The ASCEND Study: Gemcitabine and Nab-Paclitaxel With CEND-1 or Placebo in Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma (ASCEND)

This is an interventional treatment trial for Pancreatic Ductal Adenocarcinoma Read More

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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, except:

  1. Malignancy that was treated with curative intent and for which there has been no known active disease for ≥2 years prior to randomisation.
  2. Curatively treated non-melanoma skin cancer, cervical cancer in situ, superficial transitional cell carcinoma of the bladder, stage 1 endometrial carcinoma, prostatic intraepithelial neoplasia, low-grade papillary thyroid cancer, untreated localised very low risk or low risk prostate cancer under observation.
• 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 conditions that might limit the ability of the person to comply with the protocol.