A Randomised, Double-blinded Phase II Study of Gemcitabine and Nab-Paclitaxel with CEND-1/LSTA1 (Certepetide) or Placebo in Patients with Untreated Metastatic Pancreatic Ductal Adenocarcinoma
A Randomised, double-blinded phase II study of gemcitabine and nab-paclitaxel with CEND-1/ LSTA1 (Certepetide) or placebo in patients on progression-free survival in patients with untreated metastatic pancreatic ductal adenocarcinoma
Australasian Gastro-Intestinal Cancer Trials Group
155 participants
May 11, 2022
Interventional
Conditions
Summary
The ASCEND clinical trial aims to measure the effect of adding LSTA1/CEND-1 (Certepetide), a new cancer drug or a placebo, to standard chemotherapy (gemcitabine and nab-paclitaxel) in patients who have untreated metastatic pancreatic cancer. Who is it for? You may be eligible for this study if you are aged 18 or older, you have been diagnosed with metastatic pancreatic ductal adenocarcinoma, and you have adequate liver and kidney function determined by blood tests. Study details Participants who choose to enrol in this study will be randomly allocated by chance (with 2/3 patients randomly assigned to the LSTA1/CEND-1 (treatment) to receive either LSTA1/CEND1 in addition to the standard chemotherapy (gemcitabine and nab-paclitaxel), or a placebo in addition to the standard chemotherapy. Both LSTA1/CEND1 and the placebo will be administered by an intravenous infusion over a 28-day treatment cycle. Participants will continue to receive these treatments every 28 days until the cancer is seen to have progressed, or until treatment side effects become intolerable. Participants will undergo continuous monitoring for side effects throughout treatment, as well as completing questionnaires, blood tests and CT scans every 8 weeks for up to 18 months after starting the treatment. It is hoped that this trial will provide information on whether LSTA1/CEND1 is safe and effective for the treatment of metastatic pancreatic cancer.
Eligibility
Inclusion Criteria22
- 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
- Adequate renal and haematological function
- Adequate hepatic function, defined as:
- Bilirubin <1.5 X ULN (Upper Limit of Normal), AST or ALT greater than or equal to 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.
- 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:
- a. Malignancy that was treated with curative intent and for which there has been no known active disease for greater than or equal to 2 years prior to randomisation.
- b. 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.
Exclusion Criteria3
- 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.
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Interventions
The study comprises of two cohorts, A and B. Patients was randomised 1:1 to cohort A or B, then subsequently randomised 2:1 in favour of the study intervention. Randomisation was stratified by age (<65 or =65), ECOG (0 or 1), presence of liver metastasis (yes or no), and sites. Cohort A patients will receive single dose of CEND-1/LSTA1 or single placebo regimen. Cohort B will receive 2 doses of CEND-1/LSTA1 or placebo. Participants will receive standard treatment of intravenous nab-paclitaxel (Dosage: 125mg/m2) and intravenous Gemcitabine (Dosage:1000mg/m2), on Day 1, 8 and 15 of each cycle. On each of these days, patients will also receive either intravenous CEND1/LSTA1 (3.2mg/kg IV) or an intravenous placebo. Each cycle will be 28 days. Treatment will continue until disease progression, unacceptable toxicity, investigator decision, occurrence of condition affecting patient safety, required use of non-permitted concomitant medication, patient decision, or failure to comply with protocol/study schedule. Site staff will monitor adherence to interventions from attendance information and discuss with investigator/coordinating centre to determine whether participation can continue.
Locations(24)
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ACTRN12621001290886