Stage III Lymphoepithelioma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage II Lymphoepithelioma of the Nasopharynx, Stage II Squamous Cell Carcinoma of the Nasopharynx, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx
Conditions
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.
Interventions
DRUGdocetaxel
Given IV
DRUGcisplatin
Given IV
DRUGcarboplatin
Given IV
DRUGfluorouracil
Given IV
RADIATION3-dimensional conformal radiation therapy
Undergo 3-dimensional conformal or intensity-modulated radiotherapy
RADIATIONintensity-modulated radiation therapy
Undergo 3-dimensional conformal or intensity-modulated radiotherapy
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression-free Survival (PFS) at 2 Years After Chemo-radiotherapy | up to 29 months (ie, 24 months post-chemoradiation) | Progression-free survival (PFS) means to remain alive without disease progression. Progression is defined as either the appearance of one or more new cancer lesions, or a ≥ 20% increase in the sum of the longest diameters (LD) of target cancer lesions, compared the same measurement obtained at the start of treatment. This outcome reported as the number of patients remaining alive at 2 years following chemo-radiotherapy without disease progression, a number without dispersion. |
| Median Progression-free Survival (PFS) | up to 127 months (includes treatment period of up to 5 months) | Progression-free survival (PFS) means to remain alive without disease progression. Progression is defined as either the appearance of one or more new cancer lesions, or a ≥ 20% increase in the sum of the longest diameters (LD) of target cancer lesions, compared the same measurement obtained at the start of treatment. This outcome reported as the median duration of PFS in months since chemo-radiotherapy, with full range. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to 127 months (includes treatment period of up to 5 months) | Overall survival (OS) was assessed as the duration of time that study participants remained alive after chemoradiotherapy. The outcome is reported as median OS (with full range). |
| Number of Participants With Adverse Events Resulting in Treatment Discontinuation | 8 months | Adverse events during treatment were assessed as whether they were definitely-, probably-, or possibly-related to protocol treatment (ie, adverse reaction). The outcome is reported as the number of participants who discontinued treatment due to an adverse reaction. |
| Number of Participants With Treatment Response | up to 29 months (ie, 24 months post-chemoradiation) | Participants who completed 1 cycle of docetaxel, cisplatin, and 5-fluorouracil (TPF) were evaluated for response. Response was assessed for lesions designated as target (TL) and non-target (NTL) as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The outcome is reported as a number without dispersion. TL Criterion: * CR: Disappearance of lesions * PR: 30% decrease in the sum of the longest diameter (LD) of lesions * PD: 20% increase in the sum of the LD of lesions, or any new lesion * SD: Neither sufficient shrinkage for PR nor sufficient increase for PD NTL Criterion: * CR: Disappearance of lesions and normalization of tumor marker level * PR / SD: Persistence of one or more lesion(s) and/or maintenance of tumor marker level above the normal limits (includes incomplete response / PR). * PD: Appearance of one or more new lesions and/or unequivocal progression of existing lesions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemoradiation for Nasopharyngeal Carcinoma Induction therapy as described, consisting of docetaxel, cisplatin, and fluorouracil Concurrent chemo-radiotherapy as described, 3-dimensional radiotherapy once daily for 6.5 to 7 weeks, with cisplatin weekly.
The total treatment course is up to 21 weeks. | 26 |
| Total | 26 |
Baseline characteristics
| Characteristic | Chemoradiation for Nasopharyngeal Carcinoma |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 51.3 years STANDARD_DEVIATION 12.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 26 |
| other Total, other adverse events | 24 / 26 |
| serious Total, serious adverse events | 5 / 26 |
Outcome results
Primary
Median Progression-free Survival (PFS)
Progression-free survival (PFS) means to remain alive without disease progression. Progression is defined as either the appearance of one or more new cancer lesions, or a ≥ 20% increase in the sum of the longest diameters (LD) of target cancer lesions, compared the same measurement obtained at the start of treatment. This outcome reported as the median duration of PFS in months since chemo-radiotherapy, with full range.
Time frame: up to 127 months (includes treatment period of up to 5 months)
Population: The outcome results are reported by baseline strata, ie, M0 (non-metastatic lesions) and M1 (metastatic lesions).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Chemoradiation for Nasopharyngeal Carcinoma | Median Progression-free Survival (PFS) | M0 (non-metastatic lesion) | 76 months |
| Chemoradiation for Nasopharyngeal Carcinoma | Median Progression-free Survival (PFS) | M1 (metastatic lesion) | 33 months |
Primary
Number of Participants With Progression-free Survival (PFS) at 2 Years After Chemo-radiotherapy
Progression-free survival (PFS) means to remain alive without disease progression. Progression is defined as either the appearance of one or more new cancer lesions, or a ≥ 20% increase in the sum of the longest diameters (LD) of target cancer lesions, compared the same measurement obtained at the start of treatment. This outcome reported as the number of patients remaining alive at 2 years following chemo-radiotherapy without disease progression, a number without dispersion.
Time frame: up to 29 months (ie, 24 months post-chemoradiation)
Population: The outcome results are reported by baseline strata, ie, M0 (non-metastatic lesions) and M1 (metastatic lesions).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Progression-free Survival (PFS) at 2 Years After Chemo-radiotherapy | M0 (non-metastatic lesion) | 18 Participants |
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Progression-free Survival (PFS) at 2 Years After Chemo-radiotherapy | M1 (metastatic lesion) | 4 Participants |
Secondary
Number of Participants With Adverse Events Resulting in Treatment Discontinuation
Adverse events during treatment were assessed as whether they were definitely-, probably-, or possibly-related to protocol treatment (ie, adverse reaction). The outcome is reported as the number of participants who discontinued treatment due to an adverse reaction.
Time frame: 8 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Adverse Events Resulting in Treatment Discontinuation | 1 Participants |
Secondary
Number of Participants With Treatment Response
Participants who completed 1 cycle of docetaxel, cisplatin, and 5-fluorouracil (TPF) were evaluated for response. Response was assessed for lesions designated as target (TL) and non-target (NTL) as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The outcome is reported as a number without dispersion. TL Criterion: * CR: Disappearance of lesions * PR: 30% decrease in the sum of the longest diameter (LD) of lesions * PD: 20% increase in the sum of the LD of lesions, or any new lesion * SD: Neither sufficient shrinkage for PR nor sufficient increase for PD NTL Criterion: * CR: Disappearance of lesions and normalization of tumor marker level * PR / SD: Persistence of one or more lesion(s) and/or maintenance of tumor marker level above the normal limits (includes incomplete response / PR). * PD: Appearance of one or more new lesions and/or unequivocal progression of existing lesions.
Time frame: up to 29 months (ie, 24 months post-chemoradiation)
Population: The outcome results are reported by baseline strata, ie, M0 (non-metastatic lesions) and M1 (metastatic lesions).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Treatment Response | CR for M0 (non-metastatic lesion) | 17 Participants |
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Treatment Response | PR for M0 (non-metastatic lesion) | 3 Participants |
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Treatment Response | SD for M0 (non-metastatic lesion) | 0 Participants |
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Treatment Response | PD for M0 (non-metastatic lesion) | 0 Participants |
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Treatment Response | CR for M1 (metastatic lesion) | 3 Participants |
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Treatment Response | PR for M1 (metastatic lesion) | 1 Participants |
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Treatment Response | SD for M1 (metastatic lesion) | 0 Participants |
| Chemoradiation for Nasopharyngeal Carcinoma | Number of Participants With Treatment Response | PD for M1 (metastatic lesion) | 0 Participants |
Secondary
Overall Survival (OS)
Overall survival (OS) was assessed as the duration of time that study participants remained alive after chemoradiotherapy. The outcome is reported as median OS (with full range).
Time frame: up to 127 months (includes treatment period of up to 5 months)
Population: The outcome results are reported by baseline strata, ie, M0 (non-metastatic lesions) and M1 (metastatic lesions). The per-protocol duration of treatment on study was 5 months, and the outcome is reported as OS (with full range) from that time.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Chemoradiation for Nasopharyngeal Carcinoma | Overall Survival (OS) | M0 (non-metastatic lesion) | 79 months |
| Chemoradiation for Nasopharyngeal Carcinoma | Overall Survival (OS) | M1 (metastatic lesion) | 76 months |