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Squamous Cell Carcinoma of the AnusPhase 2InterAACTNCT02051868

International Multicentre Study in Advanced Anal Cancer Comparing Cisplatin Plus 5 FU vs Carboplatin Plus Weekly Paclitaxel

A Phase 2 study testing Cisplatin, 5-Fluorouracil (5-FU) and Carboplatin in people with Squamous Cell Carcinoma of the Anus, run by Royal Marsden NHS Foundation Trust at 3 sites in 3 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Squamous Cell Carcinoma of the Anus
What is being tested?
Cisplatin, 5-Fluorouracil (5-FU) and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
3 sitesin 3 countries
Study dates
Dec 2013to Feb 2018
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically verified, uni-dimensionally measurable, inoperable, locally recurrent or metastatic squamous cell carcinoma of the anus.
  • Age ≥18 years.
  • ECOG Performance status ≤2.
  • Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1.
  • Previous definitive chemoradiotherapy is permitted for early stage squamous cell carcinoma of the anus.
  • HIV+ patients will be considered eligible with a CD4 count of ≥200.
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  • 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.
  • 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.

Who cannot join

  • Tumours of adenocarcinoma, melanoma, small cell and basal cell histology are excluded.
  • Previous chemotherapy, radiotherapy or other investigational drug for surgically unresectable locally recurrent or advanced squamous cell carcinoma of the anus
  • 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.
  • Surgery or palliative radiotherapy within 28 days of randomisation.
  • 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.
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  • History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan.
  • Lack of physical integrity of the gastro-intestinal tract, malabsorption syndrome (naso-gastric or jejunostomy feeding tube is permitted).
  • Acute hepatitis C and/or chronic active hepatitis B 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 ≥ grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible).
  • Pre-existing hearing impairment.
  • Patients planning for a live vaccine.
  • Pregnant or lactating females.

Trial locations and contacts

3 sites in 3 countries.

Sheela Rao, MD, FRCP contact

+44 (0) 0208 642 6011 ext. 1380

sheela.rao@rmh.nhs.uk

Francesco Sclafani, MD contact

+44 (0)) 0208 642 6011 ext. 1293

francesco.sclafani@rmh.nhs.uk

3 sites in 3 countries

United States1 site, 1 recruiting

  • Laura Gagnon

    Boston, Massachusetts, MA 02215

    Laura Gagnon, 617-632-3610, gagnon.laura@jimmy.harvard.edu

    Not yet recruiting

Other trials in United States

Australia1 site, 1 recruiting

  • Margot Gorzeman

    Sydney, New South Wales, NSW 1450

    Margot Gorzeman, +61 295625359, interAACT@ctc.usyd.edu.au

    Not yet recruiting

Other trials in Australia

United Kingdom1 site, 1 recruiting

  • Royal Marsden NHS Foundation Trust, London & Sutton

    Sutton, SM2 5PT

    Annette Bryant, BSc (Hons), +44 (0) 0208 661 3637 ext. 3637, annette.bryant@rmh.nhs.uk

    Sheela Rao, MD.FRCP

    Recruiting

Other trials in United Kingdom

About this study

Official 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

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.

Read the detailed description

Study design: This is an international, multicentre, open label, randomised phase II trial. Patients will be randomised to receive either cisplatin plus 5-FU or carboplatin plus weekly paclitaxel. Region (Europe, North America, South America \& Australia), (Eastern Cooperative Oncology Group- ECOG) ECOG performance status (PS) (0-1 vs. 2), HIV status (positive vs. negative) and extent of disease (locally recurrent vs. metastatic) will be used as stratification factors. Overall response rate is the primary endpoint.

Indication: First line treatment of patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anus.

Length of study: Recruitment should be completed within 3 years. The estimated recruitment rate is between 4-6 patients per month once it is established at multiple centres.

Primary Objective: To evaluate best overall response rate by 24 weeks post treatment in the cisplatin plus 5-fluorouracil arm versus the carboplatin plus weekly paclitaxel arm

Secondary Objectives: To evaluate: - Progression-free survival - Overall survival - Disease control rate (stable disease or better) at 12 and 24 weeks - Best overall response of metastatic lesions - Toxicity (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 4) - Quality of Life (using EORTC QLQ-C30 version 3 and EQ-5D-5L questionnaires).

To assess: The feasibility of conducting a multicentre international study on squamous cell carcinoma of the anus and recruit within a reasonable time frame.

Exploratory Objective: Explorative biomarker analysis including the collection of archived tumour tissue and blood sample at baseline and upon progression.

Being tested
Cisplatin, 5-Fluorouracil (5-FU), Carboplatin, Paclitaxel
Keywords
Squamous cell carcinoma of the anus, Anal cancer, Cancer of the anus, SCCA, Cisplatin-5FU, Carboplatin-Paclitaxel, inoperable, locally recurrent, metastatic
Medical subject headings
Anus Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CisplatinDrug

    Also called Systematic (IUPAC) name: (SP-4-2)-diamminedichloridoplatinum, CAS number 15663-27-1 Y, ATC code L01XA01

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

  • 5-Fluorouracil (5-FU)Drug

    Also called Systematic (IUPAC) name: 5-fluoro-1H,3H-pyrimidine-2,4-dione, CAS number 51-21-8 Y, ATC code L01BC02

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

  • CarboplatinDrug

    Also called Systematic (IUPAC) name: cis-diammine(cyclobutane-1,1-dicarboxylate-O,O')platinum(II), CAS number 41575-94-4 Y, ATC code L01XA02

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

  • PaclitaxelDrug

    Also called (2α,4α,5β,7β,10β,13α)-4,10-bis(acetyloxy)-13-{[(2R,3S)- 3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy}- 1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate, CAS number 33069-62-4 Y, ATC code L01CD01

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

Study groups in NCT02051868
Study groupRoleWhat they receive
Arm AActive comparatorCisplatin and 5-Fluorouracil
Receives: Drug: Cisplatin; Drug: 5-Fluorouracil (5-FU)
Arm BExperimentalCarboplatin plus Paclitaxel
Receives: Drug: Carboplatin; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 24 weeks

Secondary outcomes (9)

  1. 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).

    Measured: 3 years

  2. Toxicity

    Toxicity will be graded according to the NCI CTCAE Version 4.0

    Measured: Toxicity will be analysed once all patients have been followed up for at least 4 weeks post treatment.

  3. 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.

    Measured: PFS will be analysed once all patients have been followed up for at least 12 months post treatment.

  4. 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.

    Measured: Overall survival will be analysed once all patients have been followed up for at least 12 months post treatment.

  5. 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.

    Measured: 12 and 24 weeks post treatment start

  6. 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.

    Measured: 24 weeks post treatment start

  7. 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.

    Measured: 24 weeks

  8. 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.

    Measured: 3 years

  9. 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.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2014 (estimated)
  2. Study startDec 2013
  3. Primary completionAug 2017 (estimated)
  4. Study completionFeb 2018 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02051868
Sponsor's protocol ID
CCR 3847 InterAACT
Other IDs
2013-001949-13
Acronym
InterAACT
Status last verified
Nov 2015
First submitted
13 Jan 2014
Last updated
4 Nov 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Rao S, Sclafani F, Eng C, Adams RA, Guren MG, Sebag-Montefiore D, Benson A, Bryant A, Peckitt C, Segelov E, Roy A, Seymour MT, Welch J, Saunders MP, Muirhead R, O'Dwyer P, Bridgewater J, Bhide S, Glynne-Jones R, Arnold D, Cunningham D. International Rare Cancers Initiative Multicenter Randomized Phase II Trial of Cisplatin and Fluorouracil Versus Carboplatin and Paclitaxel in Advanced Anal Cancer: InterAAct. J Clin Oncol. 2020 Aug 1;38(22):2510-2518. doi: 10.1200/JCO.19.03266. Epub 2020 Jun 12.

    PubMed 32530769

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cisplatin, 5-Fluorouracil (5-FU) and Carboplatin in people with Squamous Cell Carcinoma of the Anus, run by Royal Marsden NHS Foundation Trust at 3 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Australia, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Sheela Rao, MD, FRCP (+44 (0) 0208 642 6011 ext. 1380, sheela.rao@rmh.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best overall response rate by 24 weeks post treatment (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02051868, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2015.

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