Gemcitabine Hydrochloride and Alvocidib in Treating Patients With Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00072436
First received: November 4, 2003
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

This phase I trial is studying the side effects and best dose of gemcitabine hydrochloride and alvocidib in treating patients with solid tumors. Drugs used in chemotherapy, such as gemcitabine hydrochloride and alvocidib, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: gemcitabine hydrochloride
Drug: alvocidib
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Gemcitabine Followed by a Short Infusion of Flavopiridol in Patients With Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Dose-limiting toxicity (DLT) graded by National Cancer Institute (NCI) Common Toxicity Criteria [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Maximum tolerated dose, defined as one dose level below the dose that induces DLT in more than 1/6 patients [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Enrollment: 58
Study Start Date: September 2003
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment

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 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.

Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: alvocidib
Given IV
Other Names:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00072436

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: Geoffrey Shapiro Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00072436     History of Changes
Other Study ID Numbers: NCI-2009-00038, 6051, P30CA006516, U01CA062490, CDR0000339727
Study First Received: November 4, 2003
Last Updated: July 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Gemcitabine
Alvocidib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Growth Inhibitors
Growth Substances
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014