Back to results

Phase 2 Sequential and Concurrent Chemoradiation for Advanced Nasopharyngeal Carcinoma (NPC)

Primary Purpose

Stage II Lymphoepithelioma of the Nasopharynx, Stage II Squamous Cell Carcinoma of the Nasopharynx, Stage III Lymphoepithelioma of the Nasopharynx

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

docetaxel

cisplatin

carboplatin

fluorouracil

3-dimensional conformal radiation therapy

intensity-modulated radiation therapy

About this trial

This is an interventional treatment trial for Stage II Lymphoepithelioma of the Nasopharynx

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Stanford University Hospitals and Clinics

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chemoradiation for Nasopharyngeal Carcinoma

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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).

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.

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.

Full Information

NCT ID

NCT00896181

First Posted

May 7, 2009

Last Updated

March 10, 2021

Sponsor

Stanford University

1. Study Identification

Unique Protocol Identification Number

NCT00896181

Brief Title

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

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

December 10, 2008 (Actual)

Primary Completion Date

January 3, 2020 (Actual)

Study Completion Date

December 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Stanford University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Chemoradiation for Nasopharyngeal Carcinoma

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

docetaxel

Other Intervention Name(s)

RP 56976, Taxotere, TXT

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

cisplatin

Other Intervention Name(s)

CACP, CDDP, CPDD, DDP

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

carboplatin

Other Intervention Name(s)

Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Other Intervention Name(s)

5-fluorouracil, 5-Fluracil, 5-FU

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

3-dimensional conformal radiation therapy

Other Intervention Name(s)

3D conformal radiation therapy, 3D-CRT

Intervention Description

Undergo 3-dimensional conformal or intensity-modulated radiotherapy

Intervention Type

Radiation

Intervention Name(s)

intensity-modulated radiation therapy

Other Intervention Name(s)

IMRT

Intervention Description

Undergo 3-dimensional conformal or intensity-modulated radiotherapy

Primary Outcome Measure Information:

Title

Number of Participants With Progression-free Survival (PFS) at 2 Years After Chemo-radiotherapy

Description

Time Frame

up to 29 months (ie, 24 months post-chemoradiation)

Title

Median Progression-free Survival (PFS)

Description

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)

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

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)

Title

Number of Participants With Adverse Events Resulting in Treatment Discontinuation

Description

Time Frame

8 months

Title

Number of Participants With Treatment Response

Description

Time Frame

up to 29 months (ie, 24 months post-chemoradiation)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexander Colevas

Organizational Affiliation

Stanford University Hospitals and Clinics

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University Hospitals and Clinics

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Phase 2 Sequential and Concurrent Chemoradiation for Advanced Nasopharyngeal Carcinoma (NPC)

We'll reach out to this number within 24 hrs