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

NCT ID: NCT02051868

Last Updated: 2015-11-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2018-02-28

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.

Conditions

Squamous Cell Carcinoma of the Anus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Cisplatin and 5-Fluorouracil

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

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

5-Fluorouracil (5-FU)

Intervention Type: DRUG

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

Arm B

Carboplatin plus Paclitaxel

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: DRUG

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

Interventions

Cisplatin

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

Intervention Type: DRUG

5-Fluorouracil (5-FU)

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

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Paclitaxel

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

Intervention Type: DRUG

Other Intervention Names

Systematic (IUPAC) name: (SP-4-2)-diamminedichloridoplatinum; CAS number 15663-27-1 Y; ATC code L01XA01; Systematic (IUPAC) name: 5-fluoro-1H,3H-pyrimidine-2,4-dione; CAS number 51-21-8 Y; ATC code L01BC02; Systematic (IUPAC) name: cis-diammine(cyclobutane-1,1-dicarboxylate-O,O')platinum(II); CAS number 41575-94-4 Y; ATC code L01XA02; (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

Eligibility 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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research UK

OTHER

Sponsor Role: collaborator

Australasian Gastro-Intestinal Trials Group

NETWORK

Sponsor Role: collaborator

ECOG-ACRIN Cancer Research Group

NETWORK

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

International Rare Cancers Initiative (IRCI ) This study is indorsed by IRCI

UNKNOWN

Sponsor Role: collaborator

Royal Marsden NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sheela Rao, MD, FRCP

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden NHS Foundation Trust

Locations

Laura Gagnon

Boston, Massachusetts, United States

Site Status: NOT_YET_RECRUITING

Margot Gorzeman

Sydney, New South Wales, Australia

Site Status: NOT_YET_RECRUITING

Royal Marsden NHS Foundation Trust, London & Sutton

Sutton, , United Kingdom

Site Status: RECRUITING

Countries

United States; Australia; United Kingdom

Central Contacts

Sheela Rao, MD, FRCP

Role: CONTACT

sheela.rao@rmh.nhs.uk

+44 (0) 0208 642 6011 ext. 1380

Francesco Sclafani, MD

Role: CONTACT

francesco.sclafani@rmh.nhs.uk

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

Facility Contacts

Laura Gagnon

Role: primary

gagnon.laura@jimmy.harvard.edu

617-632-3610

Margot Gorzeman

Role: primary

interAACT@ctc.usyd.edu.au

+61 295625359

Annette Bryant, BSc (Hons)

Role: primary

annette.bryant@rmh.nhs.uk

+44 (0) 0208 661 3637 ext. 3637

References

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.

Reference Type: DERIVED

PMID: 32530769 (View on PubMed)

Other Identifiers

2013-001949-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CCR 3847 InterAACT

Identifier Type: -

Identifier Source: org_study_id