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

A Phase 2 Study of Sequential and Concurrent Chemoradiation for Patients With Advanced Nasopharyngeal Carcinoma (NPC)

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.

Study Overview

• Status: Completed
• 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
• Intervention / Treatment: Drug: fluorouracil; Drug: cisplatin; Drug: carboplatin; Drug: docetaxel; Radiation: 3-dimensional conformal radiation therapy; Radiation: intensity-modulated radiation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Chemoradiation for Nasopharyngeal Carcinoma; 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.

Drug: fluorouracil; Given IV; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil; Drug: cisplatin; Given IV; Other Names: CDDP; DDP; CACP; CPDD; Drug: carboplatin; Given IV; Other Names: Carboplat; CBDCA; JM-8; Paraplatin; Paraplat; Drug: docetaxel; Given IV; Other Names: Taxotere; RP 56976; TXT; Radiation: 3-dimensional conformal radiation therapy; Undergo 3-dimensional conformal or intensity-modulated radiotherapy; Other Names: 3D-CRT; 3D conformal radiation therapy; Radiation: intensity-modulated radiation therapy; Undergo 3-dimensional conformal or intensity-modulated radiotherapy; Other Names: IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 29 months (ie, 24 months post-chemoradiation)
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.	up to 127 months (includes treatment period of up to 5 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	up to 127 months (includes treatment period of up to 5 months)
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.	8 months
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.	up to 29 months (ie, 24 months post-chemoradiation)

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Alexander Colevas, Stanford University Hospitals and Clinics

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2008
• Primary Completion (Actual): January 3, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: May 7, 2009
• First Submitted That Met QC Criteria: May 8, 2009
• First Posted (Estimate): May 11, 2009

Study Record Updates

• Last Update Posted (Actual): April 6, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Squamous Cell; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Carcinoma, Squamous Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Carboplatin; Cisplatin; Fluorouracil
• Other Study ID Numbers: IRB-15411; 8209 (Other Identifier: CTEP); NCI-2009-01162 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000671087; ENT0025 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No