Phase II Trial of PS-341 (Bortezomib, NSC-681239) Followed by the Addition of Gemcitabine at Progression in Recurrent or Metastatic Nasopharyngeal Carcinoma
18 Years
N/A
Both
Recurrent Nasopharyngeal Cancer, Stage IV Nasopharyngeal Cancer
Trial Information
Phase II Trial of PS-341 (Bortezomib, NSC-681239) Followed by the Addition of Gemcitabine at Progression in Recurrent or Metastatic Nasopharyngeal Carcinoma
OBJECTIVES: Primary I. 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 I. Estimate 1-year progression-free survival and assess quantitative toxicities in
this group of patients treated with bortezomib.
II. 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.
III. Estimate 1-year overall survival of all patients treated with this regimen.
IV. 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.
V. 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.
Inclusion Criteria:
- 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
- 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
- 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Objective response rate (confirmed and unconfirmed, complete and partial response) based on the Response Evaluation Criteria in Solid Tumors (RECIST) in patients treated with bortezomib
Outcome Time Frame:
Up to 3 years
Safety Issue:
No
Principal Investigator
Stephen Shibata
Investigator Role:
Principal Investigator
Investigator Affiliation:
Southwest Oncology Group
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02690
NCT ID:
NCT00305734
Start Date:
August 2006
Completion Date:
Related Keywords:
- Recurrent Nasopharyngeal Cancer
- Stage IV Nasopharyngeal Cancer
- Nasopharyngeal Neoplasms
Name | Location |
|---|---|
| Southwest Oncology Group | San Antonio, Texas 78245 |
