Reduced Target Delineation and Radiation Doses Chemoradiotherapy for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

• ClinicalTrials.gov Identifier: NCT03389295
• Recruitment Status: Completed
• First Posted: January 3, 2018
• Last Update Posted: December 16, 2019
• 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 and radiation doses IMRT for patients with locoregionally advanced nasopharyngeal carcinoma

Condition or disease	Intervention/treatment	Phase
Nasopharyngeal Carcinoma	Radiation: Reduced Target Delineation and Radiation Doses	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 and radiation doses IMRT for patients with locoregionally advanced NPC.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 118 participants
• Allocation: N/A
• 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 and Radiation Doses During Radiotherapy for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
• Actual Study Start Date: January 2010
• Actual Primary Completion Date: April 2019
• Actual Study Completion Date: April 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: Reduced Target Delineation and Radiation Doses; 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. The prescribed dose was 66 Gy to tumors above the slices of skull base or below the orapharynx with less than 5 mm retropharyngeal lymph nodes, or 70.4 Gy to tumors in other slices.

Radiation: Reduced Target Delineation and Radiation Doses; 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. The prescribed dose was 66 Gy to tumors above the slices of skull base or below the orapharynx with less than 5 mm retropharyngeal lymph nodes, or 70.4 Gy to tumors in other slices.; 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 5 years ]
   The time from date of treatment until date of first documented disease progression or death from any cause, assessed up to 5 years.

Secondary Outcome Measures :

1. Local recurrence-free survival [ Time Frame: up to 5 years ]
   The time from date of treatment until date of first documented disease recurrence at a local site, assessed up to 5 years.
2. Regional recurrence-free survival [ Time Frame: up to 5 years ]
   The time from date of treatment until date of first documented disease recurrence at a regional site, assessed up to 5 years.
3. Overall survival [ Time Frame: up to 5 years ]
   The time from date of treatment until date of death due to any cause, assessed up to 5 years.
4. Distant metastasis-free survival [ Time Frame: up to 5 years ]
   The time from date of treatment until date of first documented distant metastasis, assessed up to 5 years.
5. Locoregional failure patterns [ Time Frame: up to 5 years ]
   The failures were categorized as occurring inside or outside the high dose target volume, depending on the location of Vrecur: "in field" if 95% of Vrecur was within the 95% isodose; "marginal" if 20% to 95% of Vrecur was within the 95% isodose, or "outside" if less than 20% of Vrecur was inside the 95% isodose.
6. Number of participants with acute toxicities [ Time Frame: during treatment ]
   Number of participants with acute toxicities occurred during the chemoradiotherapy according to CTCAE4.0
7. Number of participants with late toxicities [ Time Frame: up to 5 years ]
   Number of participants with late toxicities occurred from 3 months after completion of radiotherapy to last follow-up visit according to Radiation Therapy Oncology Group radiation morbidity scoring criteria.
8. Changes of tumor volume [ Time Frame: 2 weeks after completion of induction chemotherapy ]
   Changes of tumor volume before and after induction chemotherapy
9. Relationship between treatment failure and dose received by target [ Time Frame: up to 5 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. KPS more than 70
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

Locations

China, Shanghai

Fudan University Shanghai Cancer Center

Shanghai, Shanghai, China, 200032

Sponsors and Collaborators

Xiayun He, MD

More Information

• Responsible Party: Xiayun He, MD, Professor, Fudan University
• ClinicalTrials.gov Identifier: NCT03389295
• Other Study ID Numbers: TPF-Shanghai
• First Posted: January 3, 2018
• Last Update Posted: December 16, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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 and Radiation Doses; 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