Gemcitabine Plus Flavopiridol in Treating Patients With Advanced Solid Tumors

A Phase I Trial Of Gemcitabine Followed By Flavopiridol In Patients With Solid Tumors

Phase I trial to study the effectiveness of gemcitabine plus flavopiridol in treating patients who have advanced solid tumors. Drugs used in chemotherapy 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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: alvocidib; Drug: gemcitabine hydrochloride

Detailed Description

OBJECTIVES:

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

II. Determine the toxicity and safety profile of this regimen in these patients.

III. Determine the pharmacokinetic profile of this regimen in this patient population.

OUTLINE: This is a dose-escalation study.

Patients receive gemcitabine IV over 1-2.5 hours on days 1 and 8 and flavopiridol IV continuously over 24 hours on days 2 and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine and flavopiridol until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 6-58 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically proven solid tumor for which gemcitabine is a treatment option or for which no effective therapy exists
• Previously untreated disease allowed
• No large and potentially symptomatic pericardial effusion or undrained pleural effusion (with or without pleurodesis)
• No CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm3
• Platelet count at least 100,000/mm3
• No prior thrombotic events

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No clinically significant cardiac disease
• No prior deep venous thrombus
• No prior arterial vascular event
• No prior myocardial infarction
• No unstable angina
• No prior transient ischemic attack or cerebrovascular accident
• No cardiac arrhythmias that could be related to cardiac ischemia

Pulmonary:

• No clinically significant pulmonary disease
• No history of pulmonary embolism

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• No severe malnutrition or intractable emesis
• No chronic diarrheal disease within the past 6 months

PRIOR CONCURRENT THERAPY:

Chemotherapy:

• No more than 1 prior chemotherapy regimen
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Prior gemcitabine or flavopiridol allowed
• No other concurrent chemotherapy

Radiotherapy:

• At least 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy to more than 50% of bone marrow
• No concurrent radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm I; Patients receive gemcitabine IV over 1-2.5 hours on days 1 and 8 and flavopiridol IV continuously over 24 hours on days 2 and 9. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine and flavopiridol until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Drug: alvocidib; Drug: gemcitabine hydrochloride

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Study Chair: Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: January 6, 2001
• First Submitted That Met QC Criteria: October 14, 2003
• First Posted (Estimate): October 15, 2003

Study Record Updates

• Last Update Posted (Estimate): February 28, 2013
• Last Update Submitted That Met QC Criteria: February 27, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Gemcitabine; Alvocidib
• Other Study ID Numbers: 00-166; U01CA062490 (U.S. NIH Grant/Contract); P30CA006516 (U.S. NIH Grant/Contract); DFCI-00166; NCI-24; CDR0000068344 (Registry Identifier: PDQ (Physician Data Query))