A Pilot Study of Flavopiridol in Patients With Advanced Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Pilot Study of Flavopiridol in Patients With Advanced Solid Tumors
PRIMARY OBJECTIVES:
I. Determine the toxicity profile and dose-limiting toxicity of flavopiridol (alvocidib) in
patients with locally advanced or metastatic solid tumors.
II. Determine the maximum tolerated dose of this drug in these patients.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
II. Determine the immunomodulatory effects of this drug in these patients. III. Determine
pharmacogenomics of this drug, using peripheral blood mononuclear cells, in patients who
experience clinical response.
OUTLINE: This is a pilot, dose-escalation study.
Patients receive alvocidib intravenously (IV) over 4½ hours once weekly in weeks 1-4.
Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or
unacceptable toxicity. Patients achieving stable disease after 4 courses of therapy
discontinue study treatment. Patients who achieve complete remission (CR) receive 1
additional course of therapy beyond documentation of CR. Cohorts of 3-6 patients receive
escalating doses of alvocidib 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. A total of 10 patients are treated at the MTD.
After completion of study treatment, patients are followed within 4 weeks.
Inclusion Criteria:
- Histologically or cytologically confirmed solid tumor
- Locally advanced or metastatic disease for which curative treatment does not
exist or is no longer effective
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan
- No previously irradiated* measurable lesion unless lesion demonstrates
progressive disease OR there are other measurable lesions outside the
irradiated* field
- The following are not considered measurable disease:
- Bone lesions
- Leptomeningeal disease
- Ascites
- Pleural or pericardial effusion
- Lymphangitis cutis/pulmonis
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
- No uncontrolled brain metastases
- Performance status - ECOG 0-1
- At least 6 months
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- AST and ALT ≤ 2.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- Creatinine ≤ 1.5 times ULN
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No uncontrolled cardiac arrhythmia
- No uncontrolled hypertension
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to flavopiridol
- No ongoing or active infection
- No uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
- More than 12 weeks since prior hepatic arterial chemoembolization
- More than 4 weeks since prior systemic chemotherapy
- No prior flavopiridol
- See Disease Characteristics
- More than 12 weeks since prior radioactive metaiodobenzylguanidine (MIBG)
- More than 4 weeks since prior external beam radiotherapy
- Recovered from all prior tumor-specific therapy
- More than 4 weeks since prior investigational tumor-specific therapy
- Concurrent octreotide for control of carcinoid syndrome allowed
- No concurrent combination anti-retroviral therapy for HIV-positive patients
- No other concurrent tumor-specific therapy
- No other concurrent investigational therapy
- No other concurrent anticancer therapy
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Adverse events of dose escalated alvocidib administered in patients with advanced solid tumors
Outcome Description:
Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Outcome Time Frame:
At weeks 1-4, 7-10, 11 or 12, and within 4 weeks after the completion of study treatment
Safety Issue:
Yes
Principal Investigator
Manisha Shah
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ohio State University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00135
NCT ID:
NCT00112684
Start Date:
February 2006
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| Ohio State University Medical Center | Columbus, Ohio 43210 |
