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Trial registered on ANZCTR


Registration number
ACTRN12610001047088
Ethics application status
Approved
Date submitted
23/11/2010
Date registered
30/11/2010
Date last updated
30/01/2019
Date data sharing statement initially provided
30/01/2019
Date results provided
30/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised phase II study evaluating potential predictive biomarkers in the treatment of locally advanced and metastatic pancreatic cancer
Scientific title
A randomised phase II study evaluating potential predictive biomarkers and examining the efficacy and safety of oxaliplatin, 5-fluorouracil and leucovorin (as mFOLFOX6) compared to gemcitabine in the treatment of metastatic pancreatic cancer.
Secondary ID [1] 253047 0
Nil
Universal Trial Number (UTN)
Trial acronym
PAN1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally advanced and metastatic pancreatic cancer 258463 0
Condition category
Condition code
Cancer 258625 258625 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients randomised to the intervention arm will receive modified FOLFOX6 chemotherapy (mFOLFOX6). Each cycle of mFOLFOX6 will consist of:

- Oxaliplatin 85mg/m2 given as an intravenous (IV) infusion on day 1 of a 2 week cycle.
- 5-Flurouracil 400mg/m2 given as an IV infusion on day 1 of a 2 week cycle.
- Leucovorin 400mg/m2 given as an IV infusion on day 1 of a 2 week cycle.
- 5-Flurouracil 2400mg/m2 given as an IV continuous infusion over 46 hours, commencing on day 1 of a 2 week cycle.

The cycle will be repeated every 2 weeks.

Patients will continue their assigned treatment until progression, unacceptable toxicity or any of the reasons listed in protocol section 4.4.
Intervention code [1] 257452 0
Treatment: Drugs
Comparator / control treatment
Patients randomised to the control arm will receive gemcitabine chemotherapy. Each cycle of gemcitabine will consist of:


- Gemcitabine 1000mg/m2 given as an IV infusion on days 1, 8, 15 of a 4 week cycle.

The cycle will be repeated every 4 weeks.

Patients will continue their assigned treatment until progression, unacceptable toxicity or any of the reasons listed in protocol section 4.4.
Control group
Active

Outcomes
Primary outcome [1] 259614 0
Progression free survival at 4 months
Timepoint [1] 259614 0
Progression free survival is measured as the interval between randomisation and documented evidence of disease progression, the occurrence of new disease or death from any cause. Disease progression will be defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria and assessed every 8 weeks until progression.
Secondary outcome [1] 266414 0
Efficacy/activity of gemcitabine and FOLFOX as assessed by:
- Overall survival
- Time to progression
- Response rate according to RECIST v1.1
- CA19.9 response
Timepoint [1] 266414 0
- Overall survival time is measured as the time from the date of randomisation to the date of death due to any cause. Overall survival time will be censored at the date of the last follow-up visit for patients who are still alive.

- Time to documented disease progression is defined as the time from randomisation to the first date of documented disease progression or the occurrence of new disease. Disease progression will be defined by RECIST v1.1 criteria and assessed every 8 weeks until disease progression.

- Response rate according to RECIST v1.1. A tumour responder is defined as any patient exhibiting a best study response of complete response or partial response (based on computed tomography scan (CT scan)). Response will be assessed every 8 weeks until disease progression.

- CA19.9 will be assessed at baseline and 4 weekly from the start of treatment. CA19.9 response will be analysed as an exploratory endpoint using the following definition:
1. To be evaluable for response by CA19.9 requires 1 pre-treatment sample > twice the upper limit of normal in the absence of biliary obstruction, and at least 1 further sample after the start of treatment.
2. A response to CA19.9 has occurred if there is at least a 20% reduction in levels following the start of chemotherapy.
3. The date of response by CA19.9 is the date of the first sample with a 20% fall.
4. Documentation of any proven or suspected interval biliary sepsis or stenting is required for correlation.
Secondary outcome [2] 266415 0
Proportion of patients for whom a hENT1 result is obtained within a clinically useful timeframe.
Timepoint [2] 266415 0
Tissue samples for hENT1 testing will be collected prior to randomisation.
Secondary outcome [3] 266416 0
Progression free survival in each biomarker cohort.
Timepoint [3] 266416 0
Progression free survival is measured as the interval between randomisation and documented evidence of disease progression, the occurrence of new disease or death from any cause. Disease progression will be defined by RECIST v1.1 criteria and assessed every 8 weeks until progression.
Secondary outcome [4] 266417 0
To collect and analyse data from patient biospecimens
Timepoint [4] 266417 0
Tissue samples will be collected at baseline
Secondary outcome [5] 266418 0
Treatment related toxicity in each chemotherapy group
Timepoint [5] 266418 0
Toxicity will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 at baseline, prior to starting each chemotherapy cycle, at end of treatment and 30 days after the last study drug administration.
Secondary outcome [6] 266419 0
Ascertain if there is a relationship between biomarker status and treatment related toxicity
Timepoint [6] 266419 0
Toxicity will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) criteria v4.0 at baseline, prior to starting each chemotherapy cycle, at end of treatment and 30 days after the last study drug administration.
Secondary outcome [7] 266420 0
Establish a tissue bank from patients treated with and without gemcitabine to support further biomarker studies
Timepoint [7] 266420 0
Tissue samples will be collected at baseline

Eligibility
Key inclusion criteria
1. Males or females with radiologically and histologically confirmed metastatic pancreatic adenocarcinoma. Eligibility of patients with suspected disease must be confirmed by core biopsy prior to randomisation.
2. Adult patients; 18 years or over.
3. No previous treatment, except:
a. If adjuvant systemic therapy was received following resection, study entry is permissible if disease recurrence has occurred at least 6 months after completion of chemotherapy.
b. Previous radiotherapy is permissible if disease progression has occurred outside the radiotherapy field and disease recurrence has occurred at least 6 months after completion of radiotherapy.
c. Previous chemoradiotherapy is permissible if only radiosensitiser dose chemotherapy was used and disease progression has occurred outside of the radiotherapy field at least 6 months after completion of treatment.
4. Informed consent for all trial procedures, including:
a. Consent to undergo core biopsy to obtain tissue for biomarker analysis unless suitable archived paraffin embedded tissue (e.g. surgical specimen) is already available for human equilibrative nucleoside transporter 1 (hENT1) testing and other planned translational studies.
b. Consent for collection of peripheral blood for pharmacogenomic/pharmacogenetic analysis.
5. World Health Organisation (WHO) performance status 0-2.
6. Adequate renal, hepatic and haematological function, defined as;
a. Creatinine clearance (Cockcroft-Gault formula) >60mL/min
b. Bilirubin <1.5 x Upper Limit of Normal (ULN), aspartate aminotransferase (AST) + alanine aminotransferase (ALT) <3.0 x ULN (or <5.0 x ULN with documented liver metastases)
c. Haemoglobin >100 g/L, Platelets >150 x109/L and Neutrophils >1.5x 109/L
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous systemic treatment for metastatic pancreatic cancer.
2. Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures.
3. Other active malignancy or primary malignancy diagnosed within the previous 5 years, except for treated squamous or basal cell carcinoma of skin or cervical carcinoma.
4. Previous reactions to or suspected hypersensitivity to any of the investigational agents.
5. Peripheral neuropathy of any cause, of grade 2 or worse by CTCAE v4.0 criteria.
6. Seropositive for (Human Immunodeficiency Virus) HIV or Hepatitis C.
7. Active Hepatitis B not suppressed with antiviral treatment.
8. Symptomatic coronary or cardiac insufficiency.
9. History of thromboembolism, myocardial infarction or cardiovascular accident within preceding 3 months. Patients who have experienced deep venous thrombosis or pulmonary embolism within previous 6 months must be maintained on therapeutic levels of anticoagulation.
10. Diarrhoea >grade 2 and/or uncontrolled diarrhoea.

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)
Patients will be randomised to one of the two treatment arms in a 1:1 ratio using the minimisation method and stratified according to Locally advanced vs metastatic disease; Previous adjuvant chemotherapy (yes vs no); WHO performance status (0, 1 vs 2); and Institution.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/03/2011
Actual
17/04/2012
Date of last participant enrolment
Anticipated
Actual
8/02/2013
Date of last data collection
Anticipated
Actual
16/05/2014
Sample size
Target
80
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
NSW,VIC,ACT,QLD,SA,WA,TAS
Recruitment outside Australia
Country [1] 2985 0
New Zealand
State/province [1] 2985 0

Funding & Sponsors
Funding source category [1] 257906 0
Other Collaborative groups
Name [1] 257906 0
Australasian Gastrointestinal Trials Group (AGITG)
Country [1] 257906 0
Australia
Funding source category [2] 284711 0
Charities/Societies/Foundations
Name [2] 284711 0
Avner Nahmani Pancreatic Cancer Research Fund
Country [2] 284711 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Gastrointestinal Trials Group (AGITG)
Address
AGITG Coordinating Centre
Locked Bag 77
Camperdown
NSW 1450
Country
Australia
Secondary sponsor category [1] 257102 0
None
Name [1] 257102 0
Address [1] 257102 0
Country [1] 257102 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260102 0
Cancer Institute NSW Clinical Research Ethics Committee
Ethics committee address [1] 260102 0
Ethics committee country [1] 260102 0
Australia
Date submitted for ethics approval [1] 260102 0
08/11/2010
Approval date [1] 260102 0
24/01/2011
Ethics approval number [1] 260102 0
2010C/11/145
Ethics committee name [2] 298469 0
SLHD Ethics Review Committee (RPAH Zone)
Ethics committee address [2] 298469 0
Ethics committee country [2] 298469 0
Australia
Date submitted for ethics approval [2] 298469 0
22/10/2013
Approval date [2] 298469 0
14/11/2013
Ethics approval number [2] 298469 0
X13-0182 and HREC/13/RPAH/420

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

Contacts
Principal investigator
Name 31813 0
Dr Yu Jo Chua c/- PAN1 Trial Coordinator
Address 31813 0
NHMRC Clinical Trials Centre, Locked Bag 77, Camperdown NSW 1450
Country 31813 0
Australia
Phone 31813 0
+61 2 9562 5000
Fax 31813 0
Email 31813 0
[email protected]
Contact person for public queries
Name 15060 0
PAN1 Trial Coordinator
Address 15060 0
NHMRC Clinical Trials Centre, Locked Bag 77, Camperdown NSW 1450
Country 15060 0
Australia
Phone 15060 0
+61 2 9562 5000
Fax 15060 0
Email 15060 0
[email protected]
Contact person for scientific queries
Name 5988 0
PAN1 Trial Coordinator
Address 5988 0
NHMRC Clinical Trials Centre, Locked Bag 77, Camperdown NSW 1450
Country 5988 0
Australia
Phone 5988 0
+61 2 9562 5000
Fax 5988 0
Email 5988 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No plans have been made to share this participant data.


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.