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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02051868




Registration number
NCT02051868
Ethics application status
Date submitted
13/01/2014
Date registered
31/01/2014
Date last updated
4/11/2015

Titles & IDs
Public title
International Multicentre Study in Advanced Anal Cancer Comparing Cisplatin Plus 5 FU vs Carboplatin Plus Weekly Paclitaxel
Scientific title
An International Multicentre Open Label Randomised Phase II Advanced Anal Cancer Trial Comparing Cisplatin Plus 5 FU vs Carboplatin Plus Weekly Paclitaxel in Patients With Inoperable Locally Recurrent or Metastatic Disease
Secondary ID [1] 0 0
2013-001949-13
Secondary ID [2] 0 0
CCR 3847 InterAACT
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 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Bowel - Anal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cisplatin
Treatment: Drugs - 5-Fluorouracil (5-FU)
Treatment: Drugs - Carboplatin
Treatment: Drugs - Paclitaxel

Active Comparator: Arm A - Cisplatin and 5-Fluorouracil

Experimental: Arm B - Carboplatin plus Paclitaxel


Treatment: Drugs: Cisplatin
Cisplatin 60 mg/m2 as a 1 hour i.v. infusion once every 3 weeks.

Treatment: Drugs: 5-Fluorouracil (5-FU)
5-FU 1000 mg/m2/24h as a 96-hour continuous infusion over days 1 to 4 every 3 weeks.

Treatment: Drugs: Carboplatin
Carboplatin 1-hour i.v. infusion to an area under the curve (AUC) of 5 once every 4 weeks.

Treatment: Drugs: Paclitaxel
Paclitaxel 80 mg/m2 as a 1-hour i.v. infusion on day 1,8 and 15 of each (4-weekly) cycle.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Best overall response rate by 24 weeks post treatment - 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 intention to treat population. Sensitivity analyse will also be performed.
Timepoint [1] 0 0
24 weeks
Secondary outcome [1] 0 0
Feasibility of conducting a multicentre, international study on squamous cell carcinoma of the anus and recruiting within a reasonable time frame. - 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).
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Toxicity - Toxicity will be graded according to the NCI CTCAE Version 4.0
Timepoint [2] 0 0
Toxicity will be analysed once all patients have been followed up for at least 4 weeks post treatment.
Secondary outcome [3] 0 0
Progression-free survival - 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.
Timepoint [3] 0 0
PFS will be analysed once all patients have been followed up for at least 12 months post treatment.
Secondary outcome [4] 0 0
Overall survival - 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.
Timepoint [4] 0 0
Overall survival will be analysed once all patients have been followed up for at least 12 months post treatment.
Secondary outcome [5] 0 0
Disease control rate - 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.
Timepoint [5] 0 0
12 and 24 weeks post treatment start
Secondary outcome [6] 0 0
Best overall response rate of non-irradiated lesions - 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.
Timepoint [6] 0 0
24 weeks post treatment start
Secondary outcome [7] 0 0
Anti-tumour activity and magnitude of tumour response - Anti-tumour activity and magnitude of response will be captured by waterfall plot analyses and indicate the percentage change in tumour size from baseline to the time of best response.
Timepoint [7] 0 0
24 weeks
Secondary outcome [8] 0 0
Quality of Life - 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.
Timepoint [8] 0 0
3 years
Secondary outcome [9] 0 0
Identification of potential tumour biomarker - Archived tumour tissue (if available) and blood sample will be taken at baseline with a repeat blood sample taken upon progression. Patient can enrol in an optional biomarker study where an additional tumour biopsy would be requested when they progress. The aim of this exploratory analysis is to evaluate the expression of tumour biomarkers in the study population and investigate the association of these with treatment outcome.
Timepoint [9] 0 0
3 years

Eligibility
Key inclusion criteria
Inclusion Criteria

1. Histologically or cytologically verified, uni-dimensionally measurable, inoperable,
locally recurrent or metastatic squamous cell carcinoma of the anus.

2. Age =18 years.

3. ECOG Performance status =2.

4. Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST)
criteria version 1.1.

5. Previous definitive chemoradiotherapy is permitted for early stage squamous cell
carcinoma of the anus.

6. HIV+ patients will be considered eligible with a CD4 count of =200.

7. Adequate cardiac and respiratory function; absolute neutrophil count (ANC)
=1.5x10^9/l; white blood cell (WBC) count =3x10^9/l; platelets >100x10^9/l;
haemoglobin (Hb) =9g/dl; creatinine clearance >50ml/minute; serum bilirubin =1.5x
upper limit of normal (ULN); alanine transaminase (ALT)/aspartate transaminase (AST)
=2.5x ULN; alkaline phosphatase (ALP) =3x ULN.

8. Fertile men and women must agree to take adequate contraceptive precautions during,
and for at least six months after therapy.

9. Life expectancy of at least 3 months.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. Tumours of adenocarcinoma, melanoma, small cell and basal cell histology are excluded.

2. Previous chemotherapy, radiotherapy or other investigational drug for surgically
unresectable locally recurrent or advanced squamous cell carcinoma of the anus

3. Current or recent (within 30 days of first study dosing) treatment with another
investigational drug or participation in another investigational study.

4. Documented or symptomatic brain metastases and/or central nervous system metastases or
leptomeningeal disease.

5. Surgery or palliative radiotherapy within 28 days of randomisation.

6. 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.

7. History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or
evidence of interstitial lung disease on baseline chest CT scan.

8. Lack of physical integrity of the gastro-intestinal tract, malabsorption syndrome
(naso-gastric or jejunostomy feeding tube is permitted).

9. Acute hepatitis C and/or chronic active hepatitis B infection.

10. Serious active infection requiring i.v. antibiotics at enrolment.

11. 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.

12. Other clinically significant disease or co-morbidity that may adversely affect the
safe delivery of treatment within this trial.

13. Known hypersensitivity to any of the study drugs or excipients.

14. Known peripheral neuropathy = grade 1 (absence of deep tendon reflexes as the sole
neurological abnormality does not render the patient ineligible).

15. Pre-existing hearing impairment.

16. Patients planning for a live vaccine.

17. 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
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
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] 0 0
Margot Gorzeman - Sydney
Recruitment postcode(s) [1] 0 0
NSW 1450 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United Kingdom
State/province [2] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Other
Name
Royal Marsden NHS Foundation Trust
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Cancer Research UK
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Australasian Gastro-Intestinal Trials Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
ECOG-ACRIN Cancer Research Group
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
International Rare Cancers Initiative (IRCI ) This study is indorsed by IRCI
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Anal cancer is a relatively uncommon disease and there is currently no standard chemotherapy
treatment for patients with inoperable locally recurrent or metastatic disease. The aim of
this phase II study is compare two well known and largely used chemotherapy regimens -
Cisplatin plus 5-fluorouracil vs Carboplatin plus Paclitaxel. The result of this study will
set a standard of care for this disease and provide useful information for future Phase III
trials.
Trial website
https://clinicaltrials.gov/show/NCT02051868
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sheela Rao, MD, FRCP
Address 0 0
Royal Marsden NHS Foundation Trust
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sheela Rao, MD, FRCP
Address 0 0
Country 0 0
Phone 0 0
+44 (0) 0208 642 6011
Fax 0 0
Email 0 0
sheela.rao@rmh.nhs.uk
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02051868