Ignite Creation Date:
2024-05-06 @ 4:10 PM
Last Modification Date:
2024-10-26 @ 2:05 PM
Study NCT ID:
NCT04898374
Status:
RECRUITING
Last Update Posted:
2022-08-17
First Post:
2021-05-13
Brief Title:
Induction Versus Adjuvant GemcitabineCisplatin in Locally Advanced Non-metastatic Nasopharyngeal Carcinoma
Sponsor:
Kuwait Cancer Control Center
Organization:
Kuwait Cancer Control Center
Study Overview
Official Title:
Induction Versus Adjuvant GemcitabineCisplatin in Locally Advanced Non-metastatic Nasopharyngeal Carcinoma A Randomized Phase III Trial
Status:
RECRUITING
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The standard of care for locally advanced nasopharyngeal carcinoma is radical chemoradiationCRTRecent advances in radiation techniques and supportive measures resulted in improvemnent of locoregional control and quality of lifeHowever distant failure is still the main challenging reason of poor survival
Addition of systemic therapy to concurrent CRT is widely used and accepted as an option to reduce these failures however selection of chemotherapy regimen and timing in relation to CRT is controversial
Doublet and triplet chemotherapy regimens using cisplatin and 5FU are throughly investigated in this settingInspite of significant improvement in disease free survival and overall survival they were poorly toleratedHenceminority of patients in the daily practice could tolerate those studied regimens as propsed
Recently in multicenter randomized trial Zhang and his group investigated gemcitabine and cisplatin as induction chemotherapy ICT added to CRTIt showed improvement in recurrence free survival and overall survivalMore importantly 967 of the experimental arm completed the treatment protocol
This was further confirmed by an updated network of meta analysis by Bongiovanni et alAgain the question of when is still validOur proposal is to compare tolerable regimen in induction versus adjuvant settings
Addition of systemic therapy to concurrent CRT is widely used and accepted as an option to reduce these failures however selection of chemotherapy regimen and timing in relation to CRT is controversial
Doublet and triplet chemotherapy regimens using cisplatin and 5FU are throughly investigated in this settingInspite of significant improvement in disease free survival and overall survival they were poorly toleratedHenceminority of patients in the daily practice could tolerate those studied regimens as propsed
Recently in multicenter randomized trial Zhang and his group investigated gemcitabine and cisplatin as induction chemotherapy ICT added to CRTIt showed improvement in recurrence free survival and overall survivalMore importantly 967 of the experimental arm completed the treatment protocol
This was further confirmed by an updated network of meta analysis by Bongiovanni et alAgain the question of when is still validOur proposal is to compare tolerable regimen in induction versus adjuvant settings
Detailed Description:
Background
Nasopharyngeal carcinoma NPC is one of the cancers which shows significant geographic prevalence variation Worldwide there were 130000 new cases in 2018As a non-endemic region only 35 new cases were diagnosed in Kuwait in the same year Nevertheless it accounts for 13 of cancer related mortality in Kuwait
Radical radiotherapy RT is the mainstay treatment of NPC for decades A high cure rate can be achieved for patients with early-stage The breakthrough in the management of NPC came with the intergroup study 009 which showed significant improved progression free survival with adding chemotherapy CTH to the radiation
As compared to RT alone concurrent chemoradiation CRT showed significant improvement in 10-year overall survival and progression free survival in meta-analysis of nasopharyngeal carcinoma MAC-NPC collaborative group Addition of systemic therapy to concurrent CRT was the proposed solution to treatment failures whether in the induction ICT or adjuvant ACT settings However ICT or ACT in NPC remains controversial largely due to inconsistent results of several prospective randomized trials
The above-mentioned MAC-NPC group reviewed six clinical trials in which CRT followed by ACT was compared with RT alone administrated without concurrent or adjuvant chemotherapy Overall survival OS was significantly improved compared with RT alone 10-year overall survival 57 versus 431 HR 065 95 CI 056-076 as well as 10-year progression-free survival PFS 532 versus 385
However this was not consistent in endemic areas with high prevalence of Epstein-Barr virus EBV which is known causative for NPC Chen et al reported in a Chinese phase III trial 508 patients with advanced NPC randomized to ACT cisplatin plus fluorouracil vs observation following CRT with weekly cisplatin There was no improvement in the five-year failure-free rate with ACT compared with CRT alone five-year rate 75 versus 71 HR 088 95 CI 064-122 Later from the same endemic region Sun Yat-sen university conducted a multi center phase III clinical trial in which 480 patients stage III to IVB node-positive NPC were randomly assigned to ICT followed by CRT versus CRT alone This study showed improvement of recurrence-free survival RFS and distant RFS
Another reason for reluctancy to adopt ICT or ACT in the management of advanced NPC is the morbidity of current chemotherapy regimens The high toxicity profile with some of these regimens was the real obstacle toward the use of them In previous studies the back bone for adjuvant or induction chemotherapy in NPC has been platinum and 5-fluoruracil with or without a taxane This regimen was poorly tolerated with only 40-60 of patients could complete their preplanned course of treatment in many trials
Recently in multicenter randomized trial Zhang and his group compared gemcitabine and cisplatin as ICT plus CRT with CRT alone The 3-year RFS was 853 in the induction group and 765 in the standard-therapy group HR 051 95 CI 034 to 077 P0001 Overall survival at 3 years was 946 and 903 respectively HR 043 95 CI 024 to 077 What is more important is that 967 of the experimental arm completed 3 cycles of ICT
On behalf of the Nasopharyngeal Cancer Portal Group of Investigators Bossi colleagues from Europe Kuwait Jordan Turkey and USA assessed the impact of treatment intensity within a large retrospective multicenter cohort nasopharyngeal cancer in non-endemic areas Our group shared in this pooled analysis and the data showed a higher rate of death and recurrence with non-intensive treatment defined as no added systemic treatment to CRT
Ongoing Phase 3 Trials exploring ICT or ACT in NPC
There are multiple phase 3 trials ongoing to refine the ICT or ACT approach Sun Yat-sen University is conducting a study comparing TPF with PF as ICT regimen in stage IVa-b NPC NCT02940925 They also explore the effect of triple combination of ICT CRT and ACT in high risk NPC NCT02621970 Another comparison between induction TPF vs adjuvant PF is recruiting NCT03306121 Fudan University also from China exploring maintenance gemcitabine after radical treatment in N3 disease NCT03403829 Jiangxi Provincial Cancer Hospital testing adding neoadjuvant and adjuvant PD-1 inhibitor to ICT-CRT NCT04557020 Another promising strategy to control the distant failures in locally advanced NPC is to employ immunotherapy in the primary treatment There are many ongoing trials exploring this strategy mainly in China However the validity in endemic vs non-endemic regions should be taken with caution
Aim of the study In our proposal we are trying to compare the efficacy and tolerability of ICT followed by CRT with CRT followed ACT in locally advanced NPC
Nasopharyngeal carcinoma NPC is one of the cancers which shows significant geographic prevalence variation Worldwide there were 130000 new cases in 2018As a non-endemic region only 35 new cases were diagnosed in Kuwait in the same year Nevertheless it accounts for 13 of cancer related mortality in Kuwait
Radical radiotherapy RT is the mainstay treatment of NPC for decades A high cure rate can be achieved for patients with early-stage The breakthrough in the management of NPC came with the intergroup study 009 which showed significant improved progression free survival with adding chemotherapy CTH to the radiation
As compared to RT alone concurrent chemoradiation CRT showed significant improvement in 10-year overall survival and progression free survival in meta-analysis of nasopharyngeal carcinoma MAC-NPC collaborative group Addition of systemic therapy to concurrent CRT was the proposed solution to treatment failures whether in the induction ICT or adjuvant ACT settings However ICT or ACT in NPC remains controversial largely due to inconsistent results of several prospective randomized trials
The above-mentioned MAC-NPC group reviewed six clinical trials in which CRT followed by ACT was compared with RT alone administrated without concurrent or adjuvant chemotherapy Overall survival OS was significantly improved compared with RT alone 10-year overall survival 57 versus 431 HR 065 95 CI 056-076 as well as 10-year progression-free survival PFS 532 versus 385
However this was not consistent in endemic areas with high prevalence of Epstein-Barr virus EBV which is known causative for NPC Chen et al reported in a Chinese phase III trial 508 patients with advanced NPC randomized to ACT cisplatin plus fluorouracil vs observation following CRT with weekly cisplatin There was no improvement in the five-year failure-free rate with ACT compared with CRT alone five-year rate 75 versus 71 HR 088 95 CI 064-122 Later from the same endemic region Sun Yat-sen university conducted a multi center phase III clinical trial in which 480 patients stage III to IVB node-positive NPC were randomly assigned to ICT followed by CRT versus CRT alone This study showed improvement of recurrence-free survival RFS and distant RFS
Another reason for reluctancy to adopt ICT or ACT in the management of advanced NPC is the morbidity of current chemotherapy regimens The high toxicity profile with some of these regimens was the real obstacle toward the use of them In previous studies the back bone for adjuvant or induction chemotherapy in NPC has been platinum and 5-fluoruracil with or without a taxane This regimen was poorly tolerated with only 40-60 of patients could complete their preplanned course of treatment in many trials
Recently in multicenter randomized trial Zhang and his group compared gemcitabine and cisplatin as ICT plus CRT with CRT alone The 3-year RFS was 853 in the induction group and 765 in the standard-therapy group HR 051 95 CI 034 to 077 P0001 Overall survival at 3 years was 946 and 903 respectively HR 043 95 CI 024 to 077 What is more important is that 967 of the experimental arm completed 3 cycles of ICT
On behalf of the Nasopharyngeal Cancer Portal Group of Investigators Bossi colleagues from Europe Kuwait Jordan Turkey and USA assessed the impact of treatment intensity within a large retrospective multicenter cohort nasopharyngeal cancer in non-endemic areas Our group shared in this pooled analysis and the data showed a higher rate of death and recurrence with non-intensive treatment defined as no added systemic treatment to CRT
Ongoing Phase 3 Trials exploring ICT or ACT in NPC
There are multiple phase 3 trials ongoing to refine the ICT or ACT approach Sun Yat-sen University is conducting a study comparing TPF with PF as ICT regimen in stage IVa-b NPC NCT02940925 They also explore the effect of triple combination of ICT CRT and ACT in high risk NPC NCT02621970 Another comparison between induction TPF vs adjuvant PF is recruiting NCT03306121 Fudan University also from China exploring maintenance gemcitabine after radical treatment in N3 disease NCT03403829 Jiangxi Provincial Cancer Hospital testing adding neoadjuvant and adjuvant PD-1 inhibitor to ICT-CRT NCT04557020 Another promising strategy to control the distant failures in locally advanced NPC is to employ immunotherapy in the primary treatment There are many ongoing trials exploring this strategy mainly in China However the validity in endemic vs non-endemic regions should be taken with caution
Aim of the study In our proposal we are trying to compare the efficacy and tolerability of ICT followed by CRT with CRT followed ACT in locally advanced NPC
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None