Phase 3 Trial Comparing IMRT or IMPT Plus CIRT for Patients With NPC

Overview

The goal of this phase 3 non-inferiority trial is to compare the efficacy and toxicity of proton or photon radiation therapy plus carbon ion radiation therapy for newly diagnosed nasopharyngeal carcinoma. The main question it aims to answer is that if proton radiation therapy plus carbon ion radiation therapy is non-inferior to photon radiation therapy plus carbon ion radiation therapy in terms of therapeutic efficacy. Participants will be randomized to receive either proton radiation therapy (arm 1) or photon radiation therapy (arm 2), in addition to carbon ion radiation therapy (for both arms).

Detailed description

This is a phase 3 randomized non-inferiority trial. The primary objective of the trial is to compare progression-free survival between proton plus carbon ion radiation therapy (arm 1) and photon plus carbon ion radiation therapy (arm 2) for patients with newly diagnosed nasopharyngeal carcinoma (NPC). The secondary objectives includes overall survival, locoregional progression-free survival, distant metastasis-free survival, physician-graded toxicities according to the CTCAE, and patients-reported outcomes. This study adopts a web-based central randomization system. The randomization method uses minimization, with two balancing factors: Stage (AJCC Staging System, 9th edition): Stage I vs. Stages II/III; Response to induction chemotherapy: No induction chemotherapy vs. sensitive (CR + PR) vs. resistant (SD + PD). Eligible patients will be randomized in a 1:1 ratio into either the experimental group or the control group. This is an open-label study, meaning both patients and investigators are aware of the treatment allocation.

Participants randomized to arm 1 will receive proton therapy with a dose of 56 GyRBE in 28 fractions, in addition to a boost delivered using carbon ion radiation therapy with a dose of 17.5 GyRBE in 5 fractions. Participants randomized to arm 2 will receive photon therapy with a dose of 56 Gy in 28 fractions, plus carbon ion radiation therapy with a dose of 17.5 GyRBE in 5 fractions. The treatment response will be evaluated according to the RECIST criteria.

Induction chemotherapy and concurrent chemotherapy will be prescribed according to disease stage.

Interventions

• Radiation Intensity-modulated proton radiation therapy
  Intensity-modulated proton therapy, will be delivered to the high risk area with a dose of 56 GyRBE in 28 fractions, and if applicable, to the low risk area with a dose of 50.4 GyRBE in 28 fractions.
• Radiation Intensity-modulated photon radiation therapy
  Intensity-modulated photon therapy, will be delivered to the high risk area with a dose of 56 Gy in 28 fractions, and if applicable, to the low risk area with a dose of 50.4 Gy in 28 fractions.
• Radiation Intensity-modulated carbon ion radiation therapy
  Intensity-modulated carbon ion radiation therapy will be delivered as a boost with a dose of 17.5 GyRBE in 5 fractions to gross tumor.
• Drug Concurrent chemotherapy
  Concurrent chemotherapy will be administered on a weekly basis.
• Drug Induction chemotherapy
  Cisplatin-based induction chemotherapy will be administered every three weekly.

Primary outcome measures

• Progression-free survival [Time frame: 3 years]

Secondary outcome measures (10)

• Overall survival [Time frame: 3 years]
• Locoregional progression-free survival [Time frame: 3 years]
• Distant metastasis-free survival [Time frame: 3 years]
• Prevalence of grade ≥2 acute toxicities [Time frame: 3 years]
• Prevalence of grade ≥3 acute toxicities [Time frame: 3 years]
• Prevalence of grade ≥2 late toxicities [Time frame: 3 years]
• Prevalence of grade ≥3 late toxicities [Time frame: 3 years]
• Functional Assessment of Cancer Therapy [Time frame: 3 years]
• Xerostomia Questionnaire [Time frame: 3 years]
• MD Anderson Dysphagia Inventory [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Willingness to sign the written informed consent.
• Pathologically confirmed Nasopharyngeal carcinoma.
• Patients with any stage of disease except distant metastasis.
• Age: ≥ 18 and ≤ 70 years old.
• Eastern Cooperative Oncology Group score: 0-1.
• Adequate laboratory test results.
• Willingness to accept adequate contraception.

Exclusion criteria

• Presence of distant metastasis.
• Previous radiotherapy to head and neck region.
• Previous surgery (except for biopsy) for the primary lesion or cervical lymph nodes.
• History of malignant tumor within the past 5 years.
• Presence of multiple primary tumors.
• Presence of diseases that may interfere with the evaluation of study endpoints.
• Presence of severe major organ dysfunction.
• Mental illness that may affect the understanding of informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Proton and Heavy Ion Center — Shanghai

Publications

• Hu J, Huang Q, Gao J, Hu W, Yang J, Guan X, Qiu X, Zhang W, Kong L, Lu JJ. Mixed Photon and Carbon-Ion Beam Radiotherapy in the Management of Non-Metastatic Nasopharyngeal Carcinoma. Front Oncol. 2021 Jul 23;11:653050. doi: 10.3389/fonc.2021.653050. eCollection 2021. PMID 34367954
• Li X, Kitpanit S, Lee A, Mah D, Sine K, Sherman EJ, Dunn LA, Michel LS, Fetten J, Zakeri K, Yu Y, Chen L, Kang JJ, Gelblum DY, McBride SM, Tsai CJ, Riaz N, Lee NY. Toxicity Profiles and Survival Outcomes Among Patients With Nonmetastatic Nasopharyngeal Carcinoma Treated With Intensity-Modulated Proton Therapy vs Intensity-Modulated Radiation Therapy. JAMA Netw Open. 2021 Jun 1;4(6):e2113205. doi: PMID 34143193
• Lewis GD, Holliday EB, Kocak-Uzel E, Hernandez M, Garden AS, Rosenthal DI, Frank SJ. Intensity-modulated proton therapy for nasopharyngeal carcinoma: Decreased radiation dose to normal structures and encouraging clinical outcomes. Head Neck. 2016 Apr;38 Suppl 1:E1886-95. doi: 10.1002/hed.24341. Epub 2015 Dec 26. PMID 26705956
• Vai A, Molinelli S, Rossi E, Iacovelli NA, Magro G, Cavallo A, Pignoli E, Rancati T, Mirandola A, Russo S, Ingargiola R, Vischioni B, Bonora M, Ronchi S, Ciocca M, Orlandi E. Proton Radiation Therapy for Nasopharyngeal Cancer Patients: Dosimetric and NTCP Evaluation Supporting Clinical Decision. Cancers (Basel). 2022 Feb 22;14(5):1109. doi: 10.3390/cancers14051109. PMID 35267415
• Minatogawa H, Yasuda K, Dekura Y, Takao S, Matsuura T, Yoshimura T, Suzuki R, Yokota I, Fujima N, Onimaru R, Shimizu S, Aoyama H, Shirato H. Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas. J Appl Clin Med Phys. 2021 Jan;22(1):174-183. doi: 10.1002/acm2.13128. Epub 2020 Dec 18. PMID 33338323
• Lin YH, Cheng JY, Huang BS, Luo SD, Lin WC, Chou SY, Juang PJ, Li SH, Huang EY, Wang YM. Significant Reduction in Vertebral Artery Dose by Intensity Modulated Proton Therapy: A Pilot Study for Nasopharyngeal Carcinoma. J Pers Med. 2021 Aug 22;11(8):822. doi: 10.3390/jpm11080822. PMID 34442466
• Taheri-Kadkhoda Z, Bjork-Eriksson T, Nill S, Wilkens JJ, Oelfke U, Johansson KA, Huber PE, Munter MW. Intensity-modulated radiotherapy of nasopharyngeal carcinoma: a comparative treatment planning study of photons and protons. Radiat Oncol. 2008 Jan 24;3:4. doi: 10.1186/1748-717X-3-4. PMID 18218078
• Widesott L, Pierelli A, Fiorino C, Dell'oca I, Broggi S, Cattaneo GM, Di Muzio N, Fazio F, Calandrino R, Schwarz M. Intensity-modulated proton therapy versus helical tomotherapy in nasopharynx cancer: planning comparison and NTCP evaluation. Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):589-96. doi: 10.1016/j.ijrobp.2008.05.065. PMID 18793962

Identifiers

NCT: NCT06846450 · SPHIC-TR-HNCNS-2024-70

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗