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An Open-Label, Non-Randomized Phase I Study of the Protein Kinase C Inhibitor Bryostatin-1 Administered in Combination With Paclitaxel in Patients With Advanced Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

An Open-Label, Non-Randomized Phase I Study of the Protein Kinase C Inhibitor Bryostatin-1 Administered in Combination With Paclitaxel in Patients With Advanced Solid Tumors


OBJECTIVES: I. Determine the maximum tolerated dose of intravenous bryostatin 1 when
administered in combination with a fixed dose of paclitaxel and cisplatin in patients with
advanced solid tumors. II. Investigate the clinical pharmacokinetics of intravenous
paclitaxel when administered in combination with bryostatin 1 in these patients. III. Obtain
preliminary data on the therapeutic activity of this therapy in these patients and evaluate
surrogate markers of activity.

OUTLINE: This is an open label, dose escalation study. Patients receive paclitaxel IV over 1
hour on day 1. On day 2, patients receive bryostatin 1 IV over 1 hour immediately followed
by cisplatin IV on day 2. Treatment is repeated weekly for 3 consecutive weeks followed by
one week of rest for at least 2 courses. Treatment continues in the absence of disease
progression or unacceptable toxicity. Cohorts of 3-6 patients are entered at escalating dose
levels of bryostatin 1 and paclitaxel. If 2 of 6 patients experience dose limiting toxicity
(DLT) at any given dose level, then the maximum tolerated dose (MTD) is declared to be the
preceding dose level. Once the MTD of paclitaxel and bryostatin 1 has been established,
escalations of weekly cisplatin will be added. Additional patient cohorts receive two
escalating doses of paclitaxel and cisplatin with the fixed bryostatin 1 dose level, in the
absence of DLT. Patients at a lower bryostatin 1 dose may be escalated to a higher
bryostatin 1 dose, only if that higher dose has been proven to be safe in another cohort of
patients.

PROJECTED ACCRUAL: An anticipated 3 to 60 patients will be accrued for this study within
1-14 months.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically confirmed advanced solid tumor Must be refractory
to standard therapy or no standard therapy exists No CNS metastases or CNS primary
malignancy

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life
expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Absolute neutrophil count
at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than
1.5 mg/dL SGOT and SGPT no greater than 2.5 times upper limit of normal Renal: Creatinine
no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular:
No history of cardiac arrhythmias No congestive heart failure No myocardial infarction in
the last 6 months Neurologic: No grade 3 or greater neurotoxicity Other: HIV negative No
serious or uncontrolled infection Not pregnant Adequate contraception required of all
fertile patients during study and until 2 months after study

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy and
recovered Chemotherapy: At least 6 weeks since prior nitrosoureas or mitomycin At least 4
weeks since other prior chemotherapy Must have recovered from prior chemotherapy Endocrine
therapy: Must have recovered from prior endocrine therapy Radiotherapy: At least 4 weeks
since prior radiotherapy and recovered Surgery: Not specified

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Gary K. Schwartz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

97-139

NCT ID:

NCT00003242

Start Date:

February 1998

Completion Date:

October 2001

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021