Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: vinorelbine ditartrate; Drug: gemcitabine hydrochloride; Drug: pegylated liposomal doxorubicin hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00006372

CWRU-1Y99

P30CA043703 (U.S. NIH Grant/Contract)

NCI-G00-1859

CWRU1Y99

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)