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

NCT02051868 | Unknown Phase 2 DMC

• 2 other identifiers: CCR 3847 InterAACT2013-001949-13
• Study Type: interventional
• Target: 80
• Locations: 3 countries
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (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.

  24 weeks

Secondary Outcomes (9)

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

  3 years

• Toxicity

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

• Progression-free survival

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

• Overall survival

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

• Disease control rate

  12 and 24 weeks post treatment start

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Cisplatin and 5-Fluorouracil

Drug: Cisplatin; Drug: 5-Fluorouracil (5-FU)

Arm B

EXPERIMENTAL

Carboplatin plus Paclitaxel

Drug: Carboplatin; Drug: Paclitaxel

Interventions

Cisplatin DRUG

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

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

Arm A

5-Fluorouracil (5-FU) DRUG

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

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

Arm A

Carboplatin DRUG

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

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

Arm B

Paclitaxel DRUG

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

Also known as: (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

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Cancer Research UK: collaborator
• Australasian Gastro-Intestinal Trials Group: collaborator
• ECOG-ACRIN Cancer Research Group: collaborator
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator
• International Rare Cancers Initiative (IRCI ) This study is indorsed by IRCI: collaborator

Study Sites (3)

Laura Gagnon

Boston, Massachusetts, MA 02215, United States

NOT YET RECRUITING

Margot Gorzeman

Sydney, New South Wales, NSW 1450, Australia

NOT YET RECRUITING

Royal Marsden NHS Foundation Trust, London & Sutton

Sutton, SM2 5PT, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 32530769 DERIVED

MeSH Terms

Conditions

Anus Neoplasms; Neoplasm Metastasis

Interventions

Cisplatin; Fluorouracil; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Sheela Rao, MD, FRCP

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sheela Rao, MD, FRCP

CONTACT

+44 (0) 0208 642 6011; sheela.rao@rmh.nhs.uk

Francesco Sclafani, MD

CONTACT

+44 (0)) 0208 642 6011; francesco.sclafani@rmh.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2014
• First Posted: January 31, 2014
• Study Start: December 1, 2013
• Primary Completion: August 1, 2017
• Study Completion: February 1, 2018
• Last Updated: November 4, 2015

Record last verified: 2015-11

Locations

AU (1); GB (1); US (1)