| Eligibility |
Inclusion Criteria:
1. Written informed consent obtained prior to any study-related procedures.
2. Incurable recurrent, locally advanced or metastatic pancreatic adenocarcinoma.
3. Histologically or cytologically confirmed pancreatic adenocarcinoma.
4. No prior chemotherapy for incurable, locally advanced unresectable or metastatic
pancreatic cancer. Patients may have received prior chemotherapy in the neo-adjuvant
or adjuvant setting provided they have a minimum treatment-free interval of 3 months.
5. At least one measurable lesion according to RECIST criteria (Version 1.1). Patients
with bone only disease are not eligible.
6. Aged 18 years or older
7. ECOG performance status 0 - 2
8. Adequate haematological, renal and hepatic function measured within 28 days prior to
commencing study:
- Total bilirubin = ULN (or = 3 x ULN (= grade 2) for patients with liver
involvement)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x ULN (=
grade
1) (= 5 x ULN for patients with liver involvement by pancreatic cancer).
- Glomerular filtration rate (GFR) = 30mL/min/1.73 m2 (= grade 2) for patients with
serum creatinine levels above or below the institutional normal range. If using
creatinine clearance, actual body weight should be used for calculating
creatinine clearance (e.g., using the Cockroft-Gault formula). For patients with
a Body Mass Index (BMI) >30 kg/m2, lean body weight should be used instead.
- Platelet count = 100 x 109/L.
- Haemoglobin (Hb) = 8 g/dL (= grade 2)
- Absolute neutrophil count (ANC) = 1.5 x 109/L (= grade 1)
- Corrected serum calcium of = 2.9 mmol/L (= grade 1).
9. Life expectancy of at least 12 weeks.
10. Women of childbearing potential and sexually active males must agree to use highly
effective contraceptive measures. This applies from starting treatment until at least
6 months after the last study drug administration. The investigator or a designated
associate is required to advise the patient how to achieve an adequate birth control.
Highly effective contraception is defined in the study as methods that achieve a
failure rate of less than 1% per year when used consistently and correctly. Such
methods include:
i. Combined (oestrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation (oral, intravaginal, transdermal). ii. Progestogen-only
hormonal contraception associated with inhibition of ovulation (oral, injectable and
implantable). iii. Intrauterine device (IUD). iv. Intrauterine hormone-releasing
system (IUS). v. Bilateral tubal occlusion. vi. Successfully vasectomised partner.
vii. Sexual abstinence.
Exclusion Criteria:
1. Treated with other investigational drugs within 28 days or 5.5 half-lives of treatment
start; in addition, concurrent alternative (complementary) medications are excluded
within 28 days of treatment start.
2. Known brain metastases, unless previously treated and well-controlled for at least 2
months.
3. Dementia, altered mental status, or any other psychiatric condition that would
interfere with the patient's safety or informed consent
4. History of other malignancy other than pancreatic cancer. However, patients who have
been disease free from another malignancy for at least 5 years, or patients with a
history of resected non-melanoma skin cancer or successfully treated in situ cancer
and superficial bladder tumours (Ta, Tis, T1) are eligible.
5. Known history of hypercalcaemia.
6. Presence or history of symptomatic kidney stones in the last 5 years.
7. Active, clinically serious infections > grade 2 (CTCAE v5.0).
8. Greater than or equal to grade 2 sensory or motor neuropathy
9. Uncontrolled intercurrent illness, including, but not limited to uncontrolled
bacterial, viral, or fungal infection(s) requiring systemic therapy, symptomatic
congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia,
or social situation that would affect compliance with the requirements of this study.
10. GI tract disease resulting in an inability to take oral medications, malabsorption
syndrome, where previous surgical procedures affect absorption and uncontrolled
inflammatory bowel disease.
11. History of diseases known to be associated with calcium disorders, including: ongoing
hyperparathyroidism and Sarcoidosis.
12. Hypersensitivity to any of the excipients of gemcitabine, Nab-paclitaxel or
Paricalcitol.
13. Known vitamin D toxicity
14. Undergoing treatment with the following therapies and medications:
1. Concurrent use of drugs known to influence serum calcium such as thiazide
diuretics, teriparatide (recombinant parathyroid hormone), calcitonin and
multivitamin supplements containing > 400 IU of vitamin D or calcium.
2. Current use of drugs which could influence bioavailability of paricalcitol (such
as magnesium-containing antacids, bile-resin binders).
3. Current use of strong inhibitors of CYP3A4 or CYP2C8.
4. Current use of inducers of CYP3A4 or CYP2C8.
5. Phosphate related medicinal products.
Note:
- Zoledronate or denosumab for patients with bone metastasis is allowed. Note patients
with bone only disease are not eligible.
- Calcium intake is not restricted, but calcium supplementation is not permitted.
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