Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

Phase I Trial of Combination Pegylated Liposomal Doxorubicin (Doxil), Vinorelbine, and Gemcitabine

RATIONALE: 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.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating patients who have advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: pegylated liposomal doxorubicin hydrochloride; Drug: vinorelbine ditartrate

Detailed Description

OBJECTIVES:

• Determine the pharmacokinetic profile of gemcitabine, doxorubicin HCl liposome, and vinorelbine in patients with advanced solid tumors.
• Determine the maximum tolerated dose of this regimen in these patients.
• Determine the toxicity profile of this regimen in these patients.

OUTLINE: This is a dose escalation study.

Patients receive doxorubicin HCl liposome IV over 1-2.5 hours on day 1, gemcitabine IV over 30 minutes on days 1 and 8, and vinorelbine IV over 6-10 minutes on days 1 and 15. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome, gemcitabine, and vinorelbine 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.

Patients are followed every 3 months for up to 1 year.

PROJECTED ACCRUAL: Approximately 9-24 patients will be accrued for this study within 12-18 months.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-5055
      • Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive 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 confirmed solid tumor not amenable to curative surgery, radiotherapy, or chemotherapy
• No brain metastases or primary brain tumors

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC at least 3,500/mm3
• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• Hemoglobin greater than 10 g/dL

Hepatic:

• Bilirubin no greater than 1.2 mg/dL
• AST and/or ALT less than 2.5 times upper limit of normal (ULN)
• PT no greater than ULN (anticoagulant independent)

Renal:

• Creatinine no greater than 1.5 mg/dL AND/OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• LVEF at least 45% by MUGA or echocardiogram

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior bone marrow or peripheral blood stem cell transplantation following high dose chemotherapy
• At least 3 weeks since prior biologic therapy for cancer and recovered
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy:

• See Disease Characteristics
• See Biologic therapy
• No more than 1 prior chemotherapy regimen
• No prior vinca alkaloids
• Prior anthracycline allowed if total dose no greater than 300 mg/m2
• At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or carmustine) and recovered

Endocrine therapy:

• At least 3 weeks since prior endocrine therapy for cancer and recovered

Radiotherapy:

• See Disease Characteristics
• No more than 1 prior radiotherapy regimen
• At least 4 weeks since prior large field radiotherapy
• At least 3 weeks since prior radiotherapy for cancer and recovered

Surgery:

• Not specified

Study Plan

How is the study designed?

Design Details

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

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Beth A. Overmoyer, MD, FACP, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2000
• Primary Completion (Actual): April 1, 2003
• Study Completion (Actual): February 1, 2005

Study Registration Dates

• First Submitted: October 4, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 11, 2010
• Last Update Submitted That Met QC Criteria: June 9, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: 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; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Gemcitabine; Doxorubicin; Liposomal doxorubicin; Vinorelbine
• Other Study ID Numbers: CWRU1Y99; P30CA043703 (U.S. NIH Grant/Contract); CWRU-1Y99; NCI-G00-1859