Clinical trial NCT04143984: Carbon-Ion Radiotherapy Plus Camrelizumab for Locally Recurrent Nasopharyngeal Carcinoma
Official title: A Phase 2 Randomized Clinical Trial to Examine the Efficacy of Carbon-Ion Radiotherapy Plus Camrelizumab As Salvage Treatment for Locally Recurrent Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Lead sponsor: Shanghai Proton and Heavy Ion Center
Sponsor class: OTHER
First posted: 2019-10-30
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to examine the role of camrezlizumab in addition to carbon-ion radiotherapy (CIRT) for patients with locally recurrent nasopharyngeal carcinoma. According to the plan, a total of 146 patients will be recruited and randomized into: 1) CIRT alone group (control group); 2) CIRT plus camrelizumab group (experimental group).

Detailed description: Treatment for locally recurrent nasopharyngeal carcinoma (LR-NPC) is challenging. Carbon-ion radiotherapy appeared to be an effective treatment for this group of patients, and has substantially improved the 2-year overall survival (OS) to approximately 85%, compared to photon-based intensity-modulated radiotherapy. However, a group of the patients may still develop disease progression after CIRT, and the 2-year progression-free survival (PFS) was approximately 45%-50%. Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been demonstrated that it is effective in the recurrent/metastatic nasopharyngeal carcinoma; however, the role of camrelizumab in concurrence with radiotherapy, especially CIRT, for LR-NPC is not clear. The purpose of this phase 2 clinical trial is to compare the efficacy of CIRT plus camrelizumab and CIRT alone in the treatment of LR-NPC. Eligible participants will be randomized (1:1) to 1) CIRT alone group (control group); 2) CIRT plus camrelizumab group (experimental group). The primary endpoint is progression-free survival. Secondary endpoints include overall survival (OS), local progression-free survival (LPFS), regional progression-free survival (RPFS), and distant metastasis-free survival (DMFS) and toxicities. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.

Eligibility criteria: Inclusion Criteria:

* Completed a definitive course of intensity-modulated photon radiation therapy (IMRT) to a total dose of ≥ 66 Gy
* Recurrence at nasopharynx diagnosed more than 6 months after the initial course of IMRT
* Patients with neck lymphadenopathy should receive neck dissection before randomization
* With measurable lesion on contrast MR scan
* Age ≥ 18 and \< 70 years of age
* ECOG score: 0-1
* Leucocyte count ≥ 4000/µL, neutrocyte count ≥ 2000/µL, platelet count ≥ 100000/µL, hemoglobin ≥ 90g/L
* Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) \< 1.5×upper limit of normal (ULN), alkaline phosphatase \< 2.5×ULN, bilirubin ≤ ULN, serum creatinine ≤ ULN, creatinine clearance ≥ 60ml/min
* Willing to accept adequate contraception
* Ability to understand the nature of the clinical trial and sign the written informed consent

Exclusion Criteria:

* Presence of distant metastasis
* Previously received radioactive particle implantation
* Prior malignancy within 5 years before randomization, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer
* Patients who received local (such as surgery and cryotherapy) or systemic treatment, except for induction chemotherapy after diagnosis of recurrence
* With uncontrolled active infection
* With pneumonia
* With autoimmune disease
* With a known history of testing positive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
* Hepatitis B virus (HBV) DNA ≥ 500IU/mL for patients with positive HBV surface antigen, positive hepatitis C virus RNA for patients with positive HCV antigen
* Previously treated by immune checkpoint inhibitors
* Medical conditions requiring treatment of antibiotics and/or corticosteroid
* Treated with ≥ 5 days antibiotics one month before start of immunotherapy
* With known allergy to any of the study drugs
* Pregnant or lactating women
* Any severe intercurrent disease that may interfere with the current study

Primary outcomes:
measure: Progression-free survival
timeFrame: 2-year
Secondary outcomes:
measure: Overall survival
timeFrame: 2-year
measure: Local progression-free survival
timeFrame: 2-year
measure: Regional progression-free survival
timeFrame: 2-year
measure: Distant metastasis-free survival
timeFrame: 2-year
measure: Number of participants with adverse events
timeFrame: 2-year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Proton and Heavy Ion Center
state: Shanghai
Study officials:
affiliation: Shanghai Proton and Heavy Ion Center
name: Jiade J Lu, MD
role: PRINCIPAL_INVESTIGATOR
References: