Paricalcitol Trial: Phase II, Open Label Clinical Trial of Paricalcitol in Combination With Gemcitabine/ Nab-Paclitaxel Therapy in Advanced Pancreatic Cancer

NCT ID: NCT04617067

Last Updated: 2024-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-16
• Study Completion Date: 2022-09-30

Brief Summary

The trial is designed to establish whether adding a vitamin D analogue, Paricalcitol, to standard chemotherapy treatment, Gemcitabine and Nab-paclitaxel, can improve the outcomes for patients with advanced pancreatic cancer.

Detailed Description

This is an open-label phase II multi-centre single arm study which proposes to test the anti-tumour efficacy of paricalcitol, in combination with GEM/Nab-paclitaxel in patients with advanced metastatic pancreatic cancer.

Conditions

Advanced Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All Patients

Open Label: Paricalcitol 12mcg once daily, orally every day of each 28 day cycle PLUS GEM (1000mg/m2) and Nab-paclitaxel (Abraxane®) (125mg/m2) on days 1, 8 and 15 of each cycle.

Group Type: EXPERIMENTAL

Paricalcitol

Intervention Type: DRUG

Paricalcitol 12mcg, administered orally on every day of each 28-day cycle.

Gemcitabine (GEM) and Nab-paclitaxel

Intervention Type: DRUG

GEM (at 1,000 mg/m2) and Nab-paclitaxel (at 125 mg/m2 of bodysurface area), administered weekly for 3 of every 4 weeks (on days 1, 8 and 15 only).

Interventions

Paricalcitol

Paricalcitol 12mcg, administered orally on every day of each 28-day cycle.

Intervention Type: DRUG

Gemcitabine (GEM) and Nab-paclitaxel

GEM (at 1,000 mg/m2) and Nab-paclitaxel (at 125 mg/m2 of bodysurface area), administered weekly for 3 of every 4 weeks (on days 1, 8 and 15 only).

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Trials Ireland

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Prof. Bryan Hennessy

Role: PRINCIPAL_INVESTIGATOR

Beaumont Hospital

Locations

Tallaght University Hospital

Dublin, Dublin 24, Ireland

St. Vincent's University Hospital

Dublin, Dublin 4, Ireland

Beaumont Hospital

Dublin, Dublin 9, Ireland

Cork University Hospital

Cork, , Ireland

University Hospital Limerick

Limerick, , Ireland

University Hospital Waterford

Waterford, , Ireland

Countries

Ireland

Other Identifiers

2020-000073-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTRIAL-IE 19-33

Identifier Type: OTHER

Identifier Source: secondary_id

CTRIAL-IE 19-33

Identifier Type: -

Identifier Source: org_study_id