trial of pi-88 with docetaxel in advanced non-small-cell lung cancer (nsclc)

Conditions: Carcinoma, Non-Small-Cell Lung

Summary: 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.

Eligibility criteria:
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

Keywords: second-line combination chemotherapy anti-angiogenic