A Phase I Dose Escalation Study of Edotecarin (PHA-782615) and Cisplatin in Adult Patients With Advanced/Metastatic Solid Tumors

Date de début de l'étude : 1 août 2003

DISEASE CHARACTERISTICS: * Diagnosis of one of the following: * Histologically or cytologically confirmed active solid tumor malignancy * Histologically confirmed esophageal or gastric cancer\* meeting all the following criteria: * Previously untreated disease * Metastatic disease * Measurable disease * At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR 10 mm by spiral CT scan NOTE: \*Patients with esophageal or gastric cancer are enrolled after the maximum tolerated dose has been determined * No known brain or leptomeningeal disease PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-1 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin at least 9.0 g/dL Hepatic * Bilirubin no greater than 1.5 times upper limit of normal (ULN) (regardless of liver involvement by tumor) * SGOT no greater than 3 times ULN (5 times ULN if there is liver involvement by tumor) * Albumin at least 3.0 g/dL Renal * Creatinine no greater than 1.5 mg/dL Cardiovascular * None of the following within the past 12 months: * Myocardial infarction * Severe/unstable angina * Symptomatic congestive heart failure * Cerebrovascular accident * Transient ischemic attack * Deep vein thrombosis * Other significant thromboembolic event * No ongoing grade 2 or greater cardiac dysrhythmia * No atrial fibrillation Pulmonary * No pulmonary embolism within the past 12 months Gastrointestinal * No active inflammatory bowel disease * No partial or complete bowel obstruction * No chronic diarrhea Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative * No grade 2 or greater acute toxic effects * No active infection * No other concurrent acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No prior treatment with any of the following systemic therapies for metastatic cancer\*: * Antibody therapy * Immunotherapy * Gene therapy * Vaccine therapy * Cytokine therapy * Inhibitors of vascular endothelial growth factor/Flk-1 pathway * No concurrent sargramostim (GM-CSF) * No concurrent antibody therapy or immunotherapy NOTE: \*Patients with esophageal or gastric cancer only Chemotherapy * No more than 1 prior chemotherapy regimen for metastatic disease\* * No prior high-dose chemotherapy requiring hematopoietic stem cell rescue * No other concurrent chemotherapy NOTE: \*No prior chemotherapy for metastatic disease for patients with esophageal or gastric cancer Endocrine therapy * No concurrent hormonal treatment Radiotherapy * No prior radiotherapy to more than 25% of bone marrow reserve * No prior radiotherapy to the sole measurable lesion\* * No concurrent radiotherapy NOTE: \*Patients with esophageal or gastric cancer only Surgery * More than 12 months since prior coronary/peripheral artery bypass graft surgery Other * Recovered from prior therapy * More than 6 months since last dose of prior adjuvant therapy\* * No prior treatment with any of the following systemic therapies for metastatic cancer\*: * Cyclooxygenase-2 inhibitors * Matrix metalloprotease inhibitors * Epidermal growth factor receptor inhibitors * Other experimental agents * No other concurrent anticancer therapy * No concurrent enrollment in another clinical trial * No other concurrent experimental drugs NOTE: \*Patients with esophageal or gastric cancer only