PI-88 is a new experimental drug that inhibits tumour growth by reducing the formation of new blood vessels into tumours. Docetaxel is a standard second-line treatment offered to patients with non-small-cell lung cancer who haven't responded to first-line therapies (platinum-based drugs or radiotherapy). Of this group of patients, only 20% remain progression-free 6 months after starting docetaxel treatment. The PR88202 study has been designed to compare two different cancer treatments (docetaxel only, and docetaxel plus PI-88) and to work out which is more effective against the cancer. It is hoped that the combination of PI-88 with docetaxel will allow patients to extend the time it takes for their disease to progress, and also to improve their quality of life.

PR88202 is an open-label randomized study. In the initial phase of the study, patients will be randomized to receive weekly docetaxel alone, or PI-88 in combination with weekly docetaxel. Both groups will receive docetaxel (30 mg/m2), administered by intravenous infusion on days 1, 8 and 15 of a 28-day cycle. The second group only will receive PI-88 (250 mg/day) in addition to docetaxel; PI-88 will be administered by subcutaneous injection on days 1-4, 8-11 and 15-18 of each cycle. The primary efficacy endpoint is the non-progression rate at 6 months. In the extension phase of the study, patients in the combination arm who have stable disease or an objective response after up to six treatment cycles will remain on PI-88 alone as maintenance therapy. Patients who initially receive docetaxel alone and who have disease progression or unacceptable toxicity before the completion of six cycles will be eligible to receive PI-88 alone as third-line therapy.

Inclusion Criteria:

• histologically or cytologically confirmed stage IIIb or IV NSCLC that has progressed during or after first-line treatment
• measurable disease by spiral CT chest scan, as defined in RECIST criteria
• performance status 0-1 (ECOG)
• life expectancy at least 2 months
• adequate hemopoietic, renal and hepatic function

Exclusion Criteria:

• current symptomatic central nervous system (CNS) involvement
• prior or co-existent malignancies
• significant non-malignant disease
• acute or chronic gastrointestinal (GI) bleeding in last two years
• inflammatory bowel disease
• abnormal bleeding tendency
• patients at risk of bleeding due to open wounds or planned surgery
• clinically significant hemoptysis within the past 4 weeks
• bilirubin > upper limit of normal (ULN)
• ALT and AST > 2.5 times ULN, or > 1.5 times ULN if alkaline phosphatase > 2.5 times ULN
• alkaline phosphatase > 5 times ULN, unless patient has bone metastases
• myocardial infarction, stroke or congestive heart failure within last 3 months
• prior treatment with docetaxel
• concomitant treatment with aspirin (>100 mg/day), NSAIDs (except selective COX-2 inhibitors, warfarin (>1 mg/day), heparin, LMWH, anti-platelet drugs, CYP3A4 inhibitors
• women who are pregnant or breast-feeding
• women of child-bearing potential not using adequate contraception
• history of allergy and/or hypersensitivity to anti-coagulants or thrombolytic agents, especially heparin
• history of immune-mediated thrombocytopenia, thrombotic thrombocytopenic purpura or other platelet disease
• allergy to polysorbate 80 (component of Taxotere®)
• uncontrolled or serious infection in last 4 weeks