Nasopharyngeal Cancinoma (NPC)
Conditions
Keywords
Proton, Photon, Carbon ion, Phase 3 Trial, Locally Advanced NPC
Brief summary
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
RADIATIONIntensity-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.
RADIATIONIntensity-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.
RADIATIONIntensity-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.
DRUGConcurrent chemotherapy
Concurrent chemotherapy will be administered on a weekly basis.
DRUGInduction chemotherapy
Cisplatin-based induction chemotherapy will be administered every three weekly.
Sponsors
Lin Kong, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | 3 years | Progression-free survival (PFS) defined as the time interval from randomization to death or disease progression whichever comes first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Assessment of Cancer Therapy | 3 years | Patient-reported outcome, Functional Assessment of Cancer Therapy (FACT). |
| Xerostomia Questionnaire | 3 years | Patient-reported outcome, Xerostomia Questionnaire (XQ). |
| MD Anderson Dysphagia Inventory | 3 years | Patient-reported outcome, MD Anderson Dysphagia Inventory (MADI). |
| Overall survival | 3 years | Overall survival (OS) is defined as the time interval from randomization to death. |
| Prevalence of grade ≥3 late toxicities | 3 years | Prevalence of grade ≥3 late toxicities graded by CTCAE v5. |
| Distant metastasis-free survival | 3 years | Distant metastasis-free survival (DMFS) is defined as the time interval from randomization to death or distant metastasis whichever comes first. |
| Prevalence of grade ≥2 acute toxicities | 3 years | Prevalence of grade ≥2 acute toxicities graded by CTCAE v5. |
| Prevalence of grade ≥3 acute toxicities | 3 years | Prevalence of grade ≥3 acute toxicities graded by CTCAE v5. |
| Prevalence of grade ≥2 late toxicities | 3 years | Prevalence of grade ≥2 late toxicities graded by CTCAE v5. |
| Locoregional progression-free survival | 3 years | Locoregional progression-free survival (LRPFS) is defined as the time interval from randomization to death or locoregional failure whichever comes first. |
Countries
China
Contacts
Primary ContactLin Kong
Backup ContactJiyi Hu
Outcome results
None listed