Bortezomib and Gemcitabine in Treating Patients With Recurrent or Metastatic Nasopharyngeal Cancer
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on March 21, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Head and Neck Cancer
Intervention: bortezomib (Drug); gemcitabine hydrochloride (Drug); chemotherapy (Procedure); enzyme inhibitor therapy (Procedure)
Phase: Phase 2
Status: Completed
Sponsored by: Southwest Oncology Group Official(s) and/or principal investigator(s):
Stephen I. Shibata, MD, Study Chair, Affiliation: Beckman Research Institute
Sai-Hong I. Ou, MD, PhD, Affiliation: Chao Family Comprehensive Cancer Center
Summary
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.
Clinical Details
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
Study design: Treatment, Open Label
Primary outcome: Response probability (confirmed and unconfirmed, complete and partial response)3-month progression-free survival rate
Secondary outcome: Progression-free survival rate at 6 months and 1 yearToxicity Response probability (confirmed and unconfirmed, complete and partial) 1-year overall survival Relationship between changes in EBV DNA level, NF-KappaB DNA binding activity, and methylation status of E-cadherin promoter with clinical outcomes
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
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
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: August 2006
Last updated: March 6, 2008
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