Clinical trial NCT00004144: Bryostatin 1 Plus Gemcitabine in Treating Patients With Advanced Cancer
Official title: Phase I Study of Bryostatin 1 and Gemcitabine (Gemzar)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Philip A. Philip, MD, PhD, FRCP
role: STUDY_CHAIR
References:
citation: El-Rayes BF, Gadgeel S, Shields AF, Manza S, Lorusso P, Philip PA. Phase I study of bryostatin 1 and gemcitabine. Clin Cancer Res. 2006 Dec 1;12(23):7059-62. doi: 10.1158/1078-0432.CCR-06-1419.