloride

Pantoprazole and doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Patients who have previously received more than 240 mg/m2 doxorubicin or 300 mg/m2 epirubicin.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Princess Margaret Hospital, Canada: collaborator

Study Sites (1)

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Interventions

Pantoprazole; Injections; Doxorubicin

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Administration Routes; Drug Therapy; Therapeutics; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Ian F Tannock, MD, PhD, DSc

  Princess Margaret Hospital, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2010
• First Posted: July 16, 2010
• Study Start: July 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: May 1, 2015
• Last Updated: July 15, 2015

Record last verified: 2015-07

Locations

CA (1)