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CompletedNCT03389295Updated Dec 16, 2019

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

A Phase 2 interventional study of Reduced Target Delineation and Radiation Doses in Nasopharyngeal Carcinoma, sponsored by Xiayun He, MD. Completed at 1 site in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2019-12-16.

Sponsored by Xiayun He, MD · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
118
Allocation
Not applicable
Ages
18 Years to 70 Years
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • Nasopharyngeal Carcinoma

Keywords

  • Nasopharyngeal Carcinoma
  • Reduced Target Delineation and Radiation Doses
  • Sequential chemoradiotherapy
03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
118 participants (actual)

Study arms

  • 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

Interventions

  • RadiationReduced 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.

    Also known as: 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)

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: up to 5 years

Secondary outcomes

  1. 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.

    Time frame: up to 5 years

  2. 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.

    Time frame: up to 5 years

  3. Overall survival

    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

  4. Distant metastasis-free survival

    The time from date of treatment until date of first documented distant metastasis, assessed up to 5 years.

    Time frame: up to 5 years

  5. 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.

    Time frame: up to 5 years

  6. Number of participants with acute toxicities

    Number of participants with acute toxicities occurred during the chemoradiotherapy according to CTCAE4.0

    Time frame: during treatment

  7. 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.

    Time frame: up to 5 years

  8. Changes of tumor volume

    Changes of tumor volume before and after induction chemotherapy

    Time frame: 2 weeks after completion of induction chemotherapy

  9. Relationship between treatment failure and dose received by target

    Relationship between treatment failure and dose received by target

    Time frame: up to 5 years

06

Study locations

1 site
  • Fudan University Shanghai Cancer Center
    Shanghai, Shanghai 200032, China
07

References and documents

Publications

  • 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. PubMed 36179488 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03389295
Lead sponsor
Xiayun He, MD
Responsible party
Xiayun He, MD (Professor, Fudan University) — Sponsor-investigator
First posted
Jan 3, 2018
Start date
Jan 2010
Primary completion
Apr 2019
Completion
Apr 2019
Last update
Dec 16, 2019

Oversight

FDA-regulated drug
No
FDA-regulated device
No
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