Combination Chemotherapy Plus Filgrastim in Treating Patients With Advanced Solid Tumors

Dartmouth Health

Status and phase: Completed; Phase 1

Conditions: Breast Cancer; Esophageal Cancer; Melanoma (Skin); Lung Cancer; Ovarian Cancer; Carcinoma of Unknown Primary; Sarcoma; Bladder Cancer; Gastric Cancer; Head and Neck Cancer; Prostate Cancer; Pancreatic Cancer

Treatments: Drug: gemcitabine hydrochloride; Biological: filgrastim; Drug: docetaxel

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00014456

NCI-G01-1933

D9933

DMS-9933

P30CA023108 (U.S. NIH Grant/Contract)

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. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

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

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of docetaxel in combination with gemcitabine and filgrastim (G-CSF) in patients with advanced solid tumors.
• Determine the dose-limiting toxicity associated with this regimen in these patients.
• Assess the objective anti-tumor response in patients treated with this regimen.
• Determine fatigue and blood cytokines in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of docetaxel.

Patients receive docetaxel IV over 1 hour followed by gemcitabine IV over 30 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 2 and continuing until blood counts recover. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of docetaxel 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.

Fatigue is assessed at baseline and then at weeks 2, 5, 7, and 9 during therapy.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 15-22 months.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed advanced solid tumor that is not curable by surgery or radiotherapy

  • Sarcoma
  • Melanoma
  • Carcinoma of unknown primary
  • Pancreatic cancer
  • Lung cancer
  • Ovarian cancer
  • Breast cancer
  • Bladder cancer
  • Gastric cancer
  • Esophageal cancer
  • Prostate cancer
  • Head and neck cancer

• No hematopoietic or lymphoid tumors

• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• Karnofsky 60-100%
• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin normal
• AST and/or ALT no greater than 5 times upper limit of normal (ULN) if alkaline phosphatase no greater than ULN OR
• Alkaline phosphatase no greater than 5 times ULN if AST and ALT no greater than ULN OR
• AST and/or ALT no greater than 1.5 times ULN if alkaline phosphatase no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 2 times ULN OR
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• No congestive heart failure
• No unstable angina

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No known sensitivity to E. coli-derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 2 weeks since prior cytotoxic anti-tumor therapy (4 weeks for nitrosourea or mitomycin) and recovered
• No prior docetaxel or gemcitabine

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy and recovered

Surgery:

• Not specified

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)