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”

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.

Study Type: Interventional

Study Design: Treatment, Open Label

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.

Primary:

• Response probability (confirmed and unconfirmed, complete and partial response) No
• 3-month progression-free survival rate No

Secondary:

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

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

Lead Sponsor: Southwest Oncology Group

Tammy Walker Cancer Center at Salina Regional Health Center

Salina Kansas 67401 United States

MidMichigan Medical Center - Midland

Midland Michigan 48670 United States

Great Falls Montana 59405 United States

Billings Clinic Cancer Center

Billings Montana 59107-5100 United States

Bozeman Deaconess Hospital

Bozeman Montana 59715 United States

CCOP - Montana Cancer Consortium

Billings Montana 59101 United States

Community Medical Center

Missoula Montana 59801 United States

Deaconess Billings Clinic - Downtown

Billings Montana 59107-7000 United States

Glacier Oncology, PLLC

Kalispell Montana 59901 United States

Great Falls Clinic

Great Falls Montana 59405 United States

Guardian Oncology and Center for Wellness

Missoula Montana 59804 United States

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings Montana 59101 United States

Kalispell Medical Oncology

Kalispell Montana 59901 United States

Kalispell Regional Medical Center

Kalispell Montana 59901 United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

Missoula Montana 59807 United States

Montana Cancer Specialists at Montana Cancer Center

Missoula Montana 59807-7877 United States

Northern Rockies Radiation Oncology Center

Billings Montana 59101 United States

St. James Community Hospital

Butte Montana 59701 United States

St. Peter's Hospital

Helena Montana 59601 United States

St. Vincent Healthcare

Billings Montana 59101 United States

Wayne Memorial Hospital, Incorporated

Goldsboro North Carolina 27534 United States

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan Wyoming 82801 United States

Overall Clinical Trial Officials and Contacts

Stephen I. Shibata, MD Study Chair Beckman Research Institute  

Information obtained from ClinicalTrials.gov on July 18, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00305734

Study ID Number: CDR0000462635

ClinicalTrials.gov Identifier: NCT00305734

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database