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An Open-Labeled, Non-Randomized Phase I Study Of Flavopiridol Administered With Irinotecan (CPT-11) 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-Labeled, Non-Randomized Phase I Study Of Flavopiridol Administered With Irinotecan (CPT-11) In Patients With Advanced Solid Tumors


OBJECTIVES:

- Determine the maximum tolerated dose of flavopiridol when combined with irinotecan in
patients with advanced solid tumors.

- Determine the clinical pharmacokinetics of this regimen, as well as the plasma levels
of the active metabolite SN-38 and metabolic product SN-38 glucuronide in these
patients.

- Determine, in a preliminary manner, the therapeutic activity of this regimen in these
patients.

- Determine the role of p21 relative to treatment response and apoptosis in these
patients treated with this regimen.

OUTLINE: This is a dose-escalation, open-label, non-randomized study of flavopiridol.

Patients receive irinotecan IV over 30 minutes followed 7 hours later by flavopiridol IV
over 1 hour on days 1, 8, 15, and 22. Treatment continues every 6 weeks for a minimum of 2
courses in the absence of disease progression or unacceptable toxicity. During the first
week of the second course, patients receive flavopiridol alone on day 1 and irinotecan alone
on day 2.

Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more
of 6 patients in the initial cohort experience dose limiting toxicity during the first
course of treatment. An additional 10 patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 44-50 patients will be accrued for this study within 1 year.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically proven locally advanced or metastatic solid tumor that is refractory
to standard therapy or for which no standard therapy exists

- Eligible for treatment at the maximum tolerated dose only if disease accessible for
tissue biopsy by Tru-Cut, CT guidance, or endoscopy

- Pleural effusions or abdominal ascites do not constitute adequate tissue for
biopsy

- No known CNS metastasis or primary CNS tumor

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 60-100%

Life expectancy:

- Not specified

Hematopoietic:

- WBC at least 3,500/mm^3

- Total neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

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

Cardiovascular:

- No cardiac arrhythmias, congestive heart failure, or myocardial infarction within the
past 6 months

Other:

- Not pregnant or nursing (during and for at least 2 months after study)

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 2 months
after study

- No concurrent serious or uncontrolled infection

- HIV negative

- No other medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 4 weeks since prior immunotherapy and recovered

Chemotherapy:

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and
recovered

- Prior irinotecan allowed

Endocrine therapy:

- Not specified

Radiotherapy:

- At least 4 weeks since prior radiotherapy and recovered

Surgery:

- See Disease Characteristics

Other:

- Recovered from prior therapy

- No other concurrent investigational medication

- No concurrent vitamins (except a single multivitamin tablet), antioxidants, or herbal
preparations or supplements

- No concurrent subcutaneous heparin or heparinoids

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Masking: Open Label, 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:

CDR0000068316

NCT ID:

NCT00006485

Start Date:

September 2000

Completion Date:

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