A Phase II Pilot Trial Of Paclitaxel Protein Bound and Gemcitabine Based Chemotherapy and the Addition Of Paricalcitol Upon Attainment of Stable or Progressive Disease in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Barts & The London NHS Trust
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Clinical benefit
Overview
Brief Summary
This is a phase II pilot trial of Paclitaxel Protein Bound and Gemcitabine based chemotherapy and the addition of Paricalcitol upon attainment of stable or progressive disease in eligible patients with untreated metastatic pancreatic ductal adenocarcinoma.
Detailed Description
Pancreatic cancer is the fourth-highest cancer killer worldwide with an overall 5 year survival of about 8%. The only potentially curative procedure, surgical excision, is feasible in a minority of patients, but even in these patients the majority (~80%) die within 5 years. This study aims to see if adding paricalcitol (a vitamin D analogue) to chemotherapy can slow down tumour growth in patients with previously untreated metastatic pancreatic cancer.
Studies have shown vitamin D can change the pancreatic tumour microenvironment from an immunologically suppressive (tumour growth promoting) to an immunologically hostile one, slowing down tumour growth in this way.
Patients with pancreatic cancer that has spread to other organs and who have adequate hepatic and renal function are eligible. Participants will receive chemotherapy (paclitaxel and gemcitabine, with or without cisplatin). On development of stable disease or disease progression, paricalcitol will be added to the chemotherapy regimen and participants will continue on this treatment until their cancer stops responding to treatment. After that participants will be followed up 3 monthly for the collection of disease status and survival data.
Participants will be asked to donate tumour and blood samples to allow the research team to look at the effects on the tumour biology.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Willing and able to provide written informed consent.
- •Ability to comply with the protocol.
- •Aged ≥ 18 years; male or female.
- •Histologically or cytologically confirmed metastatic (stage IV) pancreatic ductal adenocarcinoma.
- •Karnofsky performance status ≥
- •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
- •Adequate haematological and end-organ function, as per the local institutions reference ranges, within 21 days prior to day 1 of cycle 1 of treatment defined by the following:
- •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
- •Coagulation: INR and aPTT ≤1.5 x ULN.
- •Biochemistry: serum creatinine \< 1.5mg/dl, bilirubin \< 1.5 x ULN; AST / ALT ≤ 2.5 x ULN (or ≤ 5 x ULN in the presence of liver metastasis) calculated creatinine clearance ≥ 50ml/min (as measured by Cockcroft \& Gault)
Exclusion Criteria
- •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. In exceptional circumstances, if a patient has received paclitaxel protein bound and gemcitabine as first line chemotherapy for metastatic disease in exactly 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.
- •Palliative surgery and/or radiation treatment less than 4 weeks prior to initiation of study treatment.
- •Exposure to any investigational agent within 4 weeks prior to initiation of study treatment.
- •Evidence of central nervous system (CNS) metastasis (negative imaging study, if clinically indicated, within 28 days of Cycle 1 Day 1).
- •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.
- •Current, serious, clinically significant cardiac arrhythmias as determined by the investigator.
- •History of HIV infection.
- •Active, clinically significant serious infection requiring treatment with antibiotics, antivirals or anti-fungals (see Section 6.10).
- •History of symptomatic genitourinary stones (e.g. kidney stones) within 12months of Cycle 1 Day
- •Pre-existing, clinically significant peripheral neuropathy ≥ G2
Arms & Interventions
With Cisplatin
Paclitaxel Protein bound, Cisplatin, and Gemcitabine until stable or progressive disease, at which point Paricalcitol will be introduced.
Intervention: Paclitaxel protein bound (Drug)
With Cisplatin
Paclitaxel Protein bound, Cisplatin, and Gemcitabine until stable or progressive disease, at which point Paricalcitol will be introduced.
Intervention: Cisplatin (Drug)
With Cisplatin
Paclitaxel Protein bound, Cisplatin, and Gemcitabine until stable or progressive disease, at which point Paricalcitol will be introduced.
Intervention: Gemcitabine (Drug)
With Cisplatin
Paclitaxel Protein bound, Cisplatin, and Gemcitabine until stable or progressive disease, at which point Paricalcitol will be introduced.
Intervention: Paricalcitol (Drug)
Without Cisplatin
Paclitaxel Protein bound and Gemcitabine until stable or progressive disease, at which point Paricalcitol will be introduced.
Intervention: Paclitaxel protein bound (Drug)
Without Cisplatin
Paclitaxel Protein bound and Gemcitabine until stable or progressive disease, at which point Paricalcitol will be introduced.
Intervention: Gemcitabine (Drug)
Without Cisplatin
Paclitaxel Protein bound and Gemcitabine until stable or progressive disease, at which point Paricalcitol will be introduced.
Intervention: Paricalcitol (Drug)
Outcomes
Primary Outcomes
Clinical benefit
Time Frame: Time frame will be measured from date of Paricalcitol until the date of documented progression or date of death from any cause, whichever came first, expected maximum length of 7 months.
To determine the clinical benefit of adding paricalcitol to the regimens of either paclitaxel protein bound plus gemcitabine or paclitaxel protein bound plus cisplatin plus gemcitabine for patients with stable or progressive metastatic PDA.
Secondary Outcomes
No secondary outcomes reported