Bortezomib and Gemcitabine in Treating Patients With Recurrent or Metastatic Nasopharyngeal Cancer - Full Text View

Sponsors and Collaborators:	Southwest Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00305734

Purpose

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with gemcitabine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with gemcitabine works in treating patients with recurrent or metastatic nasopharyngeal cancer.

Condition	Intervention	Phase
Head and Neck Cancer	Drug: bortezomib Drug: gemcitabine hydrochloride	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II Trial of PS-341 (Bortezomib, NSC-681239) Followed by the Addition of Gemcitabine at Progression in Recurrent or Metastatic Nasopharyngeal Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Bortezomib

U.S. FDA Resources

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

Primary Outcome Measures:

Response probability (confirmed and unconfirmed, complete and partial response) [ Designated as safety issue: No ]
3-month progression-free survival rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival rate at 6 months and 1 year [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Response probability (confirmed and unconfirmed, complete and partial) [ Designated as safety issue: No ]
1-year overall survival [ Designated as safety issue: No ]
Relationship between changes in EBV DNA level, NF-KappaB DNA binding activity, and methylation status of E-cadherin promoter with clinical outcomes [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	August 2006
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Assess the response probability (confirmed and unconfirmed, complete and partial responses) and 3-month progression-free survival rate in patients with metastatic or recurrent nasopharyngeal carcinoma (NPC) who are treated with bortezomib.

Secondary

Estimate 1-year progression-free survival and assess quantitative toxicities in this group of patients treated with bortezomib.
Evaluate the response probability (confirmed and unconfirmed, complete and partial) in the subset of patients who progress on bortezomib, with measurable disease at the time of progression, and go on to receive bortezomib and gemcitabine hydrochloride combination therapy.
Estimate 1-year overall survival of all patients treated with this regimen.
Estimate 6-month progression-free survival from the start of combination therapy and assess quantitative toxicities in the subset of patients who progress on bortezomib and receive combination therapy.
Explore, in a preliminary manner, the relationship between changes in Epstein-Barr virus DNA level, NF-kB DNA-binding activity, and methylation status of E-cadherin promoter with clinical outcomes.

OUTLINE: This is a multicenter study of bortezomib.

Patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses of treatment with bortezomib.

Patients who experience disease progression on single-agent bortezomib and did not receive prior gemcitabine hydrochloride may begin combination therapy within 10-28 days of the last dose of bortezomib. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and bortezomib IV on days 1, 4, 8, 11. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a CR receive 2 additional courses beyond the confirmed CR.

After the completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 50 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 confirmed nasopharyngeal carcinoma (NPC) of one of the following subtypes:
- Non-keratinizing (WHO type II)
- Undifferentiated (WHO type III)
Disease meets one of the following stage criteria:
- Stage IVC at diagnosis
- Persisted, metastasized, or recurred after definitive surgery, radiotherapy, and/or chemotherapy
Measurable disease
- If only measurable disease is within a prior radiation therapy port, disease progression must be clearly demonstrated
No known CNS metastases

PATIENT CHARACTERISTICS:

Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL/min
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Bilirubin normal
SGOT or SGPT ≤ 2.5 times ULN
Zubrod performance status 0-2
No peripheral neuropathy > grade 1
No prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient has been disease-free for 5 years
Not pregnant or nursing
Fertile patients must use effective contraception
More than 6 months since prior myocardial infarction
No New York Heart Association class III or IV cardiac problems
No uncontrolled angina
No severe uncontrolled ventricular arrhythmias
No acute ischemia by ECG
No active conduction system abnormalities
No known hypersensitivity to bortezomib, boron, or mannitol

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior therapy with gemcitabine hydrochloride, bortezomib, or other proteasome inhibitors
- No more than 28 days since discontinuation of single-agent bortezomib
- Patients with prior gemcitabine hydrochloride treatment are eligible for single-agent bortezomib treatment but NOT for combination treatment
No more than one prior chemotherapy regimen for the treatment of metastatic or recurrent NPC
- At least 28 days since prior treatment and recovered
At least 24 weeks since prior adjuvant chemotherapy
At least 24 weeks since prior chemotherapy as a radiosensitizer for initial locally advanced disease
At least 28 days since prior radiotherapy and recovered
At least 28 days since prior surgery and recovered
No other concurrent therapy for NPC, including any of the following:
- Radiotherapy
- Chemotherapy
- Immunotherapy
- Biologic therapy
- Other investigational drugs
- Gene therapy
No colony-stimulating factor therapy during the first course of study therapy
No concurrent highly active antiretroviral therapy (HAART) in HIV-positive patients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305734

Locations

United States, Kansas
Tammy Walker Cancer Center at Salina Regional Health Center
Salina, Kansas, United States, 67401
United States, Michigan
MidMichigan Medical Center - Midland
Midland, Michigan, United States, 48670
United States, Montana

Great Falls, Montana, United States, 59405
Billings Clinic Cancer Center
Billings, Montana, United States, 59107-5100
Bozeman Deaconess Hospital
Bozeman, Montana, United States, 59715
Guardian Oncology and Center for Wellness
Missoula, Montana, United States, 59804
Community Medical Center
Missoula, Montana, United States, 59801
Deaconess Billings Clinic - Downtown
Billings, Montana, United States, 59107-7000
Glacier Oncology, PLLC
Kalispell, Montana, United States, 59901
Great Falls Clinic
Great Falls, Montana, United States, 59405
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, United States, 59101
Kalispell Medical Oncology
Kalispell, Montana, United States, 59901
Kalispell Regional Medical Center
Kalispell, Montana, United States, 59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, United States, 59807
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, United States, 59807-7877
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
St. James Community Hospital
Butte, Montana, United States, 59701
St. Peter's Hospital
Helena, Montana, United States, 59601
St. Vincent Healthcare
Billings, Montana, United States, 59101
United States, North Carolina
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
United States, Wyoming
Welch Cancer Center at Sheridan Memorial Hospital
Sheridan, Wyoming, United States, 82801

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Stephen I. Shibata, MD	Beckman Research Institute
Investigator:	Sai-Hong I. Ou, MD, PhD	Chao Family Comprehensive Cancer Center

More Information

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000462635, SWOG-S0506
Study First Received:	March 21, 2006
Last Updated:	May 23, 2008
ClinicalTrials.gov Identifier:	NCT00305734 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

recurrent nasopharyngeal cancer
stage IV nasopharyngeal cancer

Study placed in the following topic categories:

Antimetabolites
Anti-Infective Agents
Otorhinolaryngologic Neoplasms
Otorhinolaryngologic Diseases
Nasopharyngeal Carcinoma
Immunologic Factors
Bortezomib
Disease Progression
Pharyngeal Neoplasms
Immunosuppressive Agents

Antiviral Agents
Pharyngeal Diseases
Recurrence
Nasopharyngeal Neoplasms
Protease Inhibitors
Carcinoma
Radiation-Sensitizing Agents
Head and Neck Neoplasms
Stomatognathic Diseases
Gemcitabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Otorhinolaryngologic Neoplasms
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Pharyngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms by Site
Therapeutic Uses
Nasopharyngeal Diseases

Gemcitabine
Otorhinolaryngologic Diseases
Bortezomib
Enzyme Inhibitors
Pharyngeal Diseases
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Protease Inhibitors
Neoplasms
Radiation-Sensitizing Agents
Head and Neck Neoplasms
Stomatognathic Diseases

ClinicalTrials.gov processed this record on August 24, 2009