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Trial registered on ANZCTR


Registration number
ACTRN12623000223639
Ethics application status
Approved
Date submitted
16/02/2023
Date registered
2/03/2023
Date last updated
25/04/2024
Date data sharing statement initially provided
2/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A safety and early efficacy study of LSTA1 in combination with durvalumab, gemcitabine and nab-paclitaxel, as first-line treatment in locally advanced pancreatic ductal adenocarcinoma (PDAC)
Scientific title
A Phase 1 single-blind study evaluating LSTA1 in combination with durvalumab, gemcitabine and nab-paclitaxel as a first-line treatment in locally advanced pancreatic ductal adenocarcinoma (PDAC)
Secondary ID [1] 308990 0
Nil known
Universal Trial Number (UTN)
Trial acronym
iLSTA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 329018 0
Condition category
Condition code
Cancer 325998 325998 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 325432 0
Treatment: Drugs
Comparator / control treatment
Cohort 1: Control Group
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) + Placebo LSTA1 (3.2mg/kg over 1 minute +/-30 seconds; intravenously; D1, D2, D8, D15, 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.

Placebo LSTA1 and Placebo Durvalumab will be an infusion of 0.9% sodium chloride in place of active LSTA1 and durvalumab.
Control group
Active

Outcomes
Primary outcome [1] 333854 0
To determine the safety and tolerability of the addition of LSTA1 when added to the combination of durvalumab, gemcitabine, and nab-paclitaxel in subjects with locally advanced pancreatic ductal adenocarcinomas.

Safety and tolerability will be tested by performing weekly blood tests (haematology and chemistry) and 8 weekly disease assessment (CT CAP and RECIST 1.1). Patients will be well informed of potential safety issues through the patient informed consent form. The study will utilise CTCAE V5.0 when assessing any adverse events experienced by the patient. The patients will also be reviewed by a trained and delegated study coordinator as well as the treating oncologist or trained sub-investigator at each clinic visit.

Toxicities to be monitored:
- Neutropenia (monitored with weekly blood tests)
- Thrombocytopenia (monitored with weekly blood tests)
- Febrile neutropenia (monitored with weekly blood tests and vital sign collection)
- Peripheral neuropathy (monitored through patient reporting of symptoms and weekly physical exams)
- Cutaneous toxicity (monitored through patient reporting of symptoms and weekly physical exams)
- Gastrointestinal toxicity (mucositis, diarrhoea) (monitored through patient reporting of symptoms and weekly physical exams)
- Myelotoxicity (monitored through patient reporting of symptoms and weekly physical exams)
- Sepsis (monitored through patient reporting of symptoms, weekly physical exams and weekly blood tests)
- Hepatotoxity (monitored with weekly blood tests)
- Thrombotic microangiopathy (monitored through patient reporting of symptoms and weekly blood tests)
- Pulmonary toxicity (monitored through patient reporting of symptoms, weekly physical exams and 8-weekly scans)
Timepoint [1] 333854 0
All adverse events and dose limiting toxicities will be summarized descriptively and assessed continuously from first dose through until 30 days after the last dose of trial drug or until resolution of AEs/toxicity. Patients will then be monitored by their treating oncologist for 5 years as standard of care.
Secondary outcome [1] 418485 0
1. The disease control rate (DCR) (complete response (CR) + partial response (PR) + stable disease (SD)) at 16-weeks.
This will be assessed using CT CAP imaging, RECIST 1.1 assessment, blood tests and tumour markers at baseline and every 8 weeks thereafter. Blood tests are at NATA accredited laboratories using standard measurements and all images are assessed by RECIST 1.1
Timepoint [1] 418485 0
1. Response assessments will be determined by performing 8-weekly imaging and Recist 1.1 at the 16-week time point, post-first dose.
Secondary outcome [2] 418809 0
2. The best overall response rate (ORR) (CR+PR) at 16-weeks.
This will be assessed using CT CAP imaging, RECIST 1.1 assessment, blood tests and tumour markers at baseline and every 8 weeks thereafter. Blood tests are at NATA accredited laboratories using standard measurements and all images are assessed by RECIST 1.1
Timepoint [2] 418809 0
2. Best overall response will be determined by reviewing each of the 8-weekly imaging and Recist 1.1 results at the 16-week time point, post-first dose..

Secondary outcome [3] 418810 0
3. Median progression-free survival (mPFS) and median progression-free survival (mPFS) at 6 months (mPFS 6 mo.).
Standard of care is to review of patients by the treating oncologist with blood tests, tumour markers and imaging every 3 months until either progression / recurrence or the patients achieves 5 years of disease free state. Blood tests are at NATA accredited laboratories using standard measurements and all images are assessed by RECIST1.1
Timepoint [3] 418810 0
3. Average PFS amongst the participants at the end of the study as well as 6 month time point, post-first dose. As per standard of care practice, patients will continue to be monitored for 5 years by their treating oncologist.
Secondary outcome [4] 418811 0
4. Median overall survival (mOS) and median overall survival 6 months (mPFS 6 mo.).

Standard of care is to review of patients by the treating oncologist with blood tests, tumour markers and imaging every 3 months until either progression / recurrence or the patients achieves 5 years of disease free state. Blood tests are at NATA accredited laboratories using standard measurements and all images are assessed by RECIST 1.1
Timepoint [4] 418811 0
4. Average OS amongst the participants at the end of the study as well as 6 month time point, post-first dose. As per standard of care practice, patients will continue to be monitored for 5 years by their treating oncologist.
Secondary outcome [5] 418812 0
5. Duration of response for responding patients with measurable disease at baseline.
This will be assessed using CT CAP imaging, RECIST 1.1 assessment, blood tests and tumour markers at baseline and every 8 weeks thereafter. Blood tests are at NATA accredited laboratories using standard measurements and all images are assessed by RECIST 1.1
Timepoint [5] 418812 0
5. Measured from the first timepoint where an objective response is determined until the last timepoint the patient is found to have an objective response. As per standard of care practice, patients will continue to be monitored for 5 years by their treating oncologist.
Secondary outcome [6] 418813 0
6. To determine levels of immune cell infiltration in tumour biopsies (pre-treatment and on-treatment at 12 weeks) in each cohort
Timepoint [6] 418813 0
6. Change in tumour infiltrating lymphocyte (TIL) score as measured by H&E TIL count according to Salgado criteria from pre-surgical biopsy to resected tumour specimen.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This study will enroll 30 participants randomised 4:1:1 in favour of the cohort 3 study intervention.
Data will be presented in a tabular form with mean and standard deviation or median with lowest and highest values and/or 95% confidence interval values. Analysis of the primary endpoint will be on a full population set basis.
Due to primary safety endpoint and small sample size this study will not be powered towards defined statistical significance.

The full analysis set will include all subjects who are randomised.

The safety population includes all subjects who took at least one dose of any trial medication.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
31/03/2023
Actual
3/04/2023
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
30
Accrual to date
17
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 24038 0
St John of God Hospital, Subiaco - Subiaco
Recruitment postcode(s) [1] 39534 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 313202 0
Charities/Societies/Foundations
Name [1] 313202 0
Warpnine Incorporated
Country [1] 313202 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Warpnine Incorporated
Address
35 Davenport Road. Booragoon, WA 6154
Country
Australia
Secondary sponsor category [1] 314919 0
None
Name [1] 314919 0
Address [1] 314919 0
Country [1] 314919 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312434 0
St John of God HREC
Ethics committee address [1] 312434 0
Ethics committee country [1] 312434 0
Australia
Date submitted for ethics approval [1] 312434 0
13/01/2023
Approval date [1] 312434 0
14/02/2023
Ethics approval number [1] 312434 0
1949

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 124654 0
Dr Andrew Dean
Address 124654 0
St John of God Subiaco Hospital. Suite C202, 12 Salvado Road, Subiaco WA 6008
Country 124654 0
Australia
Phone 124654 0
+61 8 9438 8554
Fax 124654 0
Email 124654 0
[email protected]
Contact person for public queries
Name 124655 0
Meg Croucher
Address 124655 0
Warpnine Incorporated: 35 Davenport Road, Booragoon, WA 6154
Country 124655 0
Australia
Phone 124655 0
+61 406 818 810
Fax 124655 0
Email 124655 0
[email protected]
Contact person for scientific queries
Name 124656 0
Meg Croucher
Address 124656 0
Warpnine Incorporated: 35 Davenport Road, Booragoon, WA 6154
Country 124656 0
Australia
Phone 124656 0
+61 406 818 810
Fax 124656 0
Email 124656 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial, after de-identification.
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
Case-by-case basis at the discretion of Primary Sponsor
Available for what types of analyses?
Any purpose
How or where can data be obtained?
Access subject to approvals by Principal Investigator: [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.