Know Cancer

or
forgot password

A Phase I Trial of Gemcitabine Followed by a Short Infusion of Flavopiridol in Patients With Solid Tumors


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

A Phase I Trial of Gemcitabine Followed by a Short Infusion of Flavopiridol in Patients With Solid Tumors


PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of gemcitabine and flavopiridol in patients with
solid tumors.

SECONDARY OBJECTIVES:

I. Determine the safety profile and toxic effects of this regimen in these patients.

II. Determine the pharmacokinetics of flavopiridol with and without gemcitabine in these
patients.

III. Determine, using pharmacodynamic assays, the activity of flavopiridol as a cdk
inhibitor in these patients.

IV. Determine, using pharmacodynamic assays, the markers of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Some patients receive an initial dose of alvocidib IV over 1-7 hours on day 1 (course 0).
Beginning 1 week later and for all subsequent courses, all patients receive gemcitabine
hydrochloride IV over 60-150 minutes on days 1 and 15 and alvocidib IV over 1-7 hours on
days 2 and 16. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and 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. Once
the MTD is determined, up to 10 additional patients receive treatment at that dose.

Patients are followed at 30 days after study completion.


Inclusion Criteria:



- Negative pregnancy test

- Fertile patients must use effective contraception

- No active infection

- No severe malnutrition

- No more than 2 prior chemotherapy regimens:

- Prior combined modality therapy (e.g., full-dose chemotherapy with
radiosensitizing chemotherapy and radiotherapy) is considered 1 prior regimen if
all therapy was delivered as part of 1 comprehensive treatment plan

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

- No other concurrent chemotherapy

- At least 6 months since prior radiotherapy to the lung parenchyma or mediastinum and
no evidence of radiation pneumonitis on chest CT scan

- At least 4 weeks since other prior radiotherapy and recovered

- No prior radiotherapy to more than 50% of marrow volume

- No concurrent radiotherapy

- Histologically confirmed solid tumor for which gemcitabine is a treatment option OR
for which no efficacious therapy exists

- Must meet criteria for 1 of the following:

- Measurable disease:

- At least 1 unidimensionally measurable lesion at least 20 mm by
conventional techniques OR at least 10 mm by spiral CT scan

- Nonmeasurable disease, including any of the following:

- Small lesions (less than 20 mm by conventional techniques OR less than 10
mm by spiral CT scan)

- Bone lesions

- Cytologically positive pleural or peritoneal disease

- Elevated tumor markers (e.g., carcinoembryonic antigen, CA 125, CA 19-9, or
other tumor marker)

- Multinodular or confluent nonmeasurable pulmonary, hepatic, adrenal,
intra-abdominal, or skin metastases

- No active CNS metastases

- Previously treated CNS metastases must be stable with no symptoms for 4
weeks after completion of treatment AND patient must be off steroid therapy
or on a stable dose for at least the past 2 weeks

- No known leptomeningeal metastases

- Performance status:

- ECOG 0-1

- Hematopoietic:

- 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 no greater than 2.5 times upper limit of normal

- Renal:

- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance at least 50 mL/min

- Cardiovascular:

- None of the following within the past 6 months:

- Myocardial infarction;

- Unstable angina;

- Transient ischemic attack;

- Cerebrovascular accident

- No new cardiac arrhythmia possibly related to cardiac ischemia;

- No large and potentially symptomatic pericardial effusion;

- No cardiac disease that would preclude study participation

- Pulmonary:

- No pulmonary embolism within the past 6 months;

- No large and potentially symptomatic pleural effusion;

- No pulmonary disease that would preclude study participation

- Gastrointestinal:

- No intractable emesis;

- No grade 2 or greater chronic diarrheal disease within the past 6 months

- Not pregnant or nursing

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Dose-limiting toxicity (DLT) graded by National Cancer Institute (NCI) Common Toxicity Criteria

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Geoffrey Shapiro

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00038

NCT ID:

NCT00072436

Start Date:

September 2003

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Dana-Farber Cancer InstituteBoston, Massachusetts  02115