Combination Chemotherapy Plus Filgrastim in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Dose-Escalation Trial Of The Combination Of Docetaxel, Gemcitabine And Filgrastim (NEUPOGEN) For The Treatment Of Patients With Advanced Solid Tumors

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

Intervention / Treatment
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* Biological: filgrastim
* Drug: docetaxel
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: docetaxel|nan|
|Drug: gemcitabine hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximal tolerated dose of docetaxel in combination with gemcitabine given intravenously every 2 weeks with pegfilgrastim support |  | Four years | 
| Define dose limiting adverse events associated with the combination |  | Four years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective antitumor response |  | Four years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian sarcoma, stage IV breast cancer, recurrent breast cancer, stage IV gastric cancer, recurrent gastric cancer, metastatic osteosarcoma, recurrent non-small cell lung cancer, stage II pancreatic cancer, stage III pancreatic cancer, recurrent pancreatic cancer, stage II esophageal cancer, stage III esophageal cancer, stage IV esophageal cancer, recurrent esophageal cancer, chondrosarcoma, recurrent adult soft tissue sarcoma, stage IV ovarian epithelial cancer, recurrent ovarian epithelial cancer, extensive stage small cell lung cancer, recurrent small cell lung cancer, recurrent osteosarcoma, recurrent bladder cancer, stage IV bladder cancer, stage IV prostate cancer, recurrent prostate cancer, stage IV melanoma, recurrent melanoma, stage IV non-small cell lung cancer, stage IV salivary gland cancer, recurrent salivary gland cancer, classic Kaposi sarcoma, AIDS-related Kaposi sarcoma, recurrent Kaposi sarcoma, recurrent metastatic squamous neck cancer with occult primary, stage IV ovarian germ cell tumor, recurrent ovarian germ cell tumor, stage IV uterine sarcoma, recurrent uterine sarcoma, borderline ovarian surface epithelial-stromal tumor, recurrent carcinoma of unknown primary, metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx, recurrent squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, recurrent lymphoepithelioma of the nasopharynx, recurrent squamous cell carcinoma of the nasopharynx, stage IV lymphoepithelioma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, recurrent lymphoepithelioma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, stage IV lymphoepithelioma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity, recurrent inverted papilloma of the paranasal sinus and nasal cavity, recurrent midline lethal granuloma of the paranasal sinus and nasal cavity, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity, stage IV inverted papilloma of the paranasal sinus and nasal cavity, stage IV midline lethal granuloma of the paranasal sinus and nasal cavity, stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent verrucous carcinoma of the oral cavity, stage IV verrucous carcinoma of the oral cavity, recurrent basal cell carcinoma of the lip, stage IV basal cell carcinoma of the lip, recurrent mucoepidermoid carcinoma of the oral cavity, stage IV mucoepidermoid carcinoma of the oral cavity, recurrent adenoid cystic carcinoma of the oral cavity, stage IV adenoid cystic carcinoma of the oral cavity, stage IV adult soft tissue sarcoma, stage IV pancreatic cancer