Overview

Paricalcitol Addition to Chemotherapy in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma

Status:
Unknown status
Trial end date:
2021-06-30
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Barts & The London NHS Trust
Treatments:
Albumin-Bound Paclitaxel
Cisplatin
Ergocalciferols
Gemcitabine
Paclitaxel
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 21 days prior to day 1 of cycle 1 of treatment defined by the
following:

1. 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

2. Coagulation: INR and aPTT ≤1.5 x ULN.

3. 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)

8. Life expectancy ≥ 12 weeks.

9. Women of childbearing potential must agree not to become pregnant (e.g.
post-menopausal for at least 1 year, surgically sterile, or using effective
contraception) for the duration of the study and for 1 month after last dose of study
treatment. Women of child bearing potential must have a negative serum or urine
pregnancy test within 14 days of Cycle 1 Day 1 (preferably as close to the study
treatment day as possible). Both male and female patients of reproductive potential
must agree to use effective contraception from 2 weeks before the start of study
treatment and until 6 month (female participants) or 6 months (male participants)
after completion of treatment (as per protocol section 6.10.5).

10. Tumour sites amenable to repeated biopsies.

11. Willingness to undergo paired tumour biopsies during the trial

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. 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.

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. Current, serious, clinically significant cardiac arrhythmias as determined by the
investigator.

7. History of HIV infection.

8. Active, clinically significant serious infection requiring treatment with antibiotics,
antivirals or anti-fungals (see Section 6.10).

9. History of symptomatic genitourinary stones (e.g. kidney stones) within 12months of
Cycle 1 Day 1.

10. Pre-existing, clinically significant peripheral neuropathy ≥ G2

11. 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.

12. Patients with a history of pneumonitis

13. Patients with a history of a hearing impairment

14. Patients who have received any live vaccines within 4 weeks prior to trial
registration

15. 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.

16. 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.

17. Female patients who are pregnant or nursing.