Back to resultsReduced Target Delineation and Radiation Doses Chemoradiotherapy for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
Primary Purpose
Nasopharyngeal Carcinoma
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Reduced Target Delineation and Radiation Doses
Sponsored by
About this trial
This is an interventional treatment trial for Nasopharyngeal Carcinoma focused on measuring Nasopharyngeal Carcinoma, Reduced Target Delineation and Radiation Doses, Sequential chemoradiotherapy
Eligibility Criteria
Inclusion Criteria:
- Histopathologically proven nasopharyngeal carcinoma (WHO type 2 or 3)
- Stage Ⅲ-ⅣB disease (AJCC/UICC 2010)
- KPS more than 70
- Life expectancy of more than 6 months
- Signed written informed consent
- 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:
- Evidence of distant metastasis
- Prior chemotherapy or anti-cancer biologic therapy for any type of cancer, or prior radiotherapy to the head and neck region
- Other previous or concomitant cancer, except for in situ cervical cancer and cutaneous basal cell carcinoma
- Pregnant or breast-feeding females, or females and males of childbearing potential not taking adequate contraceptive measures
- 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
Sites / Locations
- Fudan University Shanghai Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Reduced Target Delineation and Radiation Doses
Arm Description
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.
Outcomes
Primary Outcome Measures
Progression-free survival
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
Local recurrence-free survival
The time from date of treatment until date of first documented disease recurrence at a local site, assessed up to 5 years.
Regional recurrence-free survival
The time from date of treatment until date of first documented disease recurrence at a regional site, assessed up to 5 years.
Overall survival
The time from date of treatment until date of death due to any cause, assessed up to 5 years.
Distant metastasis-free survival
The time from date of treatment until date of first documented distant metastasis, assessed up to 5 years.
Locoregional failure patterns
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.
Number of participants with acute toxicities
Number of participants with acute toxicities occurred during the chemoradiotherapy according to CTCAE4.0
Number of participants with late toxicities
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.
Changes of tumor volume
Changes of tumor volume before and after induction chemotherapy
Relationship between treatment failure and dose received by target
Relationship between treatment failure and dose received by target
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03389295
Brief Title
Reduced Target Delineation and Radiation Doses Chemoradiotherapy for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
Official Title
Sequential Chemoradiotherapy With Reduced Target Delineation and Radiation Doses During Radiotherapy for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
January 2010 (Actual)
Primary Completion Date
April 2019 (Actual)
Study Completion Date
April 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Xiayun He, MD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nasopharyngeal Carcinoma
Keywords
Nasopharyngeal Carcinoma, Reduced Target Delineation and Radiation Doses, Sequential chemoradiotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
118 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Reduced Target Delineation and Radiation Doses
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Reduced Target Delineation and Radiation Doses
Other Intervention Name(s)
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)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free survival
Description
The time from date of treatment until date of first documented disease progression or death from any cause, assessed up to 5 years.
Time Frame
up to 5 years
Secondary Outcome Measure Information:
Title
Local recurrence-free survival
Description
The time from date of treatment until date of first documented disease recurrence at a local site, assessed up to 5 years.
Time Frame
up to 5 years
Title
Regional recurrence-free survival
Description
The time from date of treatment until date of first documented disease recurrence at a regional site, assessed up to 5 years.
Time Frame
up to 5 years
Title
Overall survival
Description
The time from date of treatment until date of death due to any cause, assessed up to 5 years.
Time Frame
up to 5 years
Title
Distant metastasis-free survival
Description
The time from date of treatment until date of first documented distant metastasis, assessed up to 5 years.
Time Frame
up to 5 years
Title
Locoregional failure patterns
Description
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.
Time Frame
up to 5 years
Title
Number of participants with acute toxicities
Description
Number of participants with acute toxicities occurred during the chemoradiotherapy according to CTCAE4.0
Time Frame
during treatment
Title
Number of participants with late toxicities
Description
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.
Time Frame
up to 5 years
Title
Changes of tumor volume
Description
Changes of tumor volume before and after induction chemotherapy
Time Frame
2 weeks after completion of induction chemotherapy
Title
Relationship between treatment failure and dose received by target
Description
Relationship between treatment failure and dose received by target
Time Frame
up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histopathologically proven nasopharyngeal carcinoma (WHO type 2 or 3)
Stage Ⅲ-ⅣB disease (AJCC/UICC 2010)
KPS more than 70
Life expectancy of more than 6 months
Signed written informed consent
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:
Evidence of distant metastasis
Prior chemotherapy or anti-cancer biologic therapy for any type of cancer, or prior radiotherapy to the head and neck region
Other previous or concomitant cancer, except for in situ cervical cancer and cutaneous basal cell carcinoma
Pregnant or breast-feeding females, or females and males of childbearing potential not taking adequate contraceptive measures
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
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
36179488
Citation
Xue F, Ou D, Ou X, Zhou X, Hu C, He X. Long-term results of the phase II dose and volume de-escalation trial for locoregionally advanced nasopharyngeal carcinoma. Oral Oncol. 2022 Nov;134:106139. doi: 10.1016/j.oraloncology.2022.106139. Epub 2022 Sep 27.
Results Reference
derived
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Reduced Target Delineation and Radiation Doses Chemoradiotherapy for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma
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