Edotecarin and Cisplatin in Treating Patients With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as edotecarin and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Combining edotecarin with cisplatin may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining edotecarin with cisplatin in treating patients who have advanced or metastatic solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose and recommended phase II dose of edotecarin when administered with cisplatin (administered in 2 different schedules) in patients with advanced or metastatic solid tumors. Secondary Determine the safety profile of this regimen in these patients. Determine the plasma pharmacokinetics of this regimen in these patients. Determine the antitumor activity of this regimen in these patients. OUTLINE: This is an open-label, multicenter, dose-escalation study of edotecarin. Patients are assigned to 1 of 2 schedules. Schedule A: Patients receive cisplatin IV over 30 minutes and edotecarin IV over 1 hour on days 1 and 8. Schedule B: Patients receive cisplatin IV over 2 hours and edotecarin IV over 1 hour on day 1. In both schedules, courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients in each schedule receive escalating doses of edotecarin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients with metastatic esophageal or gastric cancer receive treatment as above at the MTD. Patients are followed every 2 months for 1 year or until disease progression. PROJECTED ACCRUAL: A maximum of 80 patients (40 per schedule) will be accrued for this study.

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

Conditions
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Esophageal Cancer, Gastric Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: cisplatin
* Drug: edotecarin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: edotecarin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific, stage IV esophageal cancer, stage IV gastric cancer