Study of Combination of Sorafenib With Cisplatin and 5-fluorouracil as First-line Treatment of Recurrence After Radiotherapy Patients Who Failed With Radiotherapy in Recurrent or Metastatic Nasopharyngeal Carcinoma (NPC)

Phase II Study of Combination of Sorafenib With Cisplatin and 5-fluorouracil as First-line Treatment of Recurrence After Radiotherapy Patients Who Are Failure of Radiotherapy in Recurrent or Metastatic Nasopharyngeal Carcinoma (NPC)

This study is a phase II clinical study. Recurrence after radiotherapy patients who are failure of radiotherapy in recurrent or metastatic nasopharyngeal carcinoma (NPC) were treated by cisplatin and 5-fluorouracil with Sorafenib as first-line treatment. The objective response(complete response (CR) + partial response (PR)), Disease Control Rate , safety profile, tolerability will be evaluated according to World Health Organization (WHO) criteria.

Study Overview

• Status: Completed
• Conditions: Nasopharyngeal Neoplasms
• Intervention / Treatment: Drug: Sorafenib plus Cisplatin and 5-fluorouracil

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Cancer Center of Sun-Yat Sen University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age > 18 years
2. ECOG Performance Status of 0 or 1
3. Life expectancy of at least 12 weeks
4. Pathologically confirmed nasopharyngeal carcinoma
5. Experience of treatment failure with radiotherapy for recurrent or metastatic NPC
6. More than 3 weeks must have elapsed since previous radiotherapy
7. Biomarkers measuring including pERK, EGFR of original diagnostic paraffin-embedded tumor samples; VEGF of pre-dose and post-dose plasma samples.
8. Subjects with at least one (for RECIST) measurable lesion (Tumor lesions that are situated in a previously irradiated area could not be considered measurable)

9. Adequate bone marrow, liver and renal functions as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

   • Hemoglobin > 9.0 g/dl
   • Absolute neutrophil count (ANC) > 1,500/mm3
   • Platelet count > 100,000/μl
   • Total bilirubin < 1.5 times the upper limit of normal
   • ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer), Alkaline phosphatase < 4 x ULN ,PT-INR/PTT < 1.5 x upper limit of normal, Serum creatinine < 1.5 x upper limit of normal
10. Signed and dated informed consent before the start of specific protocol procedures

Exclusion Criteria:

1. History of cardiac disease: congestive heart failure > NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
2. History of HIV infection
3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
4. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
5. History of organ allograft the organ allograft may be allowed as protocol specific.
6. Patients with evidence or history of bleeding diatheses
7. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
8. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial.
9. Patients unable to swallow oral medications
10. Prior use of farnesyl transferase, Raf kinase, or MEK inhibitors
11. Investigational drug therapy outside of this trial during or within 4 weeks of study entry
12. Prior exposure to the study drug

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: 1; Sorafenib with Cisplatin and 5-fluorouracil as first-line treatment of recurrence after radiotherapy patients who failed with radiotherapy in recurrent or metastatic nasopharyngeal carcinoma (NPC)

Drug: Sorafenib plus Cisplatin and 5-fluorouracil; Sorafenib with Cisplatin and 5-fluorouracil as first-line treatment of recurrence after radiotherapy patients who failed with radiotherapy in recurrent or metastatic nasopharyngeal carcinoma (NPC); Sorafenib 400 mg bid per daily . Every 21-day cycles.; Cisplatin 80 mg/m2 day d1, every 21 days cycle.; 5-fluorouracil 1000 mg/m2 day CIV 4days, repeat 21-day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (CR+PR)	In the ITT analysis(n=54), the ORR reached 77.8%: one patient (1.9%) experienced CR; 41 (75.9%), PR.	January 2009 to May 2011

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate	The disease control rate (DCR) was 90.8%.	January 2009 to May 2011

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: September 4, 2008
• First Submitted That Met QC Criteria: September 4, 2008
• First Posted (Estimate): September 5, 2008

Study Record Updates

• Last Update Posted (Estimate): December 10, 2013
• Last Update Submitted That Met QC Criteria: December 8, 2013
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: recurrent or metastatic Nasopharyngeal Neoplasms
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Fluorouracil; Sorafenib
• Other Study ID Numbers: BAY43-9006-2008003