Metastatic Pancreatic Cancer
Conditions
Keywords
Low Dose OXIRI (LDOXIRI), Pancreatic Cancer, Irinotecan, Oxaliplatin, Capecitabine, Pharmacokinetics, Metronomic Chemotherapy, UGT1A1
Brief summary
This is a single-centre, non-randomized, open label phase II trial to be conducted at the National Cancer Centre, Singapore (NCCS). Patients diagnosed with metastatic PDAC will be eligible to enrol. The investigators hypothesize the anticancer activity of low dose OXIRI (LD-OXIRI) regimen comprising of metronomic oxaliplatin (O) and metronomic capecitabine (xeloda; X) in combination with UGT1A1-directed dosing of irinotecan (IRI) to be a tolerable regimen in patients with advanced PDAC and will lead to a favourable response rate. Patients will be prospectively enrolled in two stages - In stage 1, patients will be recruited and evaluated for response and toxicity. In stage 2, more patients will be recruited for further evaluation of response and toxicity.
Detailed description
Eligible patients will be recruited from the National Cancer Centre, Singapore (NCCS). Patients will be referred for assessment by the primary physician to a study investigator for screening. Informed written consent for entry into the trial will be obtained from the patient by a delegated investigator. All patients eligible for study entry will receive the LD-OXIRI regimen at the National Cancer Centre, Singapore. All concomitant medication taken during the study must be recorded. If a drug is administered prophylactically, this must be noted. The patients will not receive any other investigational drugs while on this study. There will be a screening period of 28 days, a treatment period till disease progression or unacceptable toxicity, and a post-treatment follow up period of up to 24 months.
Interventions
DRUGLow Dose OXIRI (LD-OXIRI)
The LD-OXIRI regimen will be administered in the following sequence: * metronomic capecitabine (Xeloda; X) 650mg/m2 will administered twice a day on a daily a continuous basis; * intravenous metronomic oxaliplatin (O) 50 mg/m2 will be infused over 120 minutes on days 1 and 8 of a 21 day-cycle; followed by * intravenous irinotecan (I) will be infused over 90 minutes on days 1 and 8 of a 21 day-cycle. The dose of irinotecan will be based on the particular patient's UGT1A1\*6 and UGT1A1\*28 genotype status.
Sponsors
National Cancer Centre, Singapore
National Medical Research Council (NMRC), Singapore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
43 patients will be enrolled in two stages - In stage 1, a total of 19 patients will be recruited and evaluated for response and toxicity. In stage 2, another 24 patients will be recruited for further evaluation of response and toxicity. Up to 7 patients will be recruited to account for any drop outs (i.e. up to total of 50 patients).
Eligibility
Sex/Gender
ALL
Age
21 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
The patient must meet all of the inclusion criteria to participate in the study. 1. Aged above 21 2. Histopathological diagnosis of pancreatic cancer 3. Advanced disease not amenable to curative resection (locally advanced or metastatic disease) 4. Measureable disease by RECIST 1.1 criteria 5. Life expectancy of at least 12 weeks 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 7. Adequate hematologic function (granulocyte count ≥ 1.5 × 10\*\*9/L, platelet count ≥ 100 × 10\*\*9/L), 8. Adequate hepatic function (total bilirubin ≤ 1.5 x the upper limits of normal \[ULN\], AST and ALT, ALP ≤ 3 x ULN or \< 5 x ULN in case of hepatic involvement), 9. Adequate renal function (creatinine clearance \> 50 mL/min) will be eligible for inclusion into the study. 10. Able to provide written and informed consent
Exclusion criteria
Any patient meeting any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR). | Up to 3 years. | The proportion of patients who have a partial or complete response as specified in RECIST 1.1. |
| Clinical Benefit Rate (CBR). | Up to 3 years. | The percentage of advanced cancer patients who achieve complete response, partial response, or at least six months of stable disease as specified in RECIST 1.1. |
| The Grade 3-5 Toxicity Rate. | Up to 3 years. | The proportion of patients who have adverse event(s) with Grade 3-5 toxicity as defined in CTCAE 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration [(Cmax)] of low dose Capecitabine and its intermediary metabolites (5'-deoxy-5-fluorocytidine [DFCR] and 5'- deoxy-5-fluorouridine [DFUR]) and 5FU. | At predose, 1 hr, end of irinotecan infusion on Cycle 1 Day 1 (each cycle is 21 days) | Maximum plasma concentration \[(Cmax)\] of low dose capecitabine and its intermediary metabolites (5'-deoxy-5-fluorocytidine \[DFCR\] and 5'- deoxy-5-fluorouridine \[DFUR\]) and 5FU at Cycle 1 Day 1. |
| Trough concentration of low dose capecitabine and its intermediary metabolites and 5FU. | At predose of Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 21 days) | Trough concentration of low dose capecitabine and its intermediary metabolites (5'-deoxy-5-fluorocytidine \[DFCR\] and 5'- deoxy-5-fluorouridine \[DFUR\]) and 5FU. |
| Immunophenotyping from extracted peripheral blood mononuclear cells (PBMCs) - measurement of cytokine and chemokine concentrations in picograms per milliliters using multiplex flow cytometry. | Up to 3 years. | Immunophenotyping from extracted peripheral blood mononuclear cells (PBMCs) - measurement of cytokine and chemokine concentrations in picograms per milliliters using multiplex flow cytometry at these time-points: at predose, end of oxaliplatin infusion, end of irinotecan infusion on Cycle 1 Day 1 (each cycle is 21 days); at predose of Cycle 2 Day 1 and at disease progression (up to three years). |
| Genomic analysis of circulating tumour DNA (ctDNA). | Up to 3 years. | Genomic analysis of circulating tumour DNA (ctDNA) from whole blood at these time-points: at predose of every two cycles (Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, etc - each cycle is 21 days) and at disease progression (up to three years). |
| Identification of exosomal proteins secreted by extracellular vesicles from plasma. | Up to 3 years. | Identification of exosomal proteins secreted by extracellular vesicles from plasma using mass spectrometry, at the following time-points: at predose, end of oxaliplatin infusion, end of irinotecan infusion on Cycle 1 Day 1 (each cycle is 21 days); at predose of Cycle 2 Day 1 and at disease progression (up to three years). |
| Progression-free survival (PFS). | Up to 3 years. | Time from first dose of treatment to disease progression or death, whichever comes first. |
| Overall survival (OS). | Up to 3 years. | Time from first dose to death. |
Countries
Singapore
Contacts
CONTACTDr Joycelyn LEE, MBBS, MRCP (UK), M Med
CONTACTTze Wei LIM
PRINCIPAL_INVESTIGATORDr Joycelyn LEE, MBBS, MRCP (UK), M Med
National Cancer Centre, Singapore
Outcome results
None listed