Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000109202
Ethics application status
Approved
Date submitted
21/01/2009
Date registered
17/02/2009
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 weekly docetaxel, cisplatin, fluoropyrimidine (wTCF) plus or minus panitumumab in advanced oesophago-gastric cancer.
Scientific title
ATTAX 3:A randomised phase II study evaluating weekly docetaxel, cisplatin, fluoropyrimidine (wTCF) plus or minus panitumumab in advanced oesophago-gastric cancer to evaluate response.
Secondary ID [1] 785 0
The Australasian Gastro-Intestinal Trials Group (AGITG) Protocol No: AG0607OG
Universal Trial Number (UTN)
Trial acronym
ATTAX 3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic or locally recurrent oesophago-gastric cancer 4218 0
Condition category
Condition code
Cancer 4435 4435 0 0
Oesophageal (gullet)
Cancer 4436 4436 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1: TCF Regimen
Docetaxel (T): 30 mg/m2 Calculated to the nearest mg and administered as an intravenous (IV) infusion on day 1 and day 8 of each cycle
Cisplatin (C):60 mg/m2 administered as an intravenous (IV) infusion on day 1 of each cycle.
Peripheral Venous Infusion (PVI) 5 - Fluorouracil (5FU) : 160 mg/m2 daily, by continuous infusion administered via an indwelling venous line [Peripherally Inserted Central Catheter (PICC)] line or infusaport according to local practice)
Or
Capecitabine: 500 mg/m2 Oral twice daily for 21 days (42 doses)

Group 2: TCF regimen (as above) + Panitumumab
Pantiumumab: Administered intravenously (IV) by an infusion pump through a peripheral line or indwelling catheter 9mg/kg on day 1

Treatment described above will continue for a maximum total of 8 cycles ([1 cycle=3 weeks] x 8 cycles) which equates to 24 weeks.
Intervention code [1] 3934 0
Treatment: Drugs
Comparator / control treatment
Group 1: TCF Regimen (weekly docetaxel, cisplatin, fluoropyrimidine) without panitumumab.
Control group
Active

Outcomes
Primary outcome [1] 5316 0
To evaluate the response rates of wTCF given with or without panitumumab in the treatment of patients with metastatic or locally recurrent oesophago-gastric cancer.
Timepoint [1] 5316 0
Treatment will continue for 24 weeks and tumour response will be assessed according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1) guidelines. Assessments will be carried out every 6 weeks during treatment and 12 weekly thereafter until disease progression, and then according to best-practice until death.
Secondary outcome [1] 9149 0
Overall survival
Timepoint [1] 9149 0
Overall survival will be measured from the date of patient entry to the date of death from any cause. Following completion of study treatment, patients will be followed up every 12 weeks until death.
Secondary outcome [2] 9150 0
Progression-free survival
Timepoint [2] 9150 0
Progression-free survival is measured from the date of patient randomisation to the study date of first evidence of disease progression or patient death. Disease progression will be defined by the RECIST v1.1 criteria every 6 weeks on study and 12 weekly from the end of study treatment (in follow up) until progression.
Secondary outcome [3] 9151 0
Treatment related toxicity
Timepoint [3] 9151 0
Toxicities will be recorded as adverse events on the Adverse Event case report form and must be graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, with the exception of skin- or nail-related toxicities, which must be graded using CTAE version 3.0 with modifications (Appendix 7 in study protocol). Adverse events will be assessed at baseline and at every cycle (every 3 weeks). A safety visit will be performed at 4 weeks +/- 7 days after the last study drug administration. In addition, every effort should be made to obtain blood for urea and electrolyte measurement, 8 weeks +/- 3 days after the last study drug administration.
Secondary outcome [4] 9152 0
Disease associated symptoms
Timepoint [4] 9152 0
Disease associated symptoms will be dervived from Quality of Life (QoL) questionnaires which will be completed 3 weekly for the first 12 weeks, then 6 weekly for the next 12 weeks, then 12 weekly until disease progression.
Secondary outcome [5] 9153 0
Quality of life during treatment.
Timepoint [5] 9153 0
Quality of life will be rated by EORTC QLQ-C30 together with the oesophageal specific module (OES18) or the gastric module (STO22) according to their primary tumour site. Patients with tumours involving the OGJ will complete the oesophageal module. Questionnaires will be completed 3 weekly for the first 12 weeks, then 6 weekly for the next 12 weeks, then 12 weekly until disease progression.

Eligibility
Key inclusion criteria
a) Age over 18.
b) Histological diagnosis of metastatic or locally recurrent oesophago-gastric cancer (squamous cell, adenocarcinoma or undifferentiated carcinoma)
c) Any primary oesophago-gastric site (oesophagus, oesophago-gastric junction (OGJ) or stomach)
d) Unidimensional measurable disease as assessed by computed tomography (CT) scan (RECIST v1.1 criteria). There must be at least one lesion > or equal to 20mm as measured by conventional computed tomography (CT) scan or > or equal to 10mm as measured by spiral computed tomography (CT) scan. All sites of disease must have been evaluated within 21 days of initiating study treatment and diagnosed by the investigator.
e) Prior palliative radiotherapy is allowed provided no concurrent chemotherapy was administered, all radiation toxicities have resolved to grade 1 or less and at least 14 days has elapsed from the last dose of radiotherapy until the start of chemotherapy in ATTAX 3. Furthermore, the site(s) of measurable disease must include at least one that is outside the radiation field unless this site has demonstrated clear progression, prior to randomisation.
f) World Health Organisation (WHO) performance status 0, 1 or 2 (Patients who ahave a performance status (PS) 2 should have serum albumin >30 g/L)
g) Able to swallow tablets if planned to receive capecitabine
h) Adequate bone marrow function with platelets>100x109/L; neutrophils>1.5x109/L and haemoglobin = 9.0g/dL.
i) Adequate renal function, with calculated creatinine clearance >50 ml/min based on the Cockcroft-Gault method. Adequate renal function (measured creatinine clearance>50ml/min) assessed by 24 hour urine or glomerular filtration rate (GFR) scan is also acceptable in cases where the Cockcroft-Gault method is considered inaccurate.
j) Adequate electrolytes, with serum magnesium level within the normal range and corrected serum calcium within the normal range.
k) Adequate hepatic function with serum total bilirubin <1.25 x upper limit of normal range and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <2.5x upper limit of normal range and alkaline phosphatase <5x upper limit of normal range
l) Life expectancy of at least 12 weeks
m) Negative pregnancy test and adequate contraceptive precautions if relevant
n) Written informed consent for main study AND tissue banking
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) Medical or psychiatric conditions that compromise the patient’s ability to give informed consent or comply with the study protocol.
b) Previous malignant disease other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix or other cancers treated with curative intent > 2 years previously and without evidence of relapse.
c) Uncontrolled metastatic disease to the central nervous system. Central Nervous System (CNS) metastases should be treated with surgery and/or radiotherapy and the patient should have stable neurology on a stable dose of steroids for at least 2 weeks.
d) Concomitant treatment with brivudine, lamivudine, ribavirin or any other nucleoside analogues.
e) Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g. cetuximab) or treatment with small molecule epidermal growth factor receptor (EGFR) inhibitors (e.g. erlotinib).
f) Prior chemotherapy agents for metastatic or recurrent disease. Neoadjuvant or adjuvant chemotherapy given alone or with concurrent radiotherapy > 12 months ago for oesophago-gastric cancer is allowed.
g) History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline computed tomography (CT) chest scan.
h) Known dihydropyrimidine dehydrogenase (DPD) deficiency.
i) Pregnancy or breast feeding (All women of childbearing potential must have a negative pregnancy test prior to inclusion into the trial).
j) Men or women of childbearing potential (women who are post-menopausal < 52 weeks, not surgically sterilised, or not abstinent) not consenting to use adequate contraception (per institutional standard of care) during the study and after the last investigational product (s) administration (24 weeks for women, 4 weeks for men).
k) Clinical evidence of >grade 2 peripheral neuropathy, ie. affecting activities of daily living
l) Any uncontrolled concurrent medical condition
m) Patients with known malabsorption syndromes (if planning to receive capecitabine).
n) Known allergy to the investigational product, to any of its excipients, to monoclonal antibodies, or to any of the components of the chemotherapy regimen
o) Any co-morbid disease that would increase risk of toxicity
p) Participation in any investigational drug study within the previous 4 weeks

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)
Randomisation will be carried out by site staff via a web based randomisation system.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomised to receive one of the two treatment regimens using the method of minimisation, stratified by primary tumour site, histology (adenocarcinoma vs squamous), WHO performance status (0-1 vs 2) use of 5FU vs capecitabine 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
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/03/2010
Actual
12/04/2010
Date of last participant enrolment
Anticipated
Actual
8/11/2011
Date of last data collection
Anticipated
Actual
12/12/2012
Sample size
Target
100
Accrual to date
Final
77
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,SA,WA,TAS
Recruitment postcode(s) [1] 1490 0
2145
Recruitment postcode(s) [2] 1491 0
2031
Recruitment postcode(s) [3] 1492 0
3002
Recruitment postcode(s) [4] 1493 0
5042
Recruitment postcode(s) [5] 1494 0
7001
Recruitment postcode(s) [6] 1495 0
3690
Recruitment postcode(s) [7] 1496 0
2065
Recruitment postcode(s) [8] 1497 0
6000
Recruitment postcode(s) [9] 1498 0
2200
Recruitment postcode(s) [10] 1499 0
2747
Recruitment postcode(s) [11] 1500 0
3084
Recruitment postcode(s) [12] 1501 0
3199
Recruitment postcode(s) [13] 1502 0
5000
Recruitment postcode(s) [14] 1503 0
4810
Recruitment postcode(s) [15] 1504 0
5011
Recruitment postcode(s) [16] 1505 0
3165
Recruitment outside Australia
Country [1] 1542 0
New Zealand
State/province [1] 1542 0
Christchurch

Funding & Sponsors
Funding source category [1] 4399 0
Other Collaborative groups
Name [1] 4399 0
AGITG -Australasian Gastro-Intestinal Group
Country [1] 4399 0
Australia
Primary sponsor type
Other Collaborative groups
Name
AGITG -Australasian Gastro-Intestinal Group
Address
Locked Bag 77
Camperdown 1450
Country
Australia
Secondary sponsor category [1] 4065 0
None
Name [1] 4065 0
Address [1] 4065 0
Country [1] 4065 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6448 0
Cancer Institute NSW
Ethics committee address [1] 6448 0
Ethics committee country [1] 6448 0
Australia
Date submitted for ethics approval [1] 6448 0
31/03/2009
Approval date [1] 6448 0
30/06/2009
Ethics approval number [1] 6448 0
2009C/04/091

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

Contacts
Principal investigator
Name 35104 0
A/Prof Niall Tebutt
Address 35104 0
NHMRC CTC
Locked Bag 77
Camperdown 1450
Country 35104 0
Australia
Phone 35104 0
+61295625000
Fax 35104 0
Email 35104 0
[email protected]
Contact person for public queries
Name 12451 0
ATTAX 3 Trial Coordinator
Address 12451 0
NHMRC Clinical Trials Centre
Oncology Program Manager
Locked Bag 77
Camperdown 1450
Country 12451 0
Australia
Phone 12451 0
+61 2 9562 5000
Fax 12451 0
+61 2 95625094
Email 12451 0
[email protected]
Contact person for scientific queries
Name 3379 0
ATTAX 3 Trial Coordinator
Address 3379 0
NHMRC Clinical Trials Centre ATTAX 3 Trial Coordinator Locked Bag 77 Camperdown 1450
Country 3379 0
Australia
Phone 3379 0
+61 2 9562 5000
Fax 3379 0
+61 2 95625094
Email 3379 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
There are no plans at this stage to share this information.


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
SourceTitleYear of PublicationDOI
EmbaseMolecular-targeted first-line therapy for advanced gastric cancer.2016https://dx.doi.org/10.1002/14651858.CD011461.pub2
EmbaseFirst-line systemic therapy for advanced gastric cancer: a systematic review and network meta-analysis.2019https://dx.doi.org/10.1177/1758835919877726
N.B. These documents automatically identified may not have been verified by the study sponsor.