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Trial registered on ANZCTR


Registration number
ACTRN12614000676617
Ethics application status
Approved
Date submitted
17/06/2014
Date registered
26/06/2014
Date last updated
28/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Positron Emission Tomography (PET) scan in predicting response and survival in patients undergoing chemoradiation followed by surgery for oesophageal cancer
Scientific title
A prospective, single arm, multi-centre study of post neoadjuvant chemoradiation PET as predictor of pathological response in patients with localised oesophageal cancer
Secondary ID [1] 284789 0
nil known
Universal Trial Number (UTN)
U1111-1157-9772
Trial acronym
CROSS PET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
oesophageal carcinoma 292163 0
Condition category
Condition code
Cancer 292501 292501 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will receive chemotherapy consisting of carboplatin (AUC=2) and paclitaxel (50mg/m2)administered intravenously one day per week for 5 weeks. At the same time, radiotherapy will be given with a total dose of 41.4 Gy in 23 fractions, starting on the first day of the first chemotherapy cycle with 5 fractions per week over 4.5 weeks. PET scan will be performed 4 weeks after chemoradiation. Patients will be fasted for 4 hours before imaging and blood glucose level will be measured. Patients will be injected with a small amount of radioactive tracer fluorodeoxygluocose (FDG) and the PET scan will take place for about 45-90 minutes. Patients will undergo surgery 6 weeks after chemoradiation.

Intervention code [1] 289605 0
Diagnosis / Prognosis
Intervention code [2] 289657 0
Treatment: Drugs
Intervention code [3] 289658 0
Treatment: Other
Comparator / control treatment
none
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292382 0
To assess the predictive value of the post chemoradiation PET scan with pathological response after surgical resection (volumetric PET assessment)

PET scan is performed at week 9 (4 weeks post chemoradiation) and the sensitivity, specificity, positive and negative predictive values of PET will be calculated. Whilst PET data is the primary analysis, pathological assessment obtained from surgery at week 11 (6 weeks post chemoradiation) is used to examine the correlation of PET and pathological response.
Timepoint [1] 292382 0
week 9 (4 weeks post chemoradiation) for PET scan
week 11 (6 weeks post chemoradiation) for surgery
Secondary outcome [1] 308826 0
Pathological response (complete and near complete)
Assessed on the pathological specimen obtained from surgery
Timepoint [1] 308826 0
Week 6 post chemoradiation
Secondary outcome [2] 308828 0
Complete surgical resection (clear microscopic margin)
Assessed on the pathological specimen obtained from surgery
Timepoint [2] 308828 0
Week 6 post chemoradiation
Secondary outcome [3] 308829 0
Assessing treatment toxicity from chemoradiation (rates of adverse events)

For example,
Radiation-skin redness, fatique, temporary discomfort when swallowing, reflux symptoms
Chemotherapy-hypersensitivity reaction, low blood counts, infections

Assessed via clinical assessment and standard chemotherapy blood test
Timepoint [3] 308829 0
Clinic visits are scheduled at baseline, weeks 1, 3, 5 of chemoradiation, week 10 (5 weeks post chemoradiation), then every 3 months from date of surgery for 12 months, and then 6 monthly thereafter for up to 2 years
Secondary outcome [4] 308830 0
Disease free survival (disease progression or death)
Assessed via clinical assessment and ongoing follow-up
Timepoint [4] 308830 0
Clinic visits are scheduled at baseline, weeks 1, 3, 5 of chemoradiation, week 10 (5 weeks post chemoradiation) , then every 3 months from date of surgery for 12 months, and then 6 monthly thereafter for up to 2 years
Secondary outcome [5] 308831 0
Overall survial
Assessed via clinical assessment and ongoing follow-up
Timepoint [5] 308831 0
Clinic visits are scheduled at baseline, week 1, 3, 5 of chemoradiation, week 10 (5 weeks post chemoradiation), then every 3 months from date of surgery for 12 months, and then 6 monthly thereafter for up to 2 years
Secondary outcome [6] 308832 0
Quality of life before, during and after neoadjuvant chemoradiation
Measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer 30 (EORTC QLQ-C30) and Oesophago-gastric 25 (QLQ-OG25)
Timepoint [6] 308832 0
Quality of life questionnaires to be completed at baseline, week 1, 3, and 5 during chemoradiation, week 10 (5 weeks post chemoradiation), then every 3 months from date of surgery for 12 months, and then 6 monthly thereafter for up to 2 years

Eligibility
Key inclusion criteria
Age greater than or equal to 18 years

Surgically resectable carcinoma of oesophagus (PET staged T1-3, N0-1, M0)

No invasion of the tracheobronchial tree

Tumour must not extend greater than 2cm into the stomach

ECOG between 0 and 2

Patients must have adequate haematological, renal, hepatic, and pulmonary functions defined as: granulocytes greater than or equal to 1.5 x 10^9/L, platelets greater than or equal to 100 x 10^9/L, total bilirubin less than or equal to 1.5 x upper normal limit, and creatinine clearance greater than or equal to 50ml/min

Non-English speaking background patient is allowed as long as interpreter service is provided during the enrolment, treatment, and follow up phase
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Past or current history of malignancy other than entry diagnosis
-History of another malignancy within 5 years prior to registration. Participants with curatively treated cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or superficial bladder tumours (T1a[Non-invasive tumour], and Tis[Carcinoma in situ]), or participants who have been free of other malignancies for greater than or equal to 5 years prior to enrolment are eligible for this study

Previous chemotherapy or radiotherapy

Myocardial infarct in last 6 months

Congestive heart failure or uncontrolled arrhythmia

Neurotoxicity grade greater than 1


Uncontrolled diabetes mellitus despite maximum therapy

Pregnancy, lactation or inadequate contraception

Known allergic reaction to FDG PET contrast

Study design
Purpose of the study
Diagnosis
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)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis
Survival endpoints were calculated from the date of enrolment. OS and DFS were estimated using the Kaplan-Meier product limit method and will be displayed using Kaplan-Meier curves and median survivals

The level of significance of a series of prognostic factors in the prediction of survival endpoints was estimated using the log-rank test statistic. Cox regression analysis provided a multivariate analysis of these endpoints with selected prognostic factors

Continuous variables will be summarized using descriptive statistics e.g. number of patients, mean, median, standard deviation, minimum and maximum. Qualitative variables will be summarized by counts and percentages. Unless otherwise stated calculation of proportions will include the missing category. Longitudinal data will be illustrated where appropriate with graphics

Descriptive statistics of baseline patient characteristics and treatment received will be presented for all eligible patients

EORTC QLQ will be described according to EORTC guidelines. A descriptive analysis of Quality of Life (QoL) data over time will be undertaken. This will include identifying the most commonly reported, and the most troublesome, symptoms and side effects. Items from the questionnaires will be derived to form numerical scales in accordance with the scoring manuals and/or scoring conventions for each instrument. The applicability of repeated measures mixed modelling to the QoL scores collected longitudinally will be investigated. Appropriate methods for dealing with missing QoL data will be detailed in the statistical analysis plan and be informed by a blinded review of the data. Under certain assumptions, mixed models provide unbiased estimates as do multiple imputation techniques. Patterns of missing data will be considered to assess potential missing data mechanisms

A descriptive analysis of the adverse events (AE) data will be prepared for study participants. The number and percentage of participants who experience AEs will be tabulated according to AE name, organ class and grade. The number and percentage of participants who experience a grade 3 or 4 AE will also be tabulated, as will the number and percentage of participants who experience any grade AE. A descriptive analysis of dose interruption and dose modification rates will also be prepared

The 95% confidence intervals will be reported wherever appropriate

A study close-out date will be determined for the time to event analyses in order to prevent bias in the reporting of results. This is generally taken to be the earliest of the dates of last contact for patients still alive and not lost to follow-up. The event times of patients lost to follow up will be censored at the close-out date if the event has not previously occurred

Statistical analyses will be performed using STATA-SE v.11.0 (StataCorp LP, College Station, TX, USA)

A samples size of at least 184 patiens will be sufficient to exclude a false negative rate of 5% or higher (lower 95% for totaol concordance >0.95). Allowing for a modest number of drop outs and patients not proceeding to surgery, a total of 200 patients will be recruited.

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)
NSW
Recruitment hospital [1] 2629 0
St George Hospital - Kogarah
Recruitment hospital [2] 2630 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 2631 0
Westmead Hospital - Westmead
Recruitment hospital [4] 2632 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [5] 2633 0
Nepean Hospital - Kingswood
Recruitment hospital [6] 2634 0
Wollongong Hospital - Wollongong
Recruitment hospital [7] 2635 0
Liverpool Hospital - Liverpool
Recruitment hospital [8] 2636 0
Gosford Hospital - Gosford

Funding & Sponsors
Funding source category [1] 289420 0
Other Collaborative groups
Name [1] 289420 0
South Eastern Sydney Local Health District
Address [1] 289420 0
District Executive Unit, Level 4, The Sutherland Hospital & Community Health Service, Cnr The Kingsway & Kareena Road, CARINGBAH, NSW, 2229
Country [1] 289420 0
Australia
Primary sponsor type
Individual
Name
Dr Ariyanto Pramana
Address
Radiation Oncology Queensland Cairns
Liz Plummer Cancer Care Centre
Cnr Lake and Grove Sts
Cairns QLD 4870
Country
Australia
Secondary sponsor category [1] 288103 0
Individual
Name [1] 288103 0
Dr Yaw Chin
Address [1] 288103 0
Cancer Care Centre, St George Hospital, Gray Street, Kogarah NSW 2217
Country [1] 288103 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291178 0
South Eastern Local Health District
Ethics committee address [1] 291178 0
Room G71 East Wing, Edmund Blacket Building, Prince of Wales Hospital, Randwick NSW 2031
Ethics committee country [1] 291178 0
Australia
Date submitted for ethics approval [1] 291178 0
29/10/2013
Approval date [1] 291178 0
14/01/2014
Ethics approval number [1] 291178 0
13/220 (HREC/13/POWH/586)

Summary
Brief summary
This phase II study aims to investigate whether PET scan performed after the completion of chemotherapy and radiation can predict response of oesophageal cancer.
Who is it for ? You may be eligible to join this study if you are aged 18 years or more, have been diagnosed with a localised oesophageal cancer, and are suitable for chemotherapy combined with radiotherapy prior to surgery.
Study details: Participants will undergo a single additional PET scan 4 weeks after the completion of chemo-radiotherapy. Approximately 2 weeks following this they will undergo surgery. Specimens obtained from surgery will be used to evaluate the predictive value of the PET scan. Participants will be scheduled to clinic visits for follow-up at 5 weeks after chemo-radiotherapy, 3 monthly for the first 12 months, and then 6 monthly thereafter until a minimum of 2 years. At each visit, apart from routine history and physical examination, participants will be asked to complete a series of short questionnaires which evaluate the health-related quality of life. This is a prospective, single arm, multi-centre study and a total of 200 participants will be recruited.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49162 0
Dr Ariyanto Pramana
Address 49162 0
Radiation Oncology Queensland Cairns
Liz Plummer Cancer Care Centre
Cnr Lake and Grove Sts
Cairns QLD 4870
Country 49162 0
Australia
Phone 49162 0
+61 7 4036 5200
Fax 49162 0
+61 7 4036 5210
Email 49162 0
Ariyanto.Pramana@health.qld.gov.au
Contact person for public queries
Name 49163 0
Ms Dan Lu
Address 49163 0
Clinical Research Unit, Pitney Clinical Sciences Building, St George Hospital, Gray Street, Kogarah NSW 2217
Country 49163 0
Australia
Phone 49163 0
+61 2 9113 4825
Fax 49163 0
+ 61 2 9113 4822
Email 49163 0
Dan.Lu@sesiahs.health.nsw.gov.au
Contact person for scientific queries
Name 49164 0
Dr Yaw Chin
Address 49164 0
Cancer Care Centre
St George Hospital, Gray St, Kogarah NSW 2217
Country 49164 0
Australia
Phone 49164 0
+61 2 9113 3916
Fax 49164 0
Email 49164 0
Yaw.Chin@sesiahs.health.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
No Results