None listed
Conditions
Brief summary
This study aims to assess the safety and tolerability of a new cancer treatment drug, LSTA1, in combination with durvalumab, gemcitabine and nab-paclitaxel, as first-line treatment for patients with locally advanced pancreatic ductal adenocarcinoma (PDAC). Who is it for? You may be eligible for this study if you are aged 18 years or older (or aged 20 or older if Japanese), you have been diagnosed with locally advanced pancreatic ductal adenocarcinoma and you have not yet started treatment for your cancer. You will also need to meet certain health criteria prior to being eligible for this study. Study details Participants who choose to enrol in this study will be randomly allocated by chance (similar to flipping a coin) to one of 3 treatment groups. Participants allocated to the first treatment group will receive gemcitabine, nab-paclitaxel and two placebo treatments. Participants allocated to the second treatment group will receive gemcitabine, nab-paclitaxel, LSTA1 and one placebo treatment. Participants allocated to the third treatment group will receive gemcitabine, nab-paclitaxel, LSTA1 and durvalumab treatments. All treatments will be administered on set days of a 28-day treatment cycle. Participants will continue to receive their allocated treatments every 28 days unless they experience any serious side effects, they have disease progression or such a time that their health deteriorates to the point where the treatment is no longer practicable . During treatment, participants will be asked to undergo blood tests, imaging and a biopsy to determine how the treatment is affecting their cancer. It is hoped this research will determine whether adding the new cancer treatment drug, LSTA1 and immunotherapy to currently used cancer treatment drugs is safe and whether it has any effect on cancer cells. If this study finds that LSTA1 is safe to use in combination with the current cancer treatment drugs, it may be expanded to a larger study to further assess the effect of LSTA1 on cancer cells for patients with locally advanced pancreatic ductal adenocarcinoma. Thus far, we have not been able to get immunotherapy to engage with pancreatic cancer cells. Early studies, however, indicate that LSTA1 changes the tumour environment to make the immune cells work more effectively. This mechanism decreases immunosuppressive Tregs (Regulatory T cells (Tregs) which are a specialised subpopulation of T cells that act to suppress immune response against the tumour) and increases the percentage of cancer-fighting CD8+ T cells within the tumour. (CD8+T cells can mount a response against pathogens by secreting cytokines and can defend against tumours by directly killing transformed cells.)
Interventions
Cohort 2:
Gemcitabine (1,000mg/m2 over 30 minutes +/- 3 minutes; intravenously; Day 1 (D1), Day 8 (D8), Day 15 (D15) of every 28 day cycle) + Nab-Paclitaxel (125mg/m2 over 30 minutes +/- 3 minutes; intravenously; D1, D8, D15 of every 28 day cycle) + LSTA1 (3.2mg/kg over 1 minute +/-30 seconds; intravenously; D1, Day 2 (D2), D8, D15, Day 16 (D16) of every 28 day cycle) + Placebo Durvalumab (750mg over 60 minutes +/- 6 minutes; intravenously; D1, D15 of every 28 day cycle). All 4 drugs will be a
Cohort 2: Gemcitabine (1,000mg/m2 over 30 minutes +/- 3 minutes; intravenously; Day 1 (D1), Day 8 (D8), Day 15 (D15) of every 28 day cycle) + Nab-Paclitaxel (125mg/m2 over 30 minutes +/- 3 minutes; intravenously; D1, D8, D15 of every 28 day cycle) + LSTA1 (3.2mg/kg over 1 minute +/-30 seconds; intravenously; D1, Day 2 (D2), D8, D15, Day 16 (D16) of every 28 day cycle) + Placebo Durvalumab (750mg over 60 minutes +/- 6 minutes; intravenously; D1, D15 of every 28 day cycle). All 4 drugs will be administered for a total of 6 cycles or until disease progression or unacceptable adverse event. Cohort 3: Gemcitabine (1,000mg/m2 over 30 minutes +/- 3 minutes; intravenously; D1, D8, D15 of every 28 day cycle) + Nab-paclitaxel (125mg/m2 over 30 minutes +/- 3 minutes; intravenously; D1, D8, D15 of every 28 day cycle) + LSTA1 (3.2mg/kg over 1 minute +/-30 seconds; intravenously; D1, D2, D8, D15, D16 of every 28 day cycle) + Durvalumab (750mg over 60 minutes +/- 6 minutes; intravenously; D1, D15 of every 28 day cycle). All 4 drugs will be administered for a total of 6 cycles or until disease progression or unacceptable adverse event. Placebo Durvalumab will be an infusion of 0.9% sodium chloride in place of active durvalumab. Patients will attend clinic visits on D1, D2, D8, D15, D16 and D22 of each cycle prior to receiving treatment. Safety bloods will be collected on Day 1, D8, D16 and D22 and will be reviewed prior to drug administration.
Sponsors
Warpnine Incorporated
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have histologically confirmed locally advanced pancreatic ductal adenocarcinoma 2. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent must be obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 3. Age > 18 years at time of study entry, age > 20 years for Japanese patients. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 5. Have either adequate archival tissue from prior biopsy for biomarker evaluation or willingness to undergo biopsy before treatment starts and willing to have biopsy during treatment at 12 weeks (if appropriate) 6. Have a negative serum pregnancy test (if a premenopausal female subject). Men and women of child-bearing potential must be willing to use effective contraceptive methods during the study, Section 9.1.5. 7. Adequate normal organ and marrow function as defined below: a. Haemoglobin greater than or equal to 9.0 g/dL b. Absolute neutrophil count (ANC) greater than or equal to 1.5 × 10^9 /L c. Platelet count greater than or equal to 100 × 10^9/L d. Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN). e. AST (SGOT)/ALT (SGPT) less than or equal to 3 x institutional upper limit of normal. f. Measured creatinine clearance (CL) >60ml/min/1.73 m2 or calculated creatinine Cl >40mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance. 8. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 9. Must have a life expectancy of at least 12 weeks 10. Have no clinically significant abnormalities on urinalysis. 11. Have acceptable coagulation status: a. Prothrombin time (PT) within normal limits b. Partial Thromboplastin Time (PTT) within normal limits 12. At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumour assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomisation. Must be eligible for treatment with nab-paclitaxel and gemcitabine
Exclusion criteria
1. Have received any prior chemotherapy, immunotherapy, or any other investigational agents for the treatment of pancreatic cancer 2. Concurrent enrolment in another clinical study, unless it is an observational (non- interventional) clinical study or during the follow-up period of an interventional study 3. Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. 4. History of allogenic organ transplantation. 5. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). 6. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 7. History of another primary malignancy 8. History of leptomeningeal carcinomatosis 9. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) greater than or equal to 470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) Regardless of whether this criteria stays or not, all patients should have a baseline ECG 10. History of active primary immunodeficiency 11. Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HbsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HbsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 12. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies. 13. Known to have active tuberculosis 14. Have a history of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on baseline chest CT scan. 15. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. 16. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP
Outcome results
None listed