Optimization of Cervical Nodal CTV for Early and Medium Stage NPC

NCT ID: NCT05145660

Last Updated: 2022-09-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 414 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2027-08-31

Brief Summary

Current radiotherapy guidelines and consensus statements uniformly recommend elective region irradiation (ERI) as the standard strategy for nasopharyngeal carcinoma (NPC). However, given the scarcity of skip-metastasis, the improved assessment accuracy of nodal involvement, and the striking advancements in chemotherapy for NPC, a one-fits-all delineation scheme for clinical target volumes for the nodal region (CTVn) may not be appropriate anymore, and modifications of the CTVn delineation strategy may be warranted. Involved site irradiation (ISI) covering merely the initially involved nodal site and potential extranodal extension has been confirmed to be as effective as ERI with decreased radiation-related toxicities in some malignancies, but has not yet been investigated in NPC. This study aims to compare the regional control, survival outcomes, radiation-related toxicities, and quality of life (QoL) of ISI with conventional ERI in NPC patients with a limited nodal burden.

Detailed Description

ISRT-NPC is a prospective, multicenter, open-label, noninferiority, phase III randomized controlled trial. A total of 488 patients will be randomly assigned in a 1:1 ratio to receive ISI or ERI. Randomization will be stratified by institution and N stage. Generally, in the ISI group, the high-risk CTV1 (dose: 60 Gy) includes a 1-cm expansion of the positive LN as well as the VIIa and the retrostyloid space above the bilateral transverse process of the atlantoaxial spine (C1), regardless of N status. The low-risk CTV2 (Dose: 50 Gy) covers the cervical nodal region with a 3-cm caudal expansion below the transverse process of C1 for N0 disease and a 3-cm expansion below the positive LN for positive LNs (at least covering the level II).

Conditions

Nasopharyngeal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Involved site irradiation

High-risk CTV1 : GTVnx plus a 10-mm margin to encompass the microscopic extension of the gross tumor, the whole nasopharynx, the high-risk structures recommended for CTVp2 by the contouring consensus* (such as parapharyngeal space, skull base, pterygopalatine fossa and the inferior part of the nasal cavity and maxillary sinus), the VIIa, and the retrostyloid space above the bilateral transverse process of C1.

Low-risk CTV2:

N0/positive RPLN only: Bilateral cervical nodal region with the 3-cm caudal expansion below transverse process of C1, and at least covering the level II.

N1-2 (positive cervical LNs): Ipilateral cervical nodal region with the 3-cm expansion below the positive LN (GTVnd), and at least covering the level II; contralateral cervical nodal region with the 3-cm caudal expansion below the transverse process of C1, and at least covering the level II.

Suspicious LN: 1-cm expansion below the suspicious LN (GTVnd-suspicious)

Group Type: EXPERIMENTAL

intensity-modulated radiotherapy (IMRT) with reduced-volume

Intervention Type: RADIATION

PGTVnx: 69.9Gy/2.12Gy/33f GTVrpn: 69.9Gy/2.12Gy/33f GTVnd: 69.9Gy/2.12Gy/33f GTVnd-suspicious: 60.06Gy/1.82Gy/33f PTV1: 60.06Gy/1.82Gy/33f PTV2: 50.96Gy/1.82Gy/28f

Chemotherapy

Intervention Type: DRUG

Concurrent cisplatin (100 mg/m², d1-3, Q3w, maximum to three cycles); The application of induction chemotherapy and consolidation chemotherapy is dependent on the physician's discretion.

Elective region irradiation

High-risk CTV1 : GTVnx plus a 10-mm margin to encompass the microscopic extension of the gross tumor, the whole nasopharynx, the high-risk structures recommended for CTVp2 by the contouring consensus* (such as parapharyngeal space, skull base, pterygopalatine fossa and the inferior part of the nasal cavity and maxillary sinus), the VIIa, and the retrostyloid space above the bilateral transverse process of C1.

Low-risk CTV2:

N0/positive RPLN only: Bilateral level III + Va N1-2 (positive cervical LNs): At least one subsequent level below CTV1

Group Type: ACTIVE_COMPARATOR

intensity-modulated radiotherapy (IMRT) with reduced-volume

Intervention Type: RADIATION

PGTVnx: 69.9Gy/2.12Gy/33f GTVrpn: 69.9Gy/2.12Gy/33f GTVnd: 69.9Gy/2.12Gy/33f GTVnd-suspicious: 60.06Gy/1.82Gy/33f PTV1: 60.06Gy/1.82Gy/33f PTV2: 50.96Gy/1.82Gy/28f

Chemotherapy

Intervention Type: DRUG

Concurrent cisplatin (100 mg/m², d1-3, Q3w, maximum to three cycles); The application of induction chemotherapy and consolidation chemotherapy is dependent on the physician's discretion.

Interventions

intensity-modulated radiotherapy (IMRT) with reduced-volume

PGTVnx: 69.9Gy/2.12Gy/33f GTVrpn: 69.9Gy/2.12Gy/33f GTVnd: 69.9Gy/2.12Gy/33f GTVnd-suspicious: 60.06Gy/1.82Gy/33f PTV1: 60.06Gy/1.82Gy/33f PTV2: 50.96Gy/1.82Gy/28f

Intervention Type: RADIATION

Chemotherapy

Concurrent cisplatin (100 mg/m², d1-3, Q3w, maximum to three cycles); The application of induction chemotherapy and consolidation chemotherapy is dependent on the physician's discretion.

Intervention Type: DRUG

Other Intervention Names

intensity-modulated radiotherapy

Eligibility Criteria

Inclusion Criteria

1. Age between 18 and 75 years;

2. Karnofsky performance status (KPS) score ≥ 70;

3. Pathologically confirmed World Health Organization (WHO) type II-III NPC;

4. TNM stage I-III (T1-3N0-2M0) according to the 8th American Joint Committee on Cancer / Union for International Cancer Control (AJCC/UICC) staging system with a maximum diameter (MAD) of cervical involved LNs ≤ 3 cm, namely LB-LN;

5. Available baseline nasopharynx and neck computed tomography (CT) or magnetic resonance imaging (MRI) (strongly advocated) data (including functional MRI sequences) and measurable tumor lesions;

6. All procedures for defining the tumor burden completed within 4 weeks of registration;

7. Survival expectancy of at least 6 months;

8. Normal marrow and organ function: hemoglobin ≥ 120 g/L, WBCs ≥ 4 × 109 /L, platelets ≥ 100 × 109 /L; liver and kidney function-related indicators within 1.25*the normal upper limit;

9. Patient willingness to comply with the protocol;

10. Patient willingness and ability to provide an informed consent form.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Jun-Lin Yi, MD

UNKNOWN

Sponsor Role: lead

Responsible Party

Jun-Lin Yi, MD

Radiotherapy director

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Junlin Yi

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Medical Sciences

Locations

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Junlin Yi, doctor

Role: CONTACT

yijunlin1969@163.com

13661217998

Facility Contacts

Junlin Yi, MD

Role: primary

yijunlin1969@163.com

861087788504

References

Liu Y, Han Y, Liu F, Hu D, Chen Z, Wang P, Li J, Qin J, Jin F, Li Y, Wang J, Yi J. Involved site radiation therapy in stage I-III nasopharyngeal carcinoma with limited lymph node burden (ISRT-NPC) or elective region irradiation: a study protocol for a multicenter non-inferiority randomized controlled phase III clinical trial. BMC Cancer. 2023 Aug 3;23(1):724. doi: 10.1186/s12885-023-11212-7.

Reference Type: DERIVED

PMID: 37537541 (View on PubMed)

Other Identifiers

NCC-2021C-257

Identifier Type: -

Identifier Source: org_study_id