Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Bortezomib and Gemcitabine in Treating Patients With Recurrent or Metastatic Nasopharyngeal Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	SWOG-S0506 S0506, NCT00305734

Objectives

Primary

1. 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

1. Estimate 1-year progression-free survival and assess quantitative toxicities in this group of patients treated with bortezomib.
2. 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.
3. Estimate 1-year overall survival of all patients treated with this regimen.
4. 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.
5. 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.

Entry 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

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

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

Expected Enrollment

A total of 50 patients will be accrued for this study.

Outcomes

Response probability (confirmed and unconfirmed, complete and partial response)
3-month progression-free survival rate

Progression-free survival rate at 6 months and 1 year
Toxicity
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

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.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Stephen Shibata, MD, Protocol chair		Ph: 626-359-8111 ext. 62307; 800-826-4673 Email: sshibata@coh.org
Sai-Hong Ou, MD, PhD, Protocol co-chair		Ph: 714-456-8104 Email: siou@uci.edu

Registry Information
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
Trial Start Date		2006-08-15
Trial Completion Date		2007-07-01
Registered in ClinicalTrials.gov		NCT00305734
Date Submitted to PDQ		2005-12-06
Information Last Verified		2006-12-16
NCI Grant/Contract Number		CA32102

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