An International Multicentre Open Label Randomised Phase II Advanced Anal Cancer Trial Comparing Cisplatin plus 5-fluorouracil versus Carboplatin plus Weekly Paclitaxel in Patients with Inoperable Locally Recurrent or Metastatic Disease

Exclusion Criteria23

• Tumours of adenocarcinoma, melanoma, small cell and basal cell histology are excluded.
• Newly diagnosed locally advanced tumour which requires upfront systemic chemotherapy but is still amenable to curative treatment (i.e. chemotherapy followed by definitive chemoradiotherapy)
• Locally recurrent tumour which is amenable to curative resection (as deemed by a local surgeon or Multidisciplinary Team).
• Tumour relapse/progression within 6 months of completion of a cisplatin-based chemoradiotherapy regimen for the treatment of early stage tumours.
• Previous administration of greater than 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease.
• Tumour progression during or immediately after completion of less than or equal to 2 cycles of systemic chemotherapy as induction treatment before definitive chemoradiotherapy for early stage disease.
• Previous use of systemic chemotherapy or other investigational drugs for the treatment of inoperable locally recurrent or metastatic tumours (previous use of radiotherapy in this setting is not an exclusion criterion if: 1) non-irradiated target tumour lesions are present at randomisation for the purpose of tumour response assessment or 2) in the absence of non-irradiated target tumour lesions, progression of the irradiated tumour lesions according to the RECIST criteria version 1.1 is documented).
• 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.
• Major surgery performed less than 28 days from treatment start.
• Palliative radiotherapy completed less than or equal to 7 days from treatment start.
• 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.
• HIV positive patients who are not on HAART or have a CD4 count of less than 200/microlitre in the presence of detectable plasma viral load according to the local assay.
• Known history of active hepatitis B or hepatitis C 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 greater than grade 1 (absence of deep tendon reflexes as thesole neurological abnormality does not render the patient ineligible).
• Pre-existing hearing impairment.
• Patients planning for a live vaccine.
• Pregnant or lactating females.