Know Cancer

or
forgot password

An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors


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

Thank you

Trial Information

An Open-Labeled, Non-Randomized Phase I Study of Alvocidib (Flavopiridol) Administered With Irinotecan (CPT-11) and Fluorouracil/Leucovorin in Patients With Advanced Solid Tumors


PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of flavopiridol (alvocidib) when administered with
irinotecan hydrochloride, fluorouracil, and leucovorin calcium in patients with locally
advanced or metastatic solid tumors.

II. Determine the clinical pharmacokinetics of fluorouracil when administered in this
regimen in these patients.

III. Determine, preliminarily, the therapeutic activity of this regimen in these
patients.Correlate the role of p21 and Drg1 with apoptosis and treatment response in
patients receiving this regimen.

OUTLINE: This is a dose-escalation study of alvocidib and fluorouracil (5-FU).

Patients receive irinotecan hydrochloride IV over 90 minutes followed 5 hours later by
leucovorin calcium IV over 2 hours and alvocidib IV over 1 hour immediately followed by 5-FU
IV continuously over 48 hours beginning on day 1 of weeks 1, 3, and 5. Courses repeat every
6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6
patients receive escalating doses of alvocidib and 5-FU until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. Ten additional patients are treated at the MTD.

PROJECTED ACCRUAL: A total of 27-77 patients will be accrued for this study within 11-38
months.


Inclusion Criteria:



- Histologically or cytologically confirmed locally advanced or metastatic solid tumor

- Refractory to standard therapy or for which there is no standard therapy

- Preference given to colorectal cancer, upper gastrointestinal cancer, or
neuroendocrine tumors

- Evaluable disease

- No CNS metastases or primary CNS malignancy

- Performance status - Karnofsky 60-100%

- WBC at least 3,500/mm^3

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

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

- Bilirubin no greater than 1.5 mg/dL

- AST and ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if
liver metastases are present)

- Creatinine no greater than 1.5 mg/dL

- No history of cardiac arrhythmia

- No congestive heart failure

- No myocardial infarction within the past 6 months

- No prior grade 3 or 4 diarrhea secondary to irinotecan, despite optimal
antidiarrheal prophylaxis

- HIV negative

- No serious or uncontrolled infection

- No other medical condition or reason that would preclude study participation

- Not pregnant or nursing

- Negative pregnancy test

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

- At least 2 weeks since prior immunotherapy

- No more than 2 prior chemotherapy regimens unless there is no evidence of significant
myelotoxicity as determined by the primary investigator

- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)

- Prior irinotecan and fluorouracil allowed

- At least 2 weeks since prior radiotherapy

- Recovered from all prior therapy

- No other concurrent investigational medications

- No concurrent vitamins, antioxidants, or herbal preparations or supplements except a
single daily multivitamin

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

MTD of biweekly flavopiridol when given in conjunction with irinotecan hydrochloride, fluorouracil, and leucovorin

Outcome Time Frame:

8 weeks

Safety Issue:

Yes

Principal Investigator

Gary K. Schwartz

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01410

NCT ID:

NCT00042874

Start Date:

May 2002

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021