A Randomised, double-blinded phase II study of gemcitabine and nab‐paclitaxel with CEND‐1/LSTA1 or placebo in patients with untreated metastatic pancreatic ductal adenocarcinoma
Purpose of the Study
Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have poor outcomes. Nevertheless, in the past few years, the development of more effective doublet and triplet chemotherapy regimens have improved median survival to approximately 8.5-11 months. The aim of the study is to investigate the activity and safety of CEND‐1/LSTA1 as an additive to first line gemcitabine and nab‐paclitaxel in people with untreated metastatic pancreatic ductal adenocarcinoma.
- Adults, 18 years or older with histologically confirmed metastatic pancreatic ductal adenocarcinoma or poorly differentiated carcinoma.
- Measurable disease according to RECIST 1.1.
- Archival tumour tissue for tertiary correlative studies (biopsy or resection of primary or metastasis). Fine needle aspirate (FNA) or brushings will not be accepted.
- ECOG performance of 0-1 (Appendix 2)
- Adequate renal and haematological function
- Adequate hepatic function, defined as: Bilirubin <1.5 X ULN (Upper Limit of Normal), AST or ALT ≤ 5x ULN.
If a person was recently stented with improving bilirubin, the person can be randomised with bilirubin up to 3 x ULN provided chemotherapy is not administered until within the stated thresholds.
- Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
- Study treatment both planned and able to start within 7 days after randomisation
- Signed, written informed consent.
- Uncontrolled metastatic disease to the central nervous system. To be eligible, known CNS metastases should have been treated with surgery and/or radiotherapy and the patient should have been receiving a stable dose of steroids for at least 2 weeks prior to randomisation, with no deterioration in neurological symptoms during this time.
- Prior chemotherapy or investigational anti‐cancer therapy for metastatic pancreatic adenocarcinoma. Prior treatments with curative intent or for locally advanced disease are allowed, provided the last dose of chemotherapy was administered more than 6 months prior to randomisation.
- Prior radiotherapy or major surgery (as defined by local investigator) within 14 days of starting treatment.
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anti-cancer therapy with the exception of alopecia, vitiligo and the laboratory values defined in the inclusion criteria. Participants with Grade ≥2 peripheral neuropathy are not allowed.
- Concurrent use of any other anti‐cancer therapy including chemotherapy, targeted therapy, immunotherapy or biological agents.
- Known allergy or hypersensitivity to any of the study drugs and excipients.
- Any significant active infection, including chronic active hepatitis B, hepatitis C, or HIV. Participants with known Hepatitis B/C infection will be allowed to participate providing evidence of viral suppression has been documented and the patient remains on appropriate anti-viral therapy.
- History of prior or synchronous malignancy within 2 years prior to randomisation.
- Concurrent illness, including severe infection that may jeopardise the ability of the person to undergo the procedures outlined in this protocol with reasonable safety.
- Neuroendocrine pancreatic carcinoma.
- Life expectancy of less than 3 months.
- Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to randomisation. Men must use a reliable means of contraception.
- Serious medical or psychiatric
DETAILED INFORMATION AVAILABLE
Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) please click here.
A/Prof Andrew Dean
Prof Timothy Price
A/Prof Marion Harris
Lisata Therapeutics Australia Pty LTD
Gut Cancer Foundation New Zealand