Trial registered on ANZCTR


Trial ID
ACTRN12611000848909
Ethics application status
Approved
Date submitted
8/08/2011
Date registered
10/08/2011
Date last updated
3/09/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
GAP: Phase II gemcitabine and nab-paclitaxel for resectable pancreas cancer
Scientific title
The effect of preoperative gemcitabine and nab-Paclitaxel compared to historical controls on RO surgical rate in patients with resectable pancreas cancer
Secondary ID [1] 262780 0
Nil
Universal Trial Number (UTN)
Trial acronym
GAP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Resectable pancreas cancer 270490 0
Condition category
Condition code
Cancer 270646 270646 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
2 pre-operative chemotherapy cycles with 1000mg/m2 gemcitabine and 125mg/m2 nab-paclitaxel given intravenously on day 1, day 8 and day 15 of a 28 day cycle. Patient will then undergo surgical resection of their pancreas cancer with curative intent. Patients will be allocated to receive different post surgical adjuvent treatment depending on their surgical outcome. R0 (complete resection) patients will recieve 4 further cycles of gemcitabine 1000mg/m2 and 125mg/m2 nab-paclitaxel as described above. R1 (incomplete resection) patients will receive 45Gy radiation in 20 fractions daily over 5 weeks in combination with continous infusion of 5FU 200mg/m2/day for the duration of the radiotherapy. This is then followed by 4 cycles of gemcitabine and nab-paclitaxel chemotherapy as described above OR chemotherapy as per R0 resection outcome group (at treating clinician's discretion)
Intervention code [1] 269123 0
Treatment: drugs
Comparator / control treatment
There will be no control as this is a single arm study looking at the affect of pre-operatve chemotherapy on the surgical resection outcome
Control group
Uncontrolled

Outcomes
Primary outcome [1] 269370 0
To evaluate R0 surgical resection rate in patients with resectable pancreatic cancer following pre-operative treatment with gemcitabine and nab-paclitaxel. (R0 resection rate).
This will be determined by histopathological examination at the study site with a determination made if there is any microscopic disease left after surgery (R0). This will later be centrally reviewed by a histopatholgoist as quality assurance (all patients will have their slides reviewed centrally).
Timepoint [1] 269370 0
After Surgery
Secondary outcome [1] 279471 0
To determine markers of response following pre-operative treatment of patients with resectable pancreatic cancer. (Ca19.9; CEA)
Timepoint [1] 279471 0
following pre-operative chemotherapy, 9 weeks following randomisation
Secondary outcome [2] 279472 0
To assess treatment efficacy via disease-free survival, patterns of relapse, loco-regional control and overall survival following treatment. (disease-free survival, disease relapse, loco-regional control and overall survival)
Timepoint [2] 279472 0
survival data will be collected for 12 months post treatment.
Secondary outcome [3] 279473 0
To assess treatment morbidity. (e.g. rates of pancreatic leak, stent occlusion, sepsis, hospital re-admission rates , chemotherapy and radiotherapy toxicity)
Timepoint [3] 279473 0
AE data collected at each study visit.
Secondary outcome [4] 287538 0
To assess feasibility of planned chemotherapy/ chemoradiotherapy (proportions of patients starting and finishing > 80% of the planned doses of chemotherapy / chemoradiotherapy pre and post-operatively; dose delays, dose reductions and dose intensity of chemotherapy).
Timepoint [4] 287538 0
data will be collected at each cycle throughout treatment.
Secondary outcome [5] 287539 0
To assess feasibility of planned surgery (proportion of patients completing all three planned treatments)
Timepoint [5] 287539 0
Data will be collected at each cycle throughout treatment
Secondary outcome [6] 287540 0
To assess the impact of this regimen on the quality of life with particular focus on the impact of pre-operative chemotherapy, the impact of surgery on quality of life and degree of recovery time.
Timepoint [6] 287540 0
QOL scores determined before and after pre-operative chemotherapy, QOL scores after surgery compared to 12 months post-operatively

Eligibility
Key inclusion criteria
-Males or females with histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the pancreas. In those patients with histology or cytology highly suspicious for adenocarcinoma, the diagnosis of pancreatic adenocarcinoma will be made by integrating this histological data with the clinical and radiographic data (tumour mass visible on three phase CT scan (or MRI scan) of the pancreas). Patients with islet cell neoplasms are excluded;
-Disease is clearly resectable on the basis of physical examination and the following objective CT criteria (or MRI if indicated):
(i) no evidence of extra-pancreatic disease;
(ii) no evidence of tumour abutment of the superior mesenteric artery (SMA) or coeliac axis (T4); and
(iii) no evidence of portal vein infiltration of more than 180 degrees of the circumference or occlusion of the superior mesenteric vein (SMV) or SMV–portal vein (PTV) confluence.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patient considered to have a borderline resectable tumour.
- Patients with locally advanced disease.
- Evidence of systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude surgery, chemotherapy or chemoradiotherapy.
- Concurrent illness including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.

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 registered before recieving the pre-operative chemotherapy with gemcitabine and nab-paclitaxel. after 2 cycles patients will undergo surgery to remove their cancer. Depending on surgical out come the patients will either be allocated to recieve a further 4 cycle of the chemotherapy (R0) or radiochemotherapy (radation in combination with 5-FU) followed by 4 cycles of chemotherapy with gemcitabine and nab-paclitaxel.
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)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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
Current
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,ACT,QLD,SA,WA

Funding & Sponsors
Funding source category [1] 269601 0
Other Collaborative groups
Name [1] 269601 0
Australasian Gastro-Intestinal Trials Group (AGITG)
Address [1] 269601 0
GI CANCER Institute
Medical Foundation Building
University of Sydney
Level 6 92-94 Parramatta Road
Camperdown NSW 2050
Country [1] 269601 0
Australia
Funding source category [2] 284786 0
Other Collaborative groups
Name [2] 284786 0
Specialised Therapeutics Australia
Address [2] 284786 0
PO Box 250
East Kew, Victoria 3102, Australia
Country [2] 284786 0
Australia
Funding source category [3] 285537 0
Other Collaborative groups
Name [3] 285537 0
Specialised Therapeutics Australia
Address [3] 285537 0
PO Box 250
East Kew, Victoria 3102, Australia
Country [3] 285537 0
Australia
Primary sponsor type
Other Collaborative groups
Name
AGITG
Address
GI CANCER Institute
Medical Foundation Building
University of Sydney
Level 6 92-94 Parramatta Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 266638 0
None
Name [1] 266638 0
Address [1] 266638 0
Country [1] 266638 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269553 0
Cancer Institute NSW
Ethics committee address [1] 269553 0
Australian Technology Park
Level 9, 8 Central Avenue
EVELEIGH NSW 2015
AUSTRALIA
Ethics committee country [1] 269553 0
Australia
Date submitted for ethics approval [1] 269553 0
09/12/2012
Approval date [1] 269553 0
03/01/2013
Ethics approval number [1] 269553 0
2011C/09/169

Summary
Brief summary
This study aims to determine the effect of pre-operative chemotherapy in patients with resectable pancreatic cancer. Patients may be eligible to join this study if they are aged 18 years or more and have been diagnosed with cancer of the pancreas for which they plan to undergo surgery. All participants in this trial will undergo pre-operative chemotherapy with the drugs gemcitabine and nab-paclitaxel. The chemotherapy will be administered intravenously on day 1, day 8 and day 15 of a 28 day cycle. Patients will receive 2 cycles before undergoing surgery to remove their cancer. Participants will be assessed after surgery to determine whether all the cancerous tissue has been successfully removed. If all the cancer has been removed the patients will have another 4 cycles of chemotherapy with gemcitabine and nab-paclitaxel. If all the cancer is not removed during surgery, the treating clinician may decide that patients will receive radiotherapy everyday for 5 weeks, at the same time as receiving a continuous infusion of 5-flurouracil which will then be followed by 4 cycles of chemotherapy with gemcitabine and nab-paclitaxel. They may also decide to to treat patients with chemotherapy as described for patients who have had all their cancer removed. Blood tests and safety assessments will also be regularly conducted throughout the 12 month duration of the trial. The results from this study will be compared to previous data to determine whether pre-operative chemotherapy will improve resection, and thus, survival outcomes in patients with pancreatic cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32977 0
A/Prof Andrew Barbour
Address 32977 0
NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown, NSW 1450


Country 32977 0
Australia
Phone 32977 0
+61 2 9562 5000
Fax 32977 0
Email 32977 0
gap@ctc.usyd.edu.au
Contact person for public queries
Name 16224 0
Ms GAP trial coordinator
Address 16224 0
NHMRC Clinical Trails Centre
University of Sydney
Locked Bag 77
Camperdown
NSW
1450
Country 16224 0
Australia
Phone 16224 0
+61 2 9562 5000
Fax 16224 0
+61 2 9562 5094
Email 16224 0
gap@ctc.usyd.edu.au
Contact person for scientific queries
Name 7152 0
Ms GAP trial coordinator
Address 7152 0
NHMRC Clinical Trials Centre
University of Sydney
Locked Bag 77
Camperdown
NSW
1450
Country 7152 0
Australia
Phone 7152 0
+61 2 9562 5000
Fax 7152 0
+61 2 9562 5094
Email 7152 0
gap@ctc.usyd.edu.au