Clinical trial NCT00896181: Phase 2 Sequential and Concurrent Chemoradiation for Advanced Nasopharyngeal Carcinoma (NPC)
Official title: A Phase 2 Study of Sequential and Concurrent Chemoradiation for Patients With Advanced Nasopharyngeal Carcinoma (NPC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stage II Lymphoepithelioma of the Nasopharynx
Stage II Squamous Cell Carcinoma of the Nasopharynx
Stage III Lymphoepithelioma of the Nasopharynx
Stage III Squamous Cell Carcinoma of the Nasopharynx
Stage IV Lymphoepithelioma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2009-05-11
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase 2 trial is studying whether giving a combination of docetaxel, cisplatin, and fluorouracil chemotherapy followed by the combination of cisplatin with radiation therapy works in treating patients with advanced nasopharyngeal cancer. Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving combination chemotherapy together with radiation therapy may kill more tumor cells.

Detailed description: PRIMARY OBJECTIVE:

• To establish the progression free survival rate at 2 years, using RECIST criteria, to induction treatment with docetaxel, cisplatin, and fluorouracil (TPF) followed by chemoradiotherapy of locoregionally advanced nasopharyngeal carcinoma (NPC)

SECONDARY OBJECTIVE:

• To evaluate complete response rates, safety and feasibility of TPF followed by chemoradiation in patients with NPC

OUTLINE: This is a single site study.

INDUCTION THERAPY: Patients receive docetaxel intravenously (IV) over 60 minutes on Day 1; cisplatin IV over 1 to 3 hours (or carboplatin IV over 30 minutes) on Day 1; and fluorouracil IV continuously over 24 hours on Days 1 to 5. Each cycle is 21 days, with treatment consisting of up to 3 cycles in the absence of disease progression or unacceptable toxicity.

CONCURRENT CHEMO-RADIOTHERAPY: Beginning within 3 to 6 weeks after initiating the last course of induction chemotherapy, patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily for 6.5 to 7 weeks. Patients also receive cisplatin IV over 1 hour (or carboplatin IV over 30 minutes) once weekly in weeks 1 to 6 in the absence of disease progression or unacceptable toxicity.

All study treatment is admininstered over the course of 21 weeks. After completion of study treatment, patients are followed periodically for 24 months.

Eligibility criteria: INCLUSION CRITERIA

* Histologically- or cytologically-confirmed nasopharyngeal carcinoma meeting the following criteria:

  * WHO type I, II, or III
  * Stage II to IVB disease (minimally T2a, N0, M0 or any T any, N1, M0)
  * Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
  * Prior diagnostic surgery(s) at the primary site or neck allowed provided there is still measurable disease present
  * Without known brain metastases
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
* Life expectancy \> 3 months
* Absolute neutrophil count (ANC) ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 times ULN
* Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 55 mL/min (NOTE: \* Patients with creatinine \> grade 1 but \< grade 3, hearing loss ≥ grade 2, and peripheral neuropathy ≥ grade 2 are eligible provided they receive carboplatin in place of cisplatin throughout study treatment)
* Hearing loss \< grade 2. Hearing loss grade 2 or greater attributable to tumor obstruction, when the bone conduction in the audiogram is consistent with less than grade 2, is permissible for cisplatin. Hearing loss will be evaluated by hearing in the best ear. If hearing loss is grade 2, patients are still eligible but should receive carboplatin throughout the protocol instead of cisplatin.
* Peripheral motor/sensory neuropathy \< grade 2. If peripheral neuropathy is grade 2, patients are still eligible but should receive carboplatin throughout the protocol instead of cisplatin.
* Fertile patients must use effective contraception prior to and during study treatment

EXCLUSION CRITERIA

* Uncontrolled intercurrent illness including, but not limited to, any of the following:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Psychiatric illness or social situations that preclude compliance with study requirements
  * Clinically-significant cardiovascular disease
  * Cerebrovascular accident within the past 6 months
  * Myocardial infarction or unstable angina within the past 6 months
  * New York Heart Association (NYHA) class II to IV congestive heart failure
  * Serious and inadequately controlled cardiac arrhythmia
  * Significant vascular disease (eg, aortic aneurysm, history of aortic dissection)
  * Clinically-significant peripheral vascular disease
* History of allergic reaction attributed to compounds of similar chemical or biologic composition to docetaxel, cisplatin, carboplatin, fluorouracil, bevacizumab, or other agents used in this study
* Known brain metastases
* Concurrent combination antiretroviral therapy for HIV-positive patients
* Prior chemotherapy or radiotherapy for nasopharyngeal carcinoma
* Pregnant or nursing

Primary outcomes:
measure: Number of Participants With Progression-free Survival (PFS) at 2 Years After Chemo-radiotherapy
timeFrame: up to 29 months (ie, 24 months post-chemoradiation)
measure: Median Progression-free Survival (PFS)
timeFrame: up to 127 months (includes treatment period of up to 5 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: up to 127 months (includes treatment period of up to 5 months)
measure: Number of Participants With Adverse Events Resulting in Treatment Discontinuation
timeFrame: 8 months
measure: Number of Participants With Treatment Response
timeFrame: up to 29 months (ie, 24 months post-chemoradiation)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Hospitals and Clinics
state: California
Study officials:
affiliation: Stanford University Hospitals and Clinics
name: Alexander Colevas
role: PRINCIPAL_INVESTIGATOR
References: