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Trial registered on ANZCTR


Registration number
ACTRN12613001013752
Ethics application status
Approved
Date submitted
10/09/2013
Date registered
11/09/2013
Date last updated
23/07/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Phase I open label trial of Abraxane (nab-paclitaxel) administered concurrently with radiotherapy in patients with locally advanced inoperable pancreatic adenocarcinoma.
Scientific title
Phase I open label trial of Abraxane (nab-paclitaxel) administered concurrently with radiotherapy in patients with locally advanced inoperable pancreatic adenocarcinoma.
Secondary ID [1] 283185 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ART in LAP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients with locally advanced inoperable pancreatic adenocarcinoma 290043 0
Condition category
Condition code
Cancer 290422 290422 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
For each Cohort, on a weekly schedule (Day 1, 8, 15, 22, 29, 36) patients will receive a single dose of Abraxane (nab-paclitaxel) via intravenous infusion over 30 mins. These weekly doses will continue until maximum tolerated dose (MTD) is reached.
The first dose on Day 1 is followed up concurrently 24 hours later with radiotherapy, which is fractionated daily (1.8 Gy daily dose) from Day 2-5, Day 8-12, Day 15-19, Day 22-26, Day 29-33, Day 36-40, & Day 43. (5 fractions per week, 28 fractionated doses total), for up to 6 weeks only (if doses are tolerated).


Cohort 1: 25 mg/m2 - weekly dose / 6 weeks.

Cohort 2: 50 mg/m2 - weekly dose / 6 weeks.

Cohort 3: 75 mg/m2 - weekly dose / 6 weeks.

Cohort 4: 100 mg/m2 - weekly dose / 6 weeks.
Intervention code [1] 287912 0
Treatment: Drugs
Intervention code [2] 287918 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290448 0
To determine the maximum tolerated dose (MTD) of concurrent Abraxane (Registered Trademark) and external beam radiotherapy (EBRT) for inoperable locally advanced pancreatic cancer (LAPC).

When a dose-limiting toxicity is observed in any of the cohorts, up to three additional patients will be added to the cohort. If fewer than two of six patients in the cohort develop dose-limiting toxicity, escalation to the next cohort will proceed.
The maximum tolerated dose (MTD) will be the dose below highest dose level at which fewer than two of six patients experience dose-limiting toxicity.
Timepoint [1] 290448 0
Measured from Enrolment, until completion of Cohort 4 (dependent on limiting toxicities).
Secondary outcome [1] 304537 0
To evaluate the safety and tolerability of Abraxane (Registered Trademark) used concurrently with EBRT.
Timepoint [1] 304537 0
Patients will be assessed weekly from Day 1, looking for any toxicity from the treatment and graded according to CTCAE v4.0

on completion of chemotherapy (i.e. Day 36), a follow-up assessment will occur, then again 14 days after, and then 2 monthly for 1 year, 3 monthly for year 2, 4 monthly for year 3, 6monthly for year 4 – 5 years.
Secondary outcome [2] 304538 0
To evaluate the efficacy of Abraxane (Registered Trademark) used concurrently with EBRT (response rate, duration of response, progression free survival, median and 1- year overall survival) in LAPC
Timepoint [2] 304538 0
on completion of chemotherapy (i.e. Day 36), a follow-up assessment will occur, then again 14 days after, and then 2 monthly for 1 year, 3 monthly for year 2, 4 monthly for year 3, 6monthly for year 4 – 5 years.

Patients will be followed up from enrolment for disease progression and death to assess for exploratory endpoints of progression free survival, 1-year survival and overall survival. This will be assessed both clinically, biochemically (tumour markers), and radiologically.

Eligibility
Key inclusion criteria
1. Histologically or cytologically confirmed adenocarcinoma of the pancreas
2. Locally advanced disease not amenable to curative surgery.
3. Patients should have a projected life expectancy of at least 6 weeks
4. Complete recovery from prior surgery
5. ECOG performance status (less than or equal to) 2
6. Male or female, eighteen years or older
7. Measurable disease as defined by RECIST 1.1.
8. A glomerular filtration rate (GFR) (greater than or equal to) 60 mL/min as measured by TcDTPA scan or Cockroft-Gault equation
9. Serum bilirubin < 30 umol/L
10. Adequate bone marrow function, WBC > 3 x 10^9/L, neutrophils > 1.5 x 10^9/L, platelets > 100 x 10^9/L
11. Written informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Metastatic disease from pancreatic cancer
2. Prior chemotherapy
3. History of other malignant diseases other than non-melanomatous skin cancer or in-situ carcinoma of the uterine cervix
4. Clinical evidence of uncontrolled angina pectoris, cardiac failure, clinically significant cardiac arrhythmia, or other serious uncontrolled medical condition
5. Pregnant or lactating (any woman of childbearing potential must have a pregnancy test prior to randomisation and must take adequate precautions to prevent pregnancy during treatment)
6. Peripheral neuropathy greater than CTCAE Grade 2.
7. Hepatitis B positive (positive HBsAg / HBeAg)

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)
Patients will be recruited from consecutive referrals on a standard 3 + 3 dose escalation design.
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
Other
Other design features
Standard 3 + 3 dose escalation design. The dose escalation is continued until the predefined number of dose limiting toxicites is reached.
Phase
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The MTD can be determined without statistical analysis. The toxicity will be reviewed as the frequency of adverse events as a percentage. We will look at the data for trends in toxicity with dose escalation, however the sample sizes will be too small for meaningful comparisons. We look at efficacy data with response rates as percentages, survival data with progression free survival, overall survival, and 1-year survival with Kaplan-Meir Curves and calculation of hazard ratios. The data will be analysed for all patients who receive at least one dose of Abraxane (Registered Trademark) and one fraction of radiotherapy with an intention-to-treat model. No interim analysis is planned.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 1497 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 1498 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 1499 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 7338 0
5042 - Bedford Park
Recruitment postcode(s) [2] 7339 0
5011 - Woodville
Recruitment postcode(s) [3] 7340 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 287932 0
Commercial sector/Industry
Name [1] 287932 0
Drug is provided by Specialised Therapeutics Australia Pty Ltd. who is also providing a research grant of $2,000.00 per patient to assist sites with data administration costs.
Address [1] 287932 0
Specialised Therapeutics Australia
Level 1, 711 High Street
(PO Box 250)
East Kew, Victoria 3102, Australia
Country [1] 287932 0
Australia
Primary sponsor type
Government body
Name
Southern Adelaide Local Health Network
Address
Flinders Medical Centre
Flinders Drive
Bedford Park SA 5042
Country
Australia
Secondary sponsor category [1] 286656 0
None
Name [1] 286656 0
Address [1] 286656 0
Country [1] 286656 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289861 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 289861 0
Flinders Medical Centre
The Flats G5 - Rooms 3 & 4
Flinders Drive
Bedford Park SA 5042
Ethics committee country [1] 289861 0
Australia
Date submitted for ethics approval [1] 289861 0
20/03/2012
Approval date [1] 289861 0
20/05/2012
Ethics approval number [1] 289861 0
EC00188

Summary
Brief summary
In this study we plan to evaluate the maximum tolerated dose (MTD) of the drug Abraxane, which can be safely given to patients concurrently with radiotherapy in locally advanced pancreatic cancer (LAPC). Who is it for? You may be eligible to join this study if you are aged 18 years or above, and have been diagnosed with locally advanced adenocarcinoma of the pancreas, which is not amenable to curative surgery. Study details Participants in this study will receive the chemotherapy drug Abraxane (nab-paclitaxel) by intravenous infusion (i.e. directly into the vein) over 30 minutes on a weekly schedule, concurrently with radiotherapy for 6 weeks. The first participants will receive Abraxane at a dose of 25 mg/m2 and if this is tolerated the dose will be increased for the subsequent groups until the maximum tolerated dose can be determined. Participants will be regularly monitored for safety and tolerability throughout treatment. On completion of treatment they will also be followed up for up to 5 years in order to evaluate efficacy of treatment in terms of disease response and survival.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 42822 0
A/Prof Chris Karapetis
Address 42822 0
Flinders Centre for Innovation in Cancer
Flinders Medical Centre
Flinders Drive, Bedford Park SA 5042
Country 42822 0
Australia
Phone 42822 0
+61 8 8204 8997
Fax 42822 0
+61 8 8204 4997
Email 42822 0
c.karapetis@flinders.edu.au
Contact person for public queries
Name 42823 0
Ms Alison Richards
Address 42823 0
Level 2
Flinders Centre for Innovation in Cancer
Flinders Medical Centre
Flinders Drive, Bedford Park SA 5042
Country 42823 0
Australia
Phone 42823 0
+61 8 8204 6200
Fax 42823 0
+61 8 8204 4765
Email 42823 0
alison.richards@health.sa.gov.au
Contact person for scientific queries
Name 42824 0
A/Prof Chris Karapetis
Address 42824 0
Flinders Centre for Innovation in Cancer
Flinders Medical Centre
Flinders Drive, Bedford Park SA 5042
Country 42824 0
Australia
Phone 42824 0
+61 8 8204 8997
Fax 42824 0
+61 8 8204 4997
Email 42824 0
c.karapetis@flinders.edu.au

No data has been provided for results reporting
Summary results
Not applicable