Stage IV pancreatic adenocarcinoma MedDRA version: 21.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Abraxane
Product Name: Abraxane
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: Nab-paclitaxel
CAS Number: L01CD01
Other descriptive name: paclitaxel formulated as albumin bo
Sponsors
Barts Health NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide written informed consent. 2. Ability to comply with the protocol. 3. Aged = 18 years; male or female. 4. Histologically or cytologically confirmed metastatic (stage IV) pancreatic ductal adenocarcinoma. 5. Karnofsky performance status =70. 6. At least one lesion that can be measured accurately at baseline as =10mm in the longest diameter (except lymph nodes which must have a short axis =15mm) with CT/MRI and which is suitable for repeated measurements per RECIST v1.1 7. Adequate haematological and end-organ function, as per the local institutions reference ranges, within 72 hrs prior to day 1 of cycle 1 of treatment defined by the following: a. Haematology: ANC >1.5 x 109/L (>1500 cells / mm3); Platelet count > 100 x 109/L (>100,000 cells/mm3); haematocrit level >27% for females or >30% for males b. Coagulation: INR and aPTT =1.5 x ULN. c. Biochemistry: serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatments in the adjuvant setting with gemcitabine and/or 5-FU or gemcitabine administered as a radiation sensitizer are allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. If a patient has received paclitaxel protein bound and gemcitabine as first line chemotherapy for metastatic disease in the same way as mandated in the current trial, they can be considered eligible to be enrolled directly to the add on paricalcitol component of the trial. Unless the patient meets inclusion criteria 12. 2. Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment. 3. Exposure to any investigational agent within 4 weeks prior to initiation of study treatment. 4. Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 28 days of Cycle 1 Day 1). 5. History of other malignancies (except cured basal or squamous cell carcinoma, superficial bladder cancer, prostate cancer in active surveillance, or carcinoma in situ of the cervix) unless documented free of cancer for =2 years. 6. Pre-existing hypercalcaemia, defined as baseline serum calcium (corrected for albumin) above the institutional ULN. 7. Current, serious, clinically significant cardiac arrhythmias as determined by the investigator. 8. History of HIV infection. 9. Active, clinically significant serious infection requiring treatment with antibiotics, antivirals or anti-fungals (see Section 6.10). 10. History of symptomatic genitourinary stones (e.g. kidney stones) within 12months of Cycle 1 Day 1. 11. Pre-existing, clinically significant peripheral neuropathy = G2 12. Hypersensitivity to the active study drug substance or to any of its excipients as listed in section 6 of the SmPC of each study drug. 13. Patient is on prohibited concurrent medication (see Section 6.10). In particular, vitamin D and calcium supplements must be stopped at the time of enrolment and for the duration of study treatment. 14. Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that, in the investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of study treatment, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent. 15. Female patients who are pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: On disease progression after the addition of paricalcitol.;Main Objective: To determine the clinical benefit of adding paricalcitol to the regimen of paclitaxel protein bound plus cisplatin plus gemcitabine for patients with progressive metastatic PDA. ;Secondary Objective: • Evaluate the mechanisms of disease progression of patients with metastatic PDAC to paclitaxel protein bound plus cisplatin plus gemcitabine • To assess the pharmacodynamics effect of paricalcitol for patients with metastatic PDA • Evaluate the safety of cisplatin plus paclitaxel protein bound plus gemcitabine plus paricalcitol. Tertiary/Exploratory The results of any exploratory analysis will not be included in the clinical study report and may be reported separately from the main study results: • To evaluate the pharmacodynamic effects of paricalcitol on PDA on core biopsies collected at baseline prior to the addition of paricalcitol and after 2 cycles of the triplet regimen plus paricalcitol (6 weeks): Stromal content (collagen and hyaluronan), CD31 staining, PD-1/ PDl-1 staining and expression, IHC evaluation of key immune cell populations (cytotoxic T Cells, TAMs, MDSCs, and Tregs), Clonality of intra-tumoural T cells by TSR sequencing (a measure of intratumoural response);Primary end point(s): To evaluate the response after the administration of Paricalcitol to those with PDA who have progressed on paclitaxel protein bound plus cisplatin plus gemcitabine by using RECIST 1.1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To evaluate the treatment-related toxicities in this patient population. - To evaluate the change in CA 19-9 (or CA 125, or CEA if not expressers of CA 19-9) in this patient population. - To evaluate the change in parathyroid hormone (PTH) in individuals treated with paricalcitol - To monitor and measure the serum levels of Vitamin D 25-OH with every 3 cycles of therapy ;Timepoint(s) of evaluation of this end point: - From consent to safety visit - Every 3 weeks while on study treatment - Every 3 weeks while on study treatment - Every 3 weeks while on study treatment | — |
Countries
United Kingdom
Contacts
Public ContactDr Sarah Slater
Barts Health NHS Trust
Outcome results
None listed