Clinical trial NCT04534855: A Phase II Clinical Study of Treprilimab in the Treatment of Recurrent Nasopharyngeal Carcinoma After Re-irradiation
Official title: A Phase II Single Arm Clinical Study of Treprilimab in the Treatment of Local Recurrent/Residual Nasopharyngeal Carcinoma After Re-irradiation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma
Keywords: Treprilimab,recurrent/residual NPC
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2020-09-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To establish the antitumor activity and safety of the anti-programmed death 1 receptor monoclonal antibody, Treprilimab, in patients with local recurrent/residual nasopharyngeal carcinoma after re-irradiation.Patients with local recurrent/residual NPC after re-irradiation were treated with Treprilimab until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity.The sample size of this study was estimated on the assumption that response rates (RRs) to Treprilimab should be around 25%,based on a report that was available at the time this study was planned.Furthermore, the RR to noncytotoxic, experimental agents such as pazopanib and cetuximab in similarly pretreated patient cohorts was approximately 5% to 10%. This study's design was based on the modiﬁed Simon two-stage optimal design (α=0.05，β=0.2,n1=2/22,n2=7/40). If two responses were observed during the ﬁrst stage, enrollment was continued until a total of 40 patients was reached.

Detailed description: To establish the antitumor activity and safety of the anti-programmed death 1 receptor monoclonal antibody, Treprilimab, in patients with local recurrent/residual nasopharyngeal carcinoma after re-irradiation.Patients with local recurrent/residual NPC after re-irradiation were treated with Treprilimab until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) and secondary end points included survival and toxicity.The sample size of this study was estimated on the assumption that response rates (RRs) to Treprilimab should be around 25%,based on a report that was available at the time this study was planned.Furthermore, the RR to noncytotoxic, experimental agents such as pazopanib and cetuximab in similarly pretreated patient cohorts was approximately 5% to 10%. This study's design was based on the modiﬁed Simon two-stage optimal design (α=0.05，β=0.2,n1=2/22,n2=7/40). If two responses were observed during the ﬁrst stage, enrollment was continued until a total of 40 patients was reached. The target lesions had to be measurable by the Response Evaluation Criteria in Solid Tumors (RECIST). Radiologic assessments were performed every 8 weeks for 6 months and then every 12 weeks thereafter. Eligible patients were treated with Treprilimab at a dosage of 240mg intravenously every 3 weeks until they experienced disease progression or unacceptable toxicity. The primary end point of this study was objective response by the RECIST criteria , and the secondary end points were overall survival (OS), progression-free survival (PFS), duration of response and toxicity.

Eligibility criteria: Inclusion Criteria:

* ages from 18 years to 65 years.
* Histologically confirmed local recurrent/residual Nasopharyngeal carcinoma with previous re-irradiation.
* measurable disease at baseline on the basis of RECIST v1.1.
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* adequate organ function.
* anticipate survival≥3 months.

Exclusion Criteria:

* a diagnosis of immuno deﬁciency or systemic corticosteroid therapy within 14 days of study start.
* prior anticancer monoclonal antibody therapy within 4 weeks of study start.
* any anticancer therapy within 4 weeks preceding the study start.
* therapy with any other immune checkpoint inhibitor.
* active autoimmune disease, interstitial lung disease, known additional malignancy that was progressing or that required active treatment.
* not received platinum based chemotherapy previously.
* confirmed systemic metastasis
* HBV positive and Child-Pugh B or C cirrhosis
* HCV positive and Child-Pugh B or C cirrhosis

Primary outcomes:
measure: objective response rate
timeFrame: Response was assessed by magnetic resonance imaging every 8 weeks for the ﬁrst 6 months and every 12 weeks thereafter.
Secondary outcomes:
measure: PFS
timeFrame: time from enrollment to the ﬁrst documented progression of disease or death from any cause)
measure: OS
timeFrame: time from enrollment to death from any cause
measure: Number of participants with treatment-related adverse events
timeFrame: through the study and for 30 days after treatment discontinuation (90 days for serious AEs).
Other outcomes:
Locations:
Study officials:
References:
citation: Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018 May 10;36(14):1412-1418. doi: 10.1200/JCO.2017.77.0388. Epub 2018 Mar 27.
citation: Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24.
citation: Chan AT, Hsu MM, Goh BC, Hui EP, Liu TW, Millward MJ, Hong RL, Whang-Peng J, Ma BB, To KF, Mueser M, Amellal N, Lin X, Chang AY. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol. 2005 May 20;23(15):3568-76. doi: 10.1200/JCO.2005.02.147. Epub 2005 Apr 4.
citation: Zhou Y, Miao J, Wu H, Tang H, Kuang J, Zhou X, Peng Y, Hu D, Shi D, Deng W, Cao X, Zhao C, Xie C. PD-1 and PD-L1 expression in 132 recurrent nasopharyngeal carcinoma: the correlation with anemia and outcomes. Oncotarget. 2017 Apr 19;8(31):51210-51223. doi: 10.18632/oncotarget.17214. eCollection 2017 Aug 1.