Reduced Target Delineation Chemoradiotherapy for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

• ClinicalTrials.gov Identifier: NCT03389295
• Recruitment Status: Recruiting
• First Posted: January 3, 2018
• Last Update Posted: January 3, 2018
• Sponsor: Xiayun He, MD
• Information provided by (Responsible Party): Xiayun He, MD, Fudan University

Study Description

Brief Summary:

To determine the efficacy and safety of sequential chemoradiotherapy with regimen of docetaxel, cisplatin and fluorouracil and reduced target delineation radiotherapy for patients with locoregionally advanced nasopharyngeal carcinoma

Condition or disease	Intervention/treatment	Phase
Nasopharyngeal Carcinoma	Radiation: Reduced Target Delineation	Phase 2

Detailed Description:

Although concurrent chemoradiation is the standard treatment modality for locally advanced nasopharyngeal carcinoma (NPC), high incidences of distant metastases and severe treatment related toxicities have become an obstacle to be overcome. Besides, a common problem in locally advanced NPC is the narrow gap between the tumor and critical normal structures, which makes dose optimization difficult. Considering that significant tumor shrinkage may occur during induction chemotherapy, and incidences of distant metastases may be reduced by adjuvant chemotherapy, this study was designed to explore the efficacy and safety of sequential chemoradiotherapy with regimen of docetaxel, cisplatin and fluorouracil and reduced target delineation radiotherapy for patients with locoregionally advanced NPC.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 180 participants
• Intervention Model: Single Group Assignment
• Intervention Model Description: Drug: TPF regimen comprised docetaxel (60 mg/m2/day, day 1), cisplatin (25 mg/m2/day, days 1-3), and 5-fluorouracil (500 mg/m2/day with a 120-h infusion) Radiotherapy：Reduced Target Delineation
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Sequential Chemoradiotherapy With Reduced Target Delineation During Radiotherapy for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
• Actual Study Start Date: October 2014
• Estimated Primary Completion Date: October 2020
• Estimated Study Completion Date: October 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: Reduced Target Delineation Chemoradiotherapy; All patients were assigned to receive induction chemotherapy (IC) followed by IMRT with adjuvant chemotherapy (AC). IMRT was administered 2 weeks after IC, and AC was administered 1 month after IMRT. IC or AC (TPF regimen) comprised docetaxel (60 mg/m2/day, day 1), cisplatin (25 mg/m2/day, days 1-3), and 5-fluorouracil (500 mg/m2/day with a 120-h infusion) administered once every 3 weeks for two cycles. During radiotherapy, involved retropharyngeal lymph nodes and intracavity lesions of the primary tumor were delineated according to the post-IC volume, whereas the remainder of the involved tissues (eg, pterygopalatine fossa) of the primary tumor were delineated according to the pre-IC volume of the primary tumor as shown by MRI. Post-IC volumes of involved neck lymph nodes were used for delineation.

Radiation: Reduced Target Delineation; The target volumes were delineated according to the treatment protocol defined as follows: the GTV of the primary tumor (GTV-P) included retropharyngeal lymph nodes, considering the common phenomena of integration, and the rest involved lymph nodes that were defined as GTV-N. For the GTV-P, involved retropharyngeal lymph nodes and intracavity lesions were delineated according to the post-IC volume, whereas the remainder of the involved tissues (eg, pterygopalatine fossa) were delineated according to the pre-IC volume of the primary lesion as shown by MRI. Post-IC volumes of involved neck lymph nodes were used for GTV-N delineation.; Other Name: Drug: TPF regimen comprised docetaxel (60 mg/m2/day, day 1), cisplatin (25 mg/m2/day, days 1-3), and 5-fluorouracil (500 mg/m2/day with a 120-h infusion)

Outcome Measures

Primary Outcome Measures :

1. Progression-free survival [ Time Frame: up to 3 years ]
   The time from date of treatment until date of first documented disease progression or death from any cause, assessed up to 3 years.

Secondary Outcome Measures :

1. Overall survival [ Time Frame: up to 3 years ]
   The time from date of treatment until date of death due to any cause, assessed up to 3 years.
2. Locoregional recurrence-free survival [ Time Frame: up to 3 years ]
   The time from date of treatment until date of first documented disease recurrence at a locoregional site, assessed up to 3 years.
3. Distant metastasis-free survival [ Time Frame: up to 3 years ]
   The time from date of treatment until date of first documented distant metastasis, assessed up to 3 years.
4. Number of participants with hematologic toxicity events [ Time Frame: 1, 2 , 3 weeks post-dose ]
   Number of participants with hematologic toxicity events occurred during two cycles of induction and adjuvant chemotherapy according to CTCAE v4.
5. Number of participants with acute toxicities [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 6 weeks ]
   Number of participants with acute toxicities (hematologic toxicity events, oral mucositis, acne-like rash) occurred during the radiotherapy
6. Number of participants with late toxicities [ Time Frame: up to 3 years ]
   Number of participants with late toxicities (hematologic toxicity events, dysphagia, acne-like rash or neurological toxicities) occurred from 3 months after completion of radiotherapy to last follow-up visit according to CTCAE v4.0
7. Changes of tumor volume [ Time Frame: 2 weeks after completion of induction chemotherapy ]
   Changes of tumor volume before and after induction chemotherapy
8. Relationship between treatment failure and dose received by target [ Time Frame: up to 3 years ]
   Relationship between treatment failure and dose received by target

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Histopathologically proven nasopharyngeal carcinoma (WHO type 2 or 3)
2. Stage Ⅲ-ⅣB disease (AJCC/UICC 2010)
3. ECOG performance status of 0-1
4. Life expectancy of more than 6 months
5. Signed written informed consent
6. Adequate organ function including the following:

Absolute neutrophil count (ANC) >= 1.5 * 109/l Platelets count >= 100 * 109/l Hemoglobin >= 10 g/dl AST and ALT <= 2.5 times institutional upper limit of normal (ULN) Total bilirubin <= 1.5 times institutional ULN Creatinine clearance >= 50 ml/min Serum creatine <= 1 times ULN

Exclusion Criteria:

1. Evidence of distant metastasis
2. Prior chemotherapy or anti-cancer biologic therapy for any type of cancer, or prior radiotherapy to the head and neck region
3. Other previous or concomitant cancer, except for in situ cervical cancer and cutaneous basal cell carcinoma
4. Pregnant or breast-feeding females, or females and males of childbearing potential not taking adequate contraceptive measures
5. Presence of an uncontrolled concomitant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia

Contacts and Locations

Contacts

Contact: Xiayun He, MD; +86-18017312167; hexiayun1962@163.com

Locations

China, Shanghai

Fudan University Shanghai Cancer Center; Recruiting

Shanghai, Shanghai, China, 200032

Contact: Xiayun He, MD +86-18017312167 hexiayun1962@163.com

Contact: Fen Xue, MD +86-18505123563 xuefen1992@126.com

Sponsors and Collaborators

Xiayun He, MD

More Information

• Responsible Party: Xiayun He, MD, Professor, Fudan University
• ClinicalTrials.gov Identifier: NCT03389295 History of Changes
• Other Study ID Numbers: TPF-Shanghai
• First Posted: January 3, 2018
• Last Update Posted: January 3, 2018
• Last Verified: December 2017

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xiayun He, MD, Fudan University:

Nasopharyngeal Carcinoma; Reduced Target Delineation; Sequential chemoradiotherapy

Additional relevant MeSH terms:

Carcinoma; Nasopharyngeal Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Cisplatin; Docetaxel; Fluorouracil; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Antimetabolites, Antineoplastic; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs