Trail Evaluating Carbon Ion Radiotherapy (3 GyE Per Fraction) for Locally Recurrent Nasopharyngeal Carcinoma

Shanghai Proton and Heavy Ion Center51 enrolled

Overview

The purpose of this study is to determine the maximal tolerated dose (MTD) of re-irradiation using carbon ion radiotherapy (CIRT) with the fraction size of 3 gray equivalent (GyE) in the treatment of locally recurrent nasopharyngeal cancer (NPC) and to evaluate the efficacy of such treatment at the MTD. Participants will be treated with CIRT with escalating dose regimens to evaluate the MTD in terms of acute and subacute toxicity observed within 4 months after the completion of CIRT. Once the MTD for locally recurrent NPC is determined, the MTD will be used as the recommended dose to patients fulfilling the inclusion criteria in the Phase II part of the trial.

The purpose of this study is to determine the maximal tolerated dose (MTD) of re-irradiation using carbon ion radiotherapy (CIRT) with the fraction size of 3 GyE in the treatment of locally recurrent nasopharyngeal cancer (NPC) and to evaluate the efficacy of such treatment at the MTD. Participants will be treated with CIRT with escalating dose starting from 54GyE (3GyE/daily fraction) to potentially 63GyE (3GyE/daily fraction) to evaluate the maximal tolerated dose (MTD) in terms of acute and subacute toxicity observed during and within 4 months after the completion of CIRT. The TITE-CRM method is used for the phase I dose escalating part of the trial and approximately 25 patients will be accrued. Once the MTD for locally recurrent NPC is determined, the MTD will be used as the recommended dose to patients fulfilling the inclusion criteria in the Phase II part of the trial. The Phase II part of the trial will be a single stage single arm study.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Interventions

Carbon ion radiotherapy (CIRT)RADIATION

Five dose levels (51GyE, 54GyE, 57GyE, 60GyE, 63GyE) are planned within the Phase I part. And the started dose level will be 54GyE. Daily fraction of 3 GyE will be delivered for all dose levels. After the recommended dose (RD), i.e., maximal tolerated dose, is determined or if the treatments to 63 GyE are safely delivered, the recommended dose (or 63 GyE) will be the prescribed dose in the Phase II part of the study.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Completed a definitive course of intensity-modulated photon radiation therapy (IMXT) to a total dose of ≥ 66 Gy * Recurrence diagnosed more than 12 months after the initial course of IMXT * Age ≥ 18 and \< 70 years of age * Karnofsky Performance Score ≥70 * Willing to accept adequate contraception for women with childbearing potential * Ability to understand character and individual consequences of the clinical trial * Willing to sign the written informed consent; Informed consent must be signed before the enrollment in the trial Exclusion Criteria: * Presence of distant metastasis * Technology used other than IMXT (including brachytherapy following IMXT) for the treatment of initial diagnosis of NPC * Pregnant or lactating women * Patients who have not yet recovered from acute toxicities of prior therapies * A diagnosis of malignancy other than carcinoma in situ of the cervix, basal cell carcinoma and squamous cell carcinoma of the skin within the past 5 years

Outcomes

Primary Outcomes

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (phase 1)

The primary objective of phase 1 is to identify the maximum tolerated dose which is defined as the highest dose associated with a probability of dose limiting toxicity \<=25%.

Time frame: Within 4 months after the completion of treatment

Phase 2: Overall survival (OS)

Overall survival (OS) was defined as the time frame from enrollment to the date of death from any cause.

Time frame: 2 years

Secondary Outcomes

Phase 2: Progression-free survival

Progression-free survival (PFS) was defined as the time frame from enrollment to the date of disease progression or death whichever came first.