Clinical trial NCT02051868: International Multicentre Study in Advanced Anal Cancer Comparing Cisplatin Plus 5 FU vs Carboplatin Plus Weekly Paclitaxel
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
Overall status: UNKNOWN
Phase: PHASE2
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
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: Australasian Gastro-Intestinal Trials Group
name: ECOG-ACRIN Cancer Research Group
name: European Organisation for Research and Treatment of Cancer - EORTC
name: International Rare Cancers Initiative (IRCI ) This study is indorsed by IRCI
First posted: 2014-01-31
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Best overall response rate by 24 weeks post treatment
timeFrame: 24 weeks
Secondary outcomes:
measure: Feasibility of conducting a multicentre, international study on squamous cell carcinoma of the anus and recruiting within a reasonable time frame.
timeFrame: 3 years
measure: Toxicity
timeFrame: Toxicity will be analysed once all patients have been followed up for at least 4 weeks post treatment.
measure: Progression-free survival
timeFrame: PFS will be analysed once all patients have been followed up for at least 12 months post treatment.
measure: Overall survival
timeFrame: Overall survival will be analysed once all patients have been followed up for at least 12 months post treatment.
measure: Disease control rate
timeFrame: 12 and 24 weeks post treatment start
measure: Best overall response rate of non-irradiated lesions
timeFrame: 24 weeks post treatment start
measure: Anti-tumour activity and magnitude of tumour response
timeFrame: 24 weeks
measure: Quality of Life
timeFrame: 3 years
measure: Identification of potential tumour biomarker
timeFrame: 3 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Laura Gagnon
state: Massachusetts
city: Sydney
country: Australia
facility: Margot Gorzeman
state: New South Wales
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust, London & Sutton
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Sheela Rao, MD, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
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.