Bortezomib Plus Gemcitabine and Carboplatin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer - Full Text View

Sponsors and Collaborators:	California Cancer Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00052338

Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug and bortezomib may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining bortezomib with gemcitabine and carboplatin in treating patients who have advanced or recurrent non-small cell lung cancer.

Condition	Intervention	Phase
Lung Cancer Metastatic Cancer	Drug: bortezomib Drug: carboplatin Drug: gemcitabine hydrochloride	Phase I

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Carboplatin Gemcitabine hydrochloride Gemcitabine Bortezomib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study Of PS-341 In Combination With Gemcitabine And Carbloplatin In Selected Stage IIIB Or IV Non-Small Cell Lung Cancer

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

December 2002

Detailed Description:

OBJECTIVES:

Determine the safety and feasibility of combining bortezomib with gemcitabine and carboplatin in patients with advanced or recurrent non-small cell lung cancer.
Determine the maximum tolerated dose of bortezomib administered in combination with gemcitabine and carboplatin in these patients.
Correlate results from laboratory studies on patient tissue and serum specimens with potential predictors of response in patients treated with this regimen.
Determine, preliminarily, the response of patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of bortezomib.

Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 15-30 minutes on day 1, followed 1 hour later by bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with a clinical or radiographic response may continue receiving bortezomib beyond 6 courses.

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

Once the MTD is determined, at least 10 additional patients with chemotherapy-naive disease receive treatment as above with the MTD of bortezomib.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 25-34 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed non-small cell lung cancer
- Selected stage IIIB (malignant pleural effusion) or stage IV disease
- Recurrent disease after first-line therapy allowed
Patients who received prior platinum-based chemotherapy must have no disease progression during or within 3 months after completion of therapy
- Patients who are enrolled at the maximum tolerated dose must have chemotherapy-naïve disease
Evaluable disease
Asymptomatic brain metastases allowed if treated with surgical resection or radiotherapy, neurologically stable, and off steroids for at least 4 weeks

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Karnofsky 60-100%

Life expectancy

More than 3 months

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin no greater than than 1.5 mg/dL
AST no greater than 2.5 times upper limit of normal

Renal

Creatinine normal OR
Creatinine clearance at least 50 mL/min

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No peripheral neuropathy grade 2 or greater
No prior allergic reactions to compounds of similar chemical or biological composition to bortezomib or other agents used in this study
No concurrent ongoing or active infection
No other concurrent uncontrolled illness
No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent routine filgrastim (G-CSF)

Chemotherapy

See Disease Characteristics
No more than 1 prior chemotherapy regimen
At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered
No prior gemcitabine

Endocrine therapy

See Disease Characteristics

Radiotherapy

See Disease Characteristics
At least 4 weeks since prior radiotherapy and recovered

Surgery

See Disease Characteristics

Other

More than 30 days since prior investigational drugs
No prior bortezomib
No concurrent anticonvulsant therapy
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational or commercial agents or therapies with intent to treat malignancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052338

Locations

United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
University of California Davis Cancer Center
Sacramento, California, United States, 95817
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90033
Veterans Affairs Outpatient Clinic - Martinez
Martinez, California, United States, 94553

Sponsors and Collaborators

California Cancer Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:

Angela Davies, MD

University of California, Davis

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications of Results:

Davies AM, Ruel C, Lara PN, Lau DH, Gumerlock PH, Bold R, Shibata S, Lenz HJ, Schenkein DP, Gandara DR. The proteasome inhibitor bortezomib in combination with gemcitabine and carboplatin in advanced non-small cell lung cancer: a California Cancer Consortium Phase I study. J Thorac Oncol. 2008 Jan;3(1):68-74.

Study ID Numbers:	CDR0000258189, CCC-PHI-40, CHNMC-PHI-40, NCI-5856
Study First Received:	January 24, 2003
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00052338
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
malignant pleural effusion

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Bortezomib
Pleural Effusion, Malignant
Carboplatin
Recurrence
Carcinoma
Pleural Effusion

Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Neoplasm Metastasis
Gemcitabine
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors

Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Neoplasms
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009