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Trial registered on ANZCTR


Registration number
ACTRN12621001347853
Ethics application status
Approved
Date submitted
30/08/2021
Date registered
7/10/2021
Date last updated
15/09/2024
Date data sharing statement initially provided
7/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical study assessing the anti-cancer activity of sulfasalazine in patients with advanced or metastatic pancreatic ductal adenocarcinoma whose cancer has worsened following therapy with current standard of care.
Scientific title
A phase 2, open-label, single-arm sulfasalazine monotherapy trial of progression-free survival in patients with pancreatic adenocarcinoma
Secondary ID [1] 305106 0
None
Universal Trial Number (UTN)
Trial acronym
SPEAR
Linked study record
ACTRN12616000908437
Participants in this trial will be referred from ACTRN12616000908437.

Health condition
Health condition(s) or problem(s) studied:
Pancreatic cancer 323344 0
Condition category
Condition code
Cancer 320917 320917 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be commenced on treatment with sulfasalazine (500mg oral tablets) at 1.5 g per day in three evenly divided doses. The dose will be incrementally increased to the target dose (4.5 g per day in three evenly divided doses), subject to tolerability. The dose may be further escalated to 6 g per day, in three evenly divided doses, subject to no significant intolerance and study PI approval.
Participant acetylator status, which affects how quickly sulfasalazine is processed in the body, is used to inform the dose escalation schedule during the first treatment cycle. For fast acetylators, the sulfasalazine dose is expected to increase to 3g per day on Day 4, further escalated to the target dose on Day 8 and may be further escalated to 6g per day on Day 15 subject to tolerability and PI approval. For slow acetylators, the dose is expected to increase to 3g per day on Day 8, further escalated to the target dose on Day 15 and may be further escalated to 6g per day on Day 22 subject to tolerability and PI approval.
All participants will continue the study treatment until clinical or radiological progression or until treatment discontinuation criteria are met. Tablet counts will be performed by the study team to assess adherence.
To prevent low levels of folic acid that can occur with sulfasalazine treatment, participants will also take 1mg of oral folic acid tablets daily.
Intervention code [1] 321519 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328707 0
To quantify progression-free survival (PFS) rate at 6 months among patients with pancreatic ductal adenocarcinoma treated with sulfasalazine. Disease progression is assessed by site investigators using Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 criteria using CT scans or clinical criteria based on clinical signs and symptoms. PFS is assessed by site investigators at study visits/contacts.
Timepoint [1] 328707 0
6 months from start date of study treatment
Secondary outcome [1] 400023 0
Objective tumour response rate as assessed by site investigators using CT scans and RECIST v1.1 criteria.
Timepoint [1] 400023 0
Every 8 weeks until disease progression and at disease progression
Secondary outcome [2] 400024 0
Median progression free survival. Disease progression is assessed by site investigators using Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 criteria for CT scans or clinical criteria based on clinical signs and symptoms. PFS is assessed by site investigators at study visits/contacts.
Timepoint [2] 400024 0
At the conclusion of the study
Secondary outcome [3] 400025 0
Clinical benefit rate (CBR) at 16 weeks as assessed using CT scans and RECIST v1.1 criteria.
Timepoint [3] 400025 0
16 weeks from start date of study treatment
Secondary outcome [4] 400026 0
Duration of clinical benefit (DCB) as assessed using CT scans and RECIST v1.1 criteria.
Timepoint [4] 400026 0
For the duration of the study
Secondary outcome [5] 400027 0
Overall survival rate at 12 months. Survival is assessed by site investigators at study visits/contacts.
Timepoint [5] 400027 0
12 months from start date of study treatment
Secondary outcome [6] 400028 0
Median overall survival. Survival is assessed by site investigators at study visits/contacts.
Timepoint [6] 400028 0
At the conclusion of the study
Secondary outcome [7] 400029 0
Time to progression. Disease progression is assessed by site investigators using Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 criteria for CT scans or clinical criteria based on clinical signs and symptoms. Survival is assessed at study visits/contacts.
Timepoint [7] 400029 0
Weekly during first cycle of treatment, at 2 week intervals during second cycle and then monthly for the duration of participant enrolment in the study
Secondary outcome [8] 400030 0
Median Growth Modulation Index
Timepoint [8] 400030 0
At the conclusion of the study
Secondary outcome [9] 400031 0
Safety of treatment as assessed at study visits/contacts using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Timepoint [9] 400031 0
Assessed at study visits until 30 days after discontinuation of study medication
Secondary outcome [10] 400032 0
Tolerability of treatment as assessed by the interruption of treatment due to toxicity. Toxicity is defined as as a treatment-related adverse event equal to or above Grade 3 as graded by CTCAE v5.0.
Timepoint [10] 400032 0
Assessed at study visits until discontinuation of study medication
Secondary outcome [11] 400033 0
Health-related quality of life (HRQOL) over the course of the trial
Timepoint [11] 400033 0
Assessed every 4 weeks until disease progression
Secondary outcome [12] 400034 0
Dose intensity achieved (mean, range and percentage of intended/target dose). The dose administered is assessed at study visits via tablet counts and review of the Participant Diary.
Timepoint [12] 400034 0
Assessed at each study visit until discontinuation of study medication
Secondary outcome [13] 400035 0
Median duration of objective tumour response as assessed using CT scans and RECIST v1.1 criteria.
Timepoint [13] 400035 0
At the conclusion of the study

Eligibility
Key inclusion criteria
1. Aged >=18 years old.
2. Histologically or cytologically confirmed locally advanced (Stage III) unresectable or metastatic (Stage IV) PDAC.
3. Adequate archival tissue for comprehensive genomic profiling.
4. Disease must have progressed after one-line of standard fluoropyrimidine- or gemcitabine-based chemotherapy for advanced disease. Treatment break within the upfront chemotherapy regimen is considered the same line of therapy and is permitted.
5. Have had one-line of systemic therapy for advanced disease. Patients who have had two lines of systemic therapy or are intolerant of second-line treatment may be eligible after consultation with the study Chief Investigators.
6. ECOG performance status score of 0-1.
7. Life expectancy >12 weeks.
8. Measurable disease as defined by RECIST version 1.1.
9. Presence of tumour amenable to a second biopsy.
10. Adequate haematological indices as defined by:
a. Absolute neutrophil count >=1.0 x 10^9/L
b. Haemoglobin >=100 g/L
c. Platelet count >=100 x 10^9/L
d. Bilirubin <1.5x ULN
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <1.5x ULN; or <5.0x ULN if liver metastases are present
f. International normalised ratio (INR) <1.3 in the absence of anticoagulation therapy.
11. Adequate renal function, as defined by Creatinine Clearance (CrCl) >=50mL/min using Cockcroft formula.
12. Women of childbearing potential and men must use effective contraception during the study and for at least 90 days after the last dose of study medication. Women of childbearing potential must have a negative screening serum pregnancy test.
13. Ability to adhere to the study visit schedule and understand and comply with all protocol requirements and instructions from study staff.
14. Provision of written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Diagnosis of other histology types other than ductal adenocarcinoma, including but not limited to pancreatic acinar cell carcinoma, well-differentiated neuroendocrine tumour, neuroendocrine carcinoma, or lymphoma. Mixed histology with predominantly adenocarcinoma component is eligible.
2. Uncontrolled diabetes, defined as HbA1c >10% in previous 3 weeks.
3. Pregnant or breastfeeding.
4. Major surgery within 28 days prior to Day 1. Biliary stent placement or endoscopic procedure is permitted.
5. Radiation therapy within 28 days prior to Day 1.
6. Uncontrolled central nervous system or brain metastases.
7. Uncontrolled hypertension (systolic blood pressure [SBP] >180mmHg or diastolic blood pressure [DBP] >105mmHg).
8. New York Heart Association Class III or IV congestive heart failure.
9. Current clinical or laboratory evidence of active or uncontrolled infection.
10. History of uncontrolled severe asthma or atopic dermatitis requiring hospitalization.
11. Concomitant advanced solid or haematological malignancy with an expected prognosis that is worse than the index pancreatic adenocarcinoma.
12. Active major gastrointestinal bleeding.
13. Known hypersensitivity or allergic reactions to salicylates or sulphonamide derivatives, including antibacterial sulphonamides, oral hypoglycaemics and thiazides.
14. Known intestinal or urinary obstruction or porphyria.
15. Participation in studies of investigational products within 28 days prior to Day 1, or 5 half-lives, whichever is longer.
16. Clinically significant and uncontrolled medical condition considered a high risk for participation in an investigational study or a likelihood that the potential participant will be unable to comply with protocol requirements and complete the trial (e.g. emphysema requiring supplemental oxygen, poorly controlled arrhythmia, psychiatric illness, Alzheimer's disease).
17. Current abuse of alcohol or drugs.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/09/2022
Actual
19/06/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
38
Accrual to date
27
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 23064 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 24460 0
Epworth Richmond - Richmond
Recruitment hospital [3] 25712 0
Blacktown Hospital - Blacktown
Recruitment hospital [4] 25713 0
Royal Hobart Hospital - Hobart
Recruitment hospital [5] 25714 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [6] 25715 0
The Northern Hospital - Epping
Recruitment hospital [7] 27098 0
Gold Coast University Hospital - Southport
Recruitment hospital [8] 27099 0
Sydney Adventist Hospital - Wahroonga
Recruitment postcode(s) [1] 38415 0
5000 - Adelaide
Recruitment postcode(s) [2] 40042 0
3121 - Richmond
Recruitment postcode(s) [3] 40043 0
3121 - Richmond
Recruitment postcode(s) [4] 41536 0
2148 - Blacktown
Recruitment postcode(s) [5] 41537 0
7000 - Hobart
Recruitment postcode(s) [6] 41538 0
2298 - Waratah
Recruitment postcode(s) [7] 41539 0
3076 - Epping
Recruitment postcode(s) [8] 43171 0
4215 - Southport
Recruitment postcode(s) [9] 43172 0
2076 - Wahroonga

Funding & Sponsors
Funding source category [1] 309499 0
Government body
Name [1] 309499 0
Cancer Institute NSW
Country [1] 309499 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Australian Genomic Cancer Medicine Centre Ltd t/a Omico
Address
Level 7, 370 Victoria Street
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 310477 0
None
Name [1] 310477 0
Address [1] 310477 0
Country [1] 310477 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309285 0
St Vincent’s Hospital HREC
Ethics committee address [1] 309285 0
Ethics committee country [1] 309285 0
Australia
Date submitted for ethics approval [1] 309285 0
30/08/2021
Approval date [1] 309285 0
29/09/2021
Ethics approval number [1] 309285 0
2021/ETH11214

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

Contacts
Principal investigator
Name 113626 0
Prof David Goldstein
Address 113626 0
Senior Staff Specialist
Medical Oncology, Nelune Comprehensive Cancer Centre
Prince of Wales Hospital
Corner of Avoca and High Street
Randwick, NSW 2031
Country 113626 0
Australia
Phone 113626 0
+61 2 9382 5105
Fax 113626 0
Email 113626 0
d.goldstein@unsw.edu.au
Contact person for public queries
Name 113627 0
Viral Gandhi / Vanessa Jones
Address 113627 0
The George Institute for Global Health
Level 18, International Towers 3, 300 Barangaroo Ave, Sydney NSW 2000
Country 113627 0
Australia
Phone 113627 0
+61 2 80524300
Fax 113627 0
Email 113627 0
SPEAR@georgeinstitute.org.au
Contact person for scientific queries
Name 113628 0
David Goldstein
Address 113628 0
Senior Staff Specialist
Medical Oncology, Nelune Comprehensive Cancer Centre
Prince of Wales Hospital
Corner of Avoca and High Street
Randwick, NSW 2031
Country 113628 0
Australia
Phone 113628 0
+61 2 9382 5105
Fax 113628 0
Email 113628 0
d.goldstein@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
There are no plans for this to occur at this time and participant consent will be required


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.