Cisplatin and Fluorouracil Compared With Carboplatin and Paclitaxel in Treating Patients With Inoperable Locally Recurrent or Metastatic Anal Cancer

Inclusion Criteria:

• Inoperable, locally recurrent or metastatic disease (tumor resectability should beassessed by a local surgeon or multidisciplinary team)
• Histological or cytological confirmation of epidermoid anal carcinoma (includessquamous, basaloid and cloacogenic lesions) from the primary tumor or a newlydiagnosed recurrent/metastatic lesion
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)criteria version 1.1
• Previous definitive chemo-radiation is permitted for early stage tumors (cisplatin-based chemotherapy [chemo]-radiation is permitted but only if tumorprogression/relapse occurs after 6 months from treatment completion)
• Previous systemic chemotherapy is permitted if administered as induction treatment (=< 2 cycles) before definitive chemoradiotherapy for early stage disease and there is noevidence of tumor progression during or after treatment completion
• Human immunodeficiency virus positive (HIV+) patients will be considered eligible ifthey are on highly active anti-retroviral therapy (HAART) and have a cluster ofdifferentiation (CD)4 count of >= 200/ul (HIV+ patients who are on HAART and have aCD4 count < 200/ul are eligible if the plasma viral load is below the level ofdetection according to the local assay)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/l
• Platelets >= 100 x 10^9/l
• Hemoglobin (Hb) >= 9 g/dl for males and >= 8 g/dl for females
• Creatinine clearance >= 50 ml/minute
• Serum bilirubin =< 1.5 x upper limit of normal (ULN)
• Alanine transaminase (ALT) or aspartate transaminase (AST) =< 3 x ULN (if livermetastases are present, serum transaminases =< 5 x ULN are permitted)
• 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:

• Tumors of adenocarcinoma, melanoma, small cell and basal cell histology are excluded
• Locally recurrent tumor which is amenable to curative resection (as deemed by a localsurgeon or multidisciplinary team)
• Tumor relapse/progression within 6 months of completion of a cisplatin-basedchemoradiotherapy regimen for the treatment of early stage tumors
• Previous administration of > 2 cycles of systemic chemotherapy as induction treatmentbefore definitive chemoradiotherapy for early stage disease
• Tumor progression during or immediately after completion of =< 2 cycles of systemicchemotherapy as induction treatment before definitive chemoradiotherapy for earlystage disease
• Previous use of systemic chemotherapy or other investigational drugs for the treatmentof inoperable locally recurrent or metastatic tumors (previous use of radiotherapy inthis setting is not an exclusion criterion if: 1) non-irradiated target tumor lesionsare present at randomization for the purpose of tumor response assessment or 2) in theabsence of non-irradiated target tumor lesions, progression of the irradiated tumorlesions according to the RECIST criteria version 1.1 is documented)
• Current or recent (within 30 days of first study dosing) treatment with anotherinvestigational drug or participation in another investigational study
• Documented or symptomatic brain metastases and/or central nervous system metastases orleptomeningeal disease
• Major surgery performed < 28 days from treatment start
• Palliative radiotherapy completed =< 7 days from treatment start
• Clinically significant (i.e. active) cardiac disease (e.g. symptomatic coronary arterydisease, uncontrolled cardiac arrhythmia, or myocardial infarction within the last 6months); any history of clinically significant cardiac failure
• History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) orevidence of interstitial lung disease on baseline chest computed tomography (CT) scan
• HIV+ patients who are not on HAART or have a CD4 count of < 200/ul in the presence ofdetectable plasma viral load according to the local assay
• Known history of active hepatitis B or hepatitis C infection
• Serious active infection requiring intravenous (i.v.) antibiotics at enrollment
• Other malignancy within the last 5 years, except for adequately treated carcinoma insitu of the cervix or squamous carcinoma of the skin, or adequately controlled limitedbasal cell skin cancer
• Other clinically significant disease or co-morbidity that may adversely affect thesafe 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 soleneurological abnormality does not render the patient ineligible)
• Pre-existing hearing impairment
• Patients planning for a live vaccine
• Pregnant or lactating females