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

Primary Purpose

Squamous Cell Carcinoma of the Anus

Status

Unknown status

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Cisplatin

5-Fluorouracil (5-FU)

Carboplatin

Paclitaxel

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of the Anus focused on measuring Squamous cell carcinoma of the anus, Anal cancer, Cancer of the anus, SCCA, Cisplatin-5FU, Carboplatin-Paclitaxel, inoperable, locally recurrent, metastatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

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.
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.

Exclusion Criteria

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.
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.

Sites / Locations

Laura Gagnon
Margot Gorzeman
Royal Marsden NHS Foundation Trust, London & SuttonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A

Arm B

Arm Description

Cisplatin and 5-Fluorouracil

Carboplatin plus Paclitaxel

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

Toxicity

Toxicity will be graded according to the NCI CTCAE Version 4.0

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT02051868

First Posted

January 13, 2014

Last Updated

November 3, 2015

Sponsor

Royal Marsden NHS Foundation Trust

Collaborators

Cancer Research UK, Australasian Gastro-Intestinal Trials Group, ECOG-ACRIN Cancer Research Group, European Organisation for Research and Treatment of Cancer - EORTC, International Rare Cancers Initiative (IRCI ) This study is indorsed by IRCI

1. Study Identification

Unique Protocol Identification Number

NCT02051868

Brief Title

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

Acronym

InterAACT

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Unknown status

Study Start Date

December 2013 (undefined)

Primary Completion Date

August 2017 (Anticipated)

Study Completion Date

February 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Royal Marsden NHS Foundation Trust

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Squamous Cell Carcinoma of the Anus

Keywords

Squamous cell carcinoma of the anus, Anal cancer, Cancer of the anus, SCCA, Cisplatin-5FU, Carboplatin-Paclitaxel, inoperable, locally recurrent, metastatic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Active Comparator

Arm Description

Cisplatin and 5-Fluorouracil

Arm Title

Arm B

Arm Type

Experimental

Arm Description

Carboplatin plus Paclitaxel

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

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

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

5-Fluorouracil (5-FU)

Other Intervention Name(s)

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

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

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

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

(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

Intervention Description

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

Primary Outcome Measure Information:

Title

Best overall response rate by 24 weeks post treatment

Description

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Feasibility of conducting a multicentre, international study on squamous cell carcinoma of the anus and recruiting within a reasonable time frame.

Description

Time Frame

3 years

Title

Toxicity

Description

Toxicity will be graded according to the NCI CTCAE Version 4.0

Time Frame

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

Title

Progression-free survival

Description

Time Frame

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

Title

Overall survival

Description

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.

Time Frame

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

Title

Disease control rate

Description

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.

Time Frame

12 and 24 weeks post treatment start

Title

Best overall response rate of non-irradiated lesions

Description

Time Frame

24 weeks post treatment start

Title

Anti-tumour activity and magnitude of tumour response

Description

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.

Time Frame

24 weeks

Title

Quality of Life

Description

Time Frame

3 years

Title

Identification of potential tumour biomarker

Description

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria 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. 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. Exclusion Criteria 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. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sheela Rao, MD, FRCP

Phone

+44 (0) 0208 642 6011

Ext

1380

sheela.rao@rmh.nhs.uk

First Name & Middle Initial & Last Name or Official Title & Degree

Francesco Sclafani, MD

Phone

+44 (0)) 0208 642 6011

Ext

1293

francesco.sclafani@rmh.nhs.uk

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sheela Rao, MD, FRCP

Organizational Affiliation

Royal Marsden NHS Foundation Trust

Official's Role

Principal Investigator

Facility Information:

Facility Name

Laura Gagnon

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

MA 02215

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Laura Gagnon

Phone

617-632-3610

gagnon.laura@jimmy.harvard.edu

Facility Name

Margot Gorzeman

City

Sydney

State/Province

New South Wales

ZIP/Postal Code

NSW 1450

Country

Australia

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Margot Gorzeman

Phone

+61 295625359

interAACT@ctc.usyd.edu.au

Facility Name

Royal Marsden NHS Foundation Trust, London & Sutton

City

Sutton

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Annette Bryant, BSc (Hons)

Phone

+44 (0) 0208 661 3637

Ext

3637

annette.bryant@rmh.nhs.uk

First Name & Middle Initial & Last Name & Degree

Sheela Rao, MD.FRCP

12. IPD Sharing Statement

Citations:

PubMed Identifier

32530769

Citation

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.

Results Reference

derived

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

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