Bryostatin 1 Plus Gemcitabine in Treating Patients With Advanced Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of bryostatin 1 plus gemcitabine in treating patients who have advanced cancer that has not responded to previous treatment.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of gemcitabine when given concurrently with bryostatin 1 to patients with advanced refractory cancer. Access the pattern of toxicity of this drug regimen in this patient population. Determine the objective response rate, duration of response, and overall survival in patients treated with this drug regimen. Determine the influence of bryostatin 1 on the pharmacokinetics of gemcitabine. OUTLINE: This is a dose escalation study. Patients receive gemcitabine IV over 30 minutes, immediately followed by bryostatin 1 IV over 24 hours, weekly for 3 weeks (days 1, 8, and 15). Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of gemcitabine and bryostatin 1 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 toxic effects. PROJECTED ACCRUAL: Approximately 2-3 patients per month will be accrued for this study.

Official Title
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Phase I Study of Bryostatin 1 and Gemcitabine (Gemzar)

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: bryostatin 1
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically proven advanced cancer (except hematological cancers) for which there is no standard therapy or have failed standard therapies Measurable or evaluable disease Clinically controlled brain metastases allowed PATIENT CHARACTERISTICS: Age: 18 and over Performance status: SWOG 0-2 Life expectancy: At least 3 months Hematopoietic: Hemoglobin at least 8.0 g/dL Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) (elevated bilirubin due to Gilbert's syndrome allowed if direct bilirubin normal) AST less than 2.5 times ULN Renal: Creatinine normal Cardiovascular: No active cardiac disease Other: Not pregnant or nursing Fertile patients must use effective contraception No concurrent bacterial infection requiring antibiotics No serious concurrent medical condition PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: At least 3 weeks since systemic cytotoxic chemotherapy (including gemcitabine) and recovered No other concurrent chemotherapy Endocrine therapy: Prior hormonal therapy allowed No concurrent hormonal therapy (excluding contraceptives, appetite stimulants, or replacement steroids) Radiotherapy: At least 3 weeks since radiotherapy to large areas of active bone marrow and recovered No concurrent radiotherapy Surgery: Recovered from prior major surgery Other: No concurrent antiviral nucleosides At least 1 month since prior investigational agents No other concurrent experimental medications

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: bryostatin 1 & gemcitabine hydrochloride<br> | Drug: bryostatin 1<br> <br> Drug: gemcitabine hydrochloride<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