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Trial registered on ANZCTR


Registration number
ACTRN12611000245998
Ethics application status
Approved
Date submitted
2/03/2011
Date registered
7/03/2011
Date last updated
27/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase II trial of panitumumab, cisplatin and gemcitabine in biliary tract cancer.
Scientific title
Phase II trial to evaluate the potential molecular profile of biliary tract cancer and also examine the clinical benefit and safety of panitumumab, cisplatin and gemcitabine in the treatment of biliary tract cancer
Secondary ID [1] 259677 0
AG0309BT
Universal Trial Number (UTN)
U1111-1119-6004
Trial acronym
TACTIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biliary Tract Cancer 261245 0
Condition category
Condition code
Cancer 259394 259394 0 0
Biliary tree (gall bladder and bile duct)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients recruited to the study will receive the following:

Panitumumab 9mg/kg IV, Day 1 of each cycle
Cisplatin 25mg/m2 IV, Day 1 and 8
Gemcitabine 1000mg/m2 IV, Day 1 and 8

Treatment is ongoing until disease progression, unacceptable toxicity, investigator discretion or patient request to cease.

Once off study treatment, patients will be followed-up 30 days after the last study drug administration, then every 12 weeks until disease progression (if patient had come off treatment for reasons other than progression) or commences new treatment.
Intervention code [1] 258108 0
Treatment: Drugs
Comparator / control treatment
Not applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 262253 0
Objective clinical benefit (combined rates of documented CR, PR and SD)
Timepoint [1] 262253 0
Objective clinical benefit (OCB) is the combined rate of confirmed complete response, partial response and stable disease as per RECIST v1.1 at 12 weeks.
Secondary outcome [1] 273400 0
Response rate by RECIST v1.1. criteria
Timepoint [1] 273400 0
A tumour responder is defined as any patient exhibiting a best study response of CR or PR (based on CT or MRI) as per RECIST v1.1. Scans taken every 6weeks from baseline
Secondary outcome [2] 273401 0
Time to treatment failure
Timepoint [2] 273401 0
Time to treatment failure is defined as the time from the date of study enrolment to the date of the first of the following events: early discontinuation of study therapy, progression of disease, or death due to any cause. Time to treatment failure will be censored at the date of the last follow-up visit for patients who did not discontinue early, who are still alive, and who have not progressed. Patients who did not receive any treatment will be censored on the day of enrolment.
Secondary outcome [3] 273402 0
Progression free survival
Timepoint [3] 273402 0
Time to documented disease progression is defined as the time from the date of study enrolment to the first date of documented disease progression, the occurrence of new disease or death. Patients who are still alive at the time of analysis and who have not had documented disease progression, will be censored at the date of the last clinical assessment, tumour assessment, or enrolment, whichever is the later. Patients who withdraw from treatment for reasons other than progression and who receive subsequent chemotherapy before progression will be considered to be censored at the time of commencement of subsequent therapy.
Secondary outcome [4] 273403 0
Overall survival
Timepoint [4] 273403 0
Overall survival time is defined as the time from the date of study enrolment 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.
Secondary outcome [5] 273404 0
Duration of response
Timepoint [5] 273404 0
Among responders, the duration of response is measured from the date of first documentation of response until the first date of documented disease progression or death due to any cause. Duration of tumour response will be censored at the date of the last follow-up visit for responders who are still alive and have not progressed.
Secondary outcome [6] 273405 0
CA19.9 response
Timepoint [6] 273405 0
1.The definition of CA19.9 response to be used in this study is based on that proposed for CA125 in ovarian cancer.
2.To be evaluable for response by CA19.9 requires 2 pre-treatment samples > twice the upper limit of normal, and at least 2 further samples after the start of treatment.
3.A response to CA19-9 has occurred if after two elevated levels prior to therapy there is at least a 50% fall which is confirmed by a fourth sample.
4.The two pre-treatment samples must both be > twice the upper limit of normal and at least one week but not more than three months apart. At least one of the samples should be within 1 week of starting treatment.
5.The third sample must be < 50% of the second sample.
6.The confirmatory fourth sample must be > 42 days after sample 3 and < 110% of sample 3.
7.Any intervening samples between samples 2 and 3 and between samples 3 and 4 must be < 110% of the previous sample unless considered to be rising due to tumour lysis.
8.The date of response by CA 19-9 is the date of the first sample with a 50% fall (3rd sample).
9.Documentation of any proven or suspected interval biliary sepsis or stenting is required for correlation
Secondary outcome [7] 273406 0
Quality of life
Timepoint [7] 273406 0
The quality of life will be assessed using QLQ-C30 and QLQ-Pan26. The EORTC QLQ-Pan26 is a self-administered cancer specific questionnaire with multi-dimensional scales. Questionaires will be completed up to 7 days before commencement of treatment, before the commencement of each cycle, after the last cycle and 6 weekly until disease progression.

Eligibility
Key inclusion criteria
1.Histologic or cytologic diagnosis of adenocarcinoma of the gallbladder or intra/extrahepatic bile ducts with locally advanced or metastatic disease (at study entry) that is not amenable to curative surgical resection or with recurrent disease after prior surgical resection or radiotherapy;
2.K-RAS wild-type oncogene;
3.Uni-dimensional measurable disease as assessed by CT scan (RECIST v1.1 criteria).
4.Patients must have received no prior chemotherapy or biological therapy for advanced disease;
5.Prior radiotherapy must be completed at least 4 weeks before study enrolment. Patients must have recovered from the acute toxic effects of the treatment prior to study enrolment;
6.WHO performance status 0, 1 or 2;
7.Estimated life expectancy of at least 12 weeks;
8.Patient compliance and geographic proximity that allows adequate follow-up;
9.Adequate organ function including the following:
a.Adequate bone marrow reserve: absolute neutrophil count (ANC) of greater than or equal to 1.5 x109/L, platelet count of greater than or equal to 100 x109/L, and haemoglobin of greater than or equal to 9 g/dL.
b.Hepatic: AST and ALT less than 5 x upper limit of normal (ULN); bilirubin less than 2 x ULN; in patients with obstructive jaundice and bilirubin greater than or equal 2 x ULN, internal or external biliary drainage should be performed before enrollment. Patients should be enrolled only if bilirubin declines to greater than or equal 2 x ULN.
c.Renal: creatinine less than 1. 5 x ULN and calculated creatinine clearance greater than or equal to 50 mL/min, calculated according to the Cockcroft formula.
10.Signed informed consent from patient or legal representative.
11.Patients available to complete study requirements (visits, tests, evaluations and follow-up procedures) in a timely manner.
12.Male and female patients with reproductive potential must use a reliable contraceptive method if appropriate (eg, intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after the study. Females with childbearing potential must have a negative urine pregnancy test within 7 days prior to study enrolment.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Medical or psychiatric conditions that compromise the patient’s ability to give informed consent or comply with the study protocol;
2.Heart failure, angina pectoris or arrhythmia that are poorly controlled in spite of medication or acute myocardial infarction within 6 months preceding study enrollment;
3.Active infection that in the opinion of the investigator would compromise the patient’s ability to tolerate therapy, especially uncontrolled biliary tract infections;
4.Poorly controlled diabetes mellitus;
5.Interstitial lung disease
6.Any other serious concomitant disorders that would compromise the safety of the patient or compromise the patient’s ability to complete the study, at the discretion of the investigator;
7.Pregnancy or breast feeding or unwilling / unable to practice adequate contraception
8.Second primary malignancy (except in situ carcinoma of the cervix or adequately treated non-melanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence)
9.Pregnancy or breast feeding or unwilling / unable to practice adequate contraception.
10.Documented brain metastasis.

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)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Multi-centre, phase II study
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 10493 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 10494 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 10495 0
Concord Repatriation Hospital - Concord
Recruitment hospital [4] 10496 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [5] 10497 0
St George Hospital - Kogarah
Recruitment hospital [6] 10498 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [7] 10499 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [8] 10500 0
Nepean Hospital - Kingswood
Recruitment hospital [9] 10501 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [10] 10502 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [11] 10503 0
Western Hospital - Footscray - Footscray
Recruitment hospital [12] 10504 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [13] 10505 0
The Townsville Hospital - Douglas
Recruitment hospital [14] 10506 0
Nambour General Hospital - Nambour
Recruitment hospital [15] 10507 0
HOCA @ Wesley - Auchenflower
Recruitment hospital [16] 10508 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [17] 10509 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 22207 0
2050 - Camperdown
Recruitment postcode(s) [2] 22208 0
2031 - Randwick
Recruitment postcode(s) [3] 22209 0
2139 - Concord
Recruitment postcode(s) [4] 22210 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 22211 0
2217 - Kogarah
Recruitment postcode(s) [6] 22212 0
2500 - Wollongong
Recruitment postcode(s) [7] 22213 0
2485 - Tweed Heads
Recruitment postcode(s) [8] 22214 0
2747 - Kingswood
Recruitment postcode(s) [9] 22215 0
3000 - Melbourne
Recruitment postcode(s) [10] 22216 0
3065 - Fitzroy
Recruitment postcode(s) [11] 22217 0
3011 - Footscray
Recruitment postcode(s) [12] 22218 0
3084 - Heidelberg
Recruitment postcode(s) [13] 22219 0
4814 - Douglas
Recruitment postcode(s) [14] 22220 0
4560 - Nambour
Recruitment postcode(s) [15] 22221 0
4066 - Auchenflower
Recruitment postcode(s) [16] 22222 0
5042 - Bedford Park
Recruitment postcode(s) [17] 22223 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 264599 0
Other Collaborative groups
Name [1] 264599 0
Australasian Gastrointestinal Trials Group (AGITG)
Address [1] 264599 0
Medical Foundation Building
University of Sydney
Level 6 92-94 Parramatta Road
Camperdown NSW 2050
Country [1] 264599 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Gastrointestinal Trials Group (AGITG)
Address
Medical Foundation Building
University of Sydney
Level 4 92-94 Parramatta Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 263738 0
None
Name [1] 263738 0
Address [1] 263738 0
Country [1] 263738 0
Other collaborator category [1] 251848 0
University
Name [1] 251848 0
NHMRC Clinical Trials Centre
Address [1] 251848 0
Medical Foundation Building
University of Sydney
92-94 Parramatta Road
Camperdown NSW 2050
Country [1] 251848 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260594 0
Cancer Institute NSW CLinical Research Ethics Committee
Ethics committee address [1] 260594 0
PO Box 41
Alexandria NSW 1435
Ethics committee country [1] 260594 0
Australia
Date submitted for ethics approval [1] 260594 0
14/03/2011
Approval date [1] 260594 0
08/06/2011
Ethics approval number [1] 260594 0
2011C/04/160

Summary
Brief summary
This study aims to evaluate the safety and efficacy of combining panitumumab with the standard cisplatin and gemcitabine treatment for advanced biliary tract cancer.

Who is it for?
You may be eligible to join this study if you are 18 years or above and have been diagnosed with biliary tract cancer. You should have locally advanced or metastatic disease that is not suitable for removal by surgery OR disease which has come back after previous surgical treatment or radiotherapy.
It has been shown that in other cancer types, panitumumab may be less likely to have an effect if the cancer cells have any mutation detected in a particular gene. That gene is known as KRAS.
As part of screening for this study, you will be asked to consent to a test to find out whether your cancer cells have a KRAS mutation. If you consent, cells taken from a previous diagnostic procedure will be sent to a central lab for the KRAS test. Only patients with cancer that does not have any mutation in the KRAS gene can participate in this study.

Trial details
The patient population that may participate in this trial would routinely be treated with a combination of the chemotherapy drugs gemcitabine and cisplatin. Participants in this study will additionally receive panitumumab; so that the outcomes associated with treatment using the 3 drugs together can be evaluated.
Participants will be monitored closely for side effects (toxicity) and for tumour response to treatment. Treatment will continue until disease progression, unacceptable toxicity, investigator discretion or patient request to cease. Once off study treatment, participants will be followed up for 30 days, then every 12 weeks until disease progression or commencement of new treatment, then according to best practice until death.

Data from this trial can inform us about how safe and tolerable the treatment is, and we can make some comparisons to other trials of chemotherapy alone for this disease. If positive, this study may lead to improved treatment for patients with biliary tract cancer. If negative, it will still give information regarding the biology of the disease, including the incidence of KRAS mutation in this tumour type.
Trial website
www.gicancer.org
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32270 0
Dr Jennifer Shannon
Address 32270 0
Nepean Hospital
Nepean Cancer Care Centre
Cnr of Somerset St and Great Western Highway
Kingswood NSW 2747
Country 32270 0
Australia
Phone 32270 0
+61 2 47 7343500
Fax 32270 0
Email 32270 0
Jenny.Shannon@health.nsw.gov.au
Contact person for public queries
Name 15517 0
Ms TACTIC Coordinator
Address 15517 0
NHMRC Clinical Trials Centre
The University of Sydney
Locked Bag 77
Camperdown 2050
Country 15517 0
Australia
Phone 15517 0
+61 2 9562 5000
Fax 15517 0
Email 15517 0
tactic@ctc.usyd.edu.au
Contact person for scientific queries
Name 6445 0
Dr Dr Jenny Shannon
Address 6445 0
NHMRC Clinical Trials Centre
The University of Sydney
Locked Bag 77
Camperdown 2050
Country 6445 0
Australia
Phone 6445 0
+61 2 9562 5000
Fax 6445 0
Email 6445 0
tactic@ctc.usyd.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 1168 0
Ferraro D, Goldstein D, O'Connell R.L, Zalcberg J.R, Sjoquist K.M, Tebbutt N.C, Grimison P, McLachlan S, Lipton S.S, Vasey P, Gebski V.J, Aiken C, Cronk M, Ng S, Karapetis C.S, Shannon J. on behalf of the Australasian Gastro-intestinal Trials Group. TACTIC: A multicenter, open-label, single-arm phase II trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer. Cancer Chemotherapy and Pharmacology DOI 10.1007/s00280-016-3089-4
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary