Endostatin in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of endostatin in treating patients who have advanced solid tumors. Endostatin may stop the growth of cancer by stopping blood flow to the tumor.

Detailed Description
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OBJECTIVES: I. Determine the optimal biologic dose of endostatin in patients with advanced solid tumors. II. Determine the safety and tolerability of this regimen in these patients. III. Determine the extent, frequency, and duration of tumor response in these patients on this regimen. IV. Determine the pharmacokinetic profile and interpatient pharmacologic variability of this regimen in these patients. V. Determine the recommended phase II dose and schedule of this regimen. OUTLINE: This is a dose escalation study. Patients undergo a biopsy during prestudy and after the second course of treatment. Patients receive endostatin IV daily for 4 weeks. Patients on dose level 1-6 receive endostatin over 20 minutes. Patients on dose level 7 receive endostatin over 40 minutes, with no treatment on day 2 of the first course only. Treatment continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of endostatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are followed for 1 month.

Official Title
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A Phase I Surrogate Endpoint Trial of Human Recombinant Endostatin in Patients With Advanced Solid Tumors Amenable to Biopsy

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: recombinant human endostatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven advanced solid tumor for which no standard curative therapy exists Must be amenable to biopsy At least 1 site of measurable disease outside of irradiated field No brain metastases by CT or MRI scan PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 WBC greater than 3,000/mm3 Absolute neutrophil count greater than 1,500/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 10 g/dL Bilirubin less than 1.5 times upper limit of normal (ULN) ALT and AST less than 2.0 times ULN PT/PTT less than 1.5 times ULN Creatinine less than 1.5 mg/dL OR creatinine clearance greater than 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No concurrent uncontrolled medical or psychiatric disorder No history of bleeding diathesis PRIOR CONCURRENT THERAPY: No concurrent over the counter biologic agents (e.g., shark cartilage) At least 3 weeks since prior chemotherapy (6 weeks since nitrosoureas or mitomycin) No more than 3 prior chemotherapy regimens for metastatic or recurrent disease (ECOG 1) Prior adjuvant chemotherapy for nonmetastatic disease allowed Concurrent stable dose of hormone replacement therapy allowed At least 3 weeks since prior radiotherapy No concurrent radiotherapy At least 24 hours since minor surgery (e.g., central venous placement) At least 4 weeks since major surgery (e.g., laparotomy, thoracotomy, or craniotomy) At least 30 days since other prior investigational agents No concurrent herbal remedies No concurrent usage of products containing heparin No other concurrent anticancer therapy Concurrent multivitamins allowed

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients undergo a biopsy during prestudy and after the second course of treatment. Patients receive endostatin IV daily for 4 weeks. Patients on dose level 1-6 receive endostatin over 20 minutes. Patients on dose level 7 receive endostatin over 40 minutes, with no treatment on day 2 of the first course only. Treatment continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of endostatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. | Biological: recombinant human endostatin<br> <br> |

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