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Phase I Study of Combination Therapy With Oral 9-Nitrocamptothecin and Oral Etoposide


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

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Trial Information

Phase I Study of Combination Therapy With Oral 9-Nitrocamptothecin and Oral Etoposide


OBJECTIVES: I. Determine the maximum tolerated dose, dose limiting toxicity, and safety of
nitrocamptothecin when administered with etoposide in patients with advanced solid tumors.
II. Determine the changes in expression and activity of topoisomerase I and II which occur
during administration of this treatment regimen in these patients. III. Determine the plasma
pharmacokinetics of this treatment regimen in these patients. IV. Compare the hematologic
and nonhematologic toxicities with this treatment regimen in patients 70 years of age and
older versus patients younger than 70 years of age.

OUTLINE: This is a dose escalation study of nitrocamptothecin. Patients receive oral
nitrocamptothecin on days 1-3 and oral etoposide on days 4-5 each week. Treatment continues
in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients
receive escalating doses of nitrocamptothecin 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 toxicities. Patients are followed every 4 weeks until toxicities
resolve.

PROJECTED ACCRUAL: Approximately 40-60 patients will be accrued for this study over 18 to 24
months.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically confirmed nonhematologic malignancy refractory to
available therapies or for which no curative therapy exists Measurable or evaluable
disease No active brain metastases, including evidence of cerebral edema by CT scan or
MRI, progression from a prior imaging study, or any requirement for steroids or clinical
symptoms of/from brain metastases

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At
least 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count
at least 100,000/mm3 Hepatic: Bilirubin less than 1.5 mg/dL ALT and AST less than 2 times
upper limit of normal (ULN) (unless clearly related to hepatic metastases) Renal:
Creatinine less than 1.5 times ULN Other: No other serious uncontrolled medical disorder
or active infection that would preclude study No dementia or altered mental status that
would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must
use effective contraception during and for 10 weeks after study

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy No
concurrent colony stimulating factors (e.g., filgrastim (G-CSF) or sargramostim (GM-CSF))
Chemotherapy: No prior topoisomerase I inhibitors (e.g., nitrocamptothecin,
aminocamptothecin, irinotecan, or topotecan) At least 4 weeks since prior chemotherapy (at
least 6 weeks since prior nitrosoureas, mitomycin, or carboplatin) No other concurrent
chemotherapy Endocrine therapy: See Disease Characteristics At least 4 weeks since prior
hormonal therapy No concurrent hormonal anticancer therapy Radiotherapy: At least 4 weeks
since prior radiotherapy involving at least 30% of the bone marrow No concurrent
radiotherapy Surgery: Not specified Other: No other concurrent experimental anticancer
medication

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

Determine the MTD of nitrocamptothecin. Cohorts of 3-6 patients receive escalating doses of nitrocamptothecin 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 toxicities.

Outcome Time Frame:

3 years

Safety Issue:

Yes

Principal Investigator

Daniel M. Sullivan, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

MCC-12177

NCT ID:

NCT00006047

Start Date:

June 2000

Completion Date:

February 2003

Related Keywords:

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

Name

Location

H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612