Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000061437
Ethics application status
Approved
Date submitted
6/11/2015
Date registered
21/01/2016
Date last updated
8/03/2021
Date data sharing statement initially provided
8/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
An International Multicentre Open Label Randomised Phase II Advanced Anal Cancer Trial Comparing Cisplatin plus 5-fluorouracil versus Carboplatin plus Weekly Paclitaxel in Patients with Inoperable Locally Recurrent or Metastatic Disease
Scientific title
A phase II trial comparing cisplatin plus 5-fluorouracil versus carboplatin plus weekly paclitaxel in patients with inoperable locally recurrent or metastatic anal cancer to demonstrate which is more effective and less toxic for patients with this disease.
Secondary ID [1] 287616 0
AG0214ANL
Secondary ID [2] 288238 0
NCT02051868
Universal Trial Number (UTN)
Trial acronym
InterAACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Squamous Cell Carcinoma of the Anus 296423 0
Condition category
Condition code
Cancer 296687 296687 0 0
Bowel - Anal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Those randomised to the experimental arm will receive 6 cycles of chemotherapy within a 4 weekly schedule as follows:
Paclitaxel 80 mg/m2 as a 1-hour i.v. infusion on day 1,8 and 15 of each cycle followed by carboplatin 1-hour (or 30-min) i.v. infusion to an AUC of 5 on day 1, with the
initial dose calculated according to the Calvert formula (mg = [glomerular
filtration rate (GFR) + 25] x 5). The GFR used in the Calvert formula to calculate
AUC-based dosing should not exceed 125 ml/min.
Intervention code [1] 293010 0
Treatment: Drugs
Comparator / control treatment
Participants randomised to the control arm will receive 8 cycles of chemotherapy within a 3 weekly schedule as follows:
Cisplatin 60 mg/m2 by iv infusion on day 1
5-Fluorouracil 1000 mg/m2/day - days 1-4 by continuous 24 hour iv infusion
Control group
Active

Outcomes
Primary outcome [1] 296294 0
To evaluate best overall response rate (ORR) by 24 weeks post treatment in the cisplatin plus 5-fluorouracil (5-FU) arm versus the carboplatin plus weekly paclitaxel arm
Timepoint [1] 296294 0
Best overall response rate is defined as the percentage of patients achieving confirmed partial or complete responses as per RECIST v1.1 by 24 weeks post treatment start in the modified intention to treat population
Secondary outcome [1] 318096 0
Progression-free survival
Timepoint [1] 318096 0
PFS will be analysed once all patients have been followed up for at least 12 months post treatment start. This is calculated from the date of randomisation to the date of confirmed clinical/radiological progression or death from any cause. Patients who are lost to follow-up, withdraw from follow-up or alive and progression free will be censored at the date of last follow-up.
Secondary outcome [2] 318097 0
Overall survival
Timepoint [2] 318097 0
Overall survival will be analysed once all patients have been followed up for at least 12 months post treatment start. This is calculated from the date of randomisation to the date of death from any cause. Patients, in whom no death is recorded, will be censored at the date they were last seen alive.
Secondary outcome [3] 318098 0
Disease control rate (DCR) (stable disease (SD) or better) at 12 and 24 weeks
Timepoint [3] 318098 0
12 and 24 weeks post treatment start. Disease control rate is defined as complete response, partial response or stable disease, and will be assessed in accordance with the RECIST criteria v1.1. in the mITT and ITT population.
Secondary outcome [4] 318099 0
Best overall response rate of non-irradiated lesions
Timepoint [4] 318099 0
24 weeks post treatment start. Best overall response of non-irradiated lesions is defined as the percentage of patients achieving confirmed partial response or complete response as per RECIST v1.1 of non-irradiated sites of disease in the ITT population in the mITT population.
Secondary outcome [5] 318100 0
Anti-tumour activity and magnitude of response as captured by waterfall plot analyses. Anti-tumour activity will be assessed by imaging (CT or MRI).
Timepoint [5] 318100 0
Anti-tumour activity and magnitude of response will be captured by waterfall plot analyses in the mITT population and indicate the percentage change in tumour size from baseline to the time of best response. Imaging (CT or MRI) will be performed at baseline and after 12 and 24 weeks of study treatment. In case the study treatment is continued for more than 24 weeks, tumour response will be assessed every 12 weeks.
Secondary outcome [6] 318101 0
Toxicity
Timepoint [6] 318101 0
Toxicity will be analysed once all patients have been followed up for at least 4 weeks post treatment completion. Toxicity will be graded according to the NCI CTCAE Version 4.0
Secondary outcome [7] 318102 0
Quality of Life
Timepoint [7] 318102 0
3 years. Quality of Life will be evaluated using the EORTC QLQ C30 and EQ-5D-5L questionnaires. The functional and symptomatic scales and global health status from the QLQ C30 and EQ-5D-5L questionnaire will be calculated as per EORTC and EuroQol guidelines, respectively.
Secondary outcome [8] 318103 0
Feasibility of conducting a multicentre, international study on squamous cell carcinoma of the anus and recruiting within a reasonable time frame.
Timepoint [8] 318103 0
3 years. The study will be conducted in approximately 50 international centres. This secondary endpoint will be measured by (i) the proportion of centres that successfully recruit at least one patient and (ii) overall recruitment rate. We anticipate and would be able to confirm feasibility if 80% of the centres fully engaged with the study. The aim would be to recruit 80 patients in 36 months (10 by month 6, 20 by month 12, 50 by month 24 and 80 by month 36).

Eligibility
Key inclusion criteria
-Inoperable, locally recurrent or metastatic disease (tumour resectability should be assessed by a local surgeon or Multidisciplinary Team)
-Histological or cytological confirmation of epidermoid anal carcinoma (includes squamous, basaloid and cloacogenic lesions) from the primary tumour or a newly diagnosed recurrent/metastatic lesion.
-Age greater than or equal to 18 years.
-ECOG PS less than or equal to 2.
-Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1.
-Previous definitive chemo-radiation is permitted for early stage tumours (cisplatin-based chemo-radiation is permitted but only if tumour progression/relapse occurs after 6 months from treatment completion).
-Previous systemic chemotherapy is permitted if administered as induction treatment (less than or equal to 2 cycles) before definitive chemoradiotherapy for early stage disease and there is no evidence of tumour progression during or after treatment completion.
-HIV positive patients will be considered eligible if they are on HAART and have a CD4 count of greater than or equal to 200/microlitre (HIV+ patients who are on HAART and have a CD4 count less than 200/microlitre are eligible if the plasma viral load is below the level of detection according to the local assay).
-Adequate cardiac and respiratory function; absolute neutrophil count (ANC) greater than or equal to 1.5x109/l; platelets greater than or equal to 100x109/l; haemoglobin (Hb) greater than or equal to 9g/dl for males and greater than or equal to 8g/dl for females; creatinine clearance greater than or equal to 50ml/minute; serum bilirubin less than or equal to 1.5x upper limit of normal (ULN); alanine transaminase (ALT) or aspartate transaminase (AST) less than or equal 3x ULN (If liver metastases are present, serum transaminases less than or equal 5x ULN are permitted.
-Fertile men and women must agree to take adequate contraceptive precautions during, and for at least six months after therapy.
-Life expectancy of at least 3 months.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Tumours of adenocarcinoma, melanoma, small cell and basal cell histology are excluded.
-Newly diagnosed locally advanced tumour which requires upfront systemic chemotherapy but is still amenable to curative treatment (i.e. chemotherapy followed by definitive chemoradiotherapy)
-Locally recurrent tumour which is amenable to curative resection (as deemed by a local surgeon or Multidisciplinary Team).
-Tumour relapse/progression within 6 months of completion of a cisplatin-based chemoradiotherapy regimen for the treatment of early stage tumours.
-Previous administration of greater than 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease.
Tumour progression during or immediately after completion of less than or equal to 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease.
-Previous use of systemic chemotherapy or other investigational drugs for the treatment of inoperable locally recurrent or metastatic tumours (previous use of radiotherapy in this setting is not an exclusion criterion if: 1) non-irradiated target tumour lesions are present at randomisation for the purpose of tumour response assessment or 2) in the absence of non-irradiated target tumour lesions, progression of the irradiated tumour lesions according to the RECIST criteria version 1.1 is documented).
-Current or recent (within 30 days of first study dosing) treatment with another investigational drug or participation in another investigational study.
-Documented or symptomatic brain metastases and/or central nervous system metastases or leptomeningeal disease.
-Major surgery performed less than 28 days from treatment start.
-Palliative radiotherapy completed less than or equal to 7 days from treatment start.
-Clinically significant (i.e. active) cardiac disease (e.g. symptomatic coronary artery disease, uncontrolled cardiac arrhythmia, or myocardial infarction within the last 6 months). Any history of clinically significant cardiac failure.
- History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan.
- HIV positive patients who are not on HAART or have a CD4 count of less than 200/microlitre in the presence of detectable plasma viral load according to the local assay.
-Known history of active hepatitis B or hepatitis C infection.
-Serious active infection requiring i.v. antibiotics at enrolment.
-Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
-Other clinically significant disease or co-morbidity that may adversely affect the safe delivery of treatment within this trial.
-Known hypersensitivity to any of the study drugs or excipients.
-Known peripheral neuropathy greater than grade 1 (absence of deep tendon reflexes as thesole neurological abnormality does not render the patient ineligible).
-Pre-existing hearing impairment.
-Patients planning for a live vaccine.
-Pregnant or lactating females.

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)
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 design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
29/02/2016
Actual
4/01/2017
Date of last participant enrolment
Anticipated
Actual
15/11/2017
Date of last data collection
Anticipated
31/01/2021
Actual
30/03/2018
Sample size
Target
90
Accrual to date
Final
91
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC
Recruitment hospital [1] 6273 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 6274 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 6275 0
Royal Hobart Hospital - Hobart
Recruitment hospital [4] 7064 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 13808 0
5042 - Bedford Park
Recruitment postcode(s) [2] 13809 0
2031 - Randwick
Recruitment postcode(s) [3] 13810 0
7000 - Hobart
Recruitment postcode(s) [4] 14792 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 7208 0
United Kingdom
State/province [1] 7208 0
Country [2] 7261 0
Denmark
State/province [2] 7261 0
Country [3] 7262 0
United States of America
State/province [3] 7262 0
Country [4] 7293 0
Norway
State/province [4] 7293 0

Funding & Sponsors
Funding source category [1] 292197 0
Other Collaborative groups
Name [1] 292197 0
Australasian Gastro-Intestinal Trials Group (AGITG)
Country [1] 292197 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Gastro-Intestinal Trials Group (AGITG)
Address
Locked Bag 77
Camperdown
NSW 1450
Country
Australia
Secondary sponsor category [1] 290874 0
Hospital
Name [1] 290874 0
The Royal Marsden NHS Foundation Trust
Address [1] 290874 0
Downs Road, Sutton, Surrey, SM2 5PT
United Kingdom
Country [1] 290874 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293687 0
Northern Sydney Local Health District Human Research Ethics Committee (NSLHD HREC)
Ethics committee address [1] 293687 0
Ethics committee country [1] 293687 0
Australia
Date submitted for ethics approval [1] 293687 0
24/11/2014
Approval date [1] 293687 0
29/06/2015
Ethics approval number [1] 293687 0
HREC/14/HAWKE/421

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

Contacts
Principal investigator
Name 60830 0
Dr Amitesh C Roy
Address 60830 0
NHMRC Clinical Trials Centre Locked Bag 77 Camperdown, NSW, 1450
Country 60830 0
Australia
Phone 60830 0
+61 2 9562 5000
Fax 60830 0
+61 2 9562 5094
Email 60830 0
[email protected]
Contact person for public queries
Name 60831 0
InterAACT Trial Coordinator
Address 60831 0
NHMCR CTC Locked Bag 77 Camperdown, NSW, 1450
Country 60831 0
Australia
Phone 60831 0
+61 2 9562 5000
Fax 60831 0
+61 2 9562 5094
Email 60831 0
[email protected]
Contact person for scientific queries
Name 60832 0
InterAACT Trial Coordinator
Address 60832 0
NHMCR CTC Locked Bag 77 Camperdown, NSW, 1450
Country 60832 0
Australia
Phone 60832 0
+61 2 9562 5000
Fax 60832 0
+61 2 9562 5094
Email 60832 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


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
No additional documents have been identified.