UCN-01 and Irinotecan in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: UCN-01 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining UCN-01 with chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining UCN-01 with irinotecan in treating patients who have advanced solid tumors.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose and recommended phase II dose of UCN-01 and irinotecan in patients with advanced solid tumors, primarily lung, ovarian, and gastrointestinal tumors. Determine the acute and chronic toxicity profile of this regimen in these patients. Determine the pharmacokinetics of this regimen in these patients. Determine, preliminarily, the anti-tumor effect of this regimen in these patients. OUTLINE: This is a dose-escalation study. Patients receive UCN-01 IV over 3 hours on day 1 and irinotecan IV over 90 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of UCN-01 and irinotecan 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. At least 6 patients are treated at the recommended phase II dose. Patients are followed at 1 month. PROJECTED ACCRUAL: Approximately 20-30 patients will be accrued for this study within 7-15 months.

Official Title
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The Pharmacokinetic and Safety Profile of UCN-01 in Combination With Irinotecan in Solid Tumors (Primarily Lung, Ovarian and GI Cancers)

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: 7-hydroxystaurosporine
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative therapy does not exist or is no longer effective Gastrointestinal, lung, and ovarian malignancies are given priority No brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy More than 3 months Hematopoietic WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin normal AST/ALT no greater than 2.5 times upper limit of normal (ULN) Renal Creatinine normal OR Creatinine clearance at least 60 mL/min Cardiovascular No symptomatic coronary artery disease No symptomatic cardiac dysfunction No symptoms suggestive of coronary artery disease LVEF at least 50% Pulmonary No symptomatic pulmonary dysfunction FEV_1 greater than 75% of predicted DLCO greater than 75% of predicted Other Amylase no greater than 2 times ULN No other concurrent uncontrolled illness No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No diabetes mellitus or random glucose more than 200 mg/dL No prior allergic reaction attributed to compounds of similar biological or chemical composition to UCN-01 or irinotecan (including rash and systemic allergic reaction causing hypotension and respiratory distress) No chronic diarrhea (more than 5 stools/day) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for 14 days before, during, and for at least 30 days after study participation PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Prior UCN-01 and irinotecan allowed Endocrine therapy Not specified Radiotherapy At least 4 weeks since prior radiotherapy and recovered No prior mediastinal radiation Surgery Not specified Other At least 14 days since prior warfarin No concurrent warfarin unless required for maintaining patency of existing, permanent IV catheters No concurrent commercial or other investigational anticancer agents or therapies No concurrent combination antiretroviral therapy for HIV-positive patients

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 7-hydroxystaurosporine|nan|
|Drug: irinotecan hydrochloride|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