Clinical trial NCT00014456: Combination Chemotherapy Plus Filgrastim in Treating Patients With Advanced Solid Tumors
Official title: A Dose-Escalation Trial Of The Combination Of Docetaxel, Gemcitabine And Filgrastim (NEUPOGEN) For The Treatment Of Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Keywords: 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
ovarian sarcoma
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
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Determine the maximal tolerated dose of docetaxel in combination with gemcitabine given intravenously every 2 weeks with pegfilgrastim support
timeFrame: Four years
measure: Define dose limiting adverse events associated with the combination
timeFrame: Four years
Secondary outcomes:
measure: Objective antitumor response
timeFrame: Four years
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Norris Cotton Cancer Center
name: Konstantin H. Dragnev, MD
role: STUDY_CHAIR
References:
citation: Dragnev KH, Hardin SB, Pipas JM, Davis TH, Rigas JR. A dose escalation trial of biweekly docetaxel and gemcitabine with filgrastim or pegfilgrastim for the treatment of patients with advanced solid tumors. Chemotherapy. 2010;56(2):135-41. doi: 10.1159/000313526. Epub 2010 Apr 20.