Bryostatin 1 Plus Gemcitabine in Treating Patients With Advanced Cancer

Barbara Ann Karmanos Cancer Institute

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: gemcitabine hydrochloride; Drug: bryostatin 1

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00004144

CDR0000067375

WSU-Z-2021

P30CA022453 (U.S. NIH Grant/Contract)

NCI-T99-0014

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

bryostatin 1 & gemcitabine hydrochloride

Experimental group

Treatment:

Drug: bryostatin 1

Drug: gemcitabine hydrochloride