Ignite Creation Date:
2024-05-06 @ 7:20 PM
Last Modification Date:
2024-10-26 @ 3:05 PM
Study NCT ID:
NCT05978050
Status:
RECRUITING
Last Update Posted:
2023-08-07
First Post:
2023-07-20
Brief Title:
Nimotuzumab Combined With Paclitaxel for Recurrent Metastatic Gastric or Esophagogastric Junction Adenocarcinoma
Sponsor:
Biotech Pharmaceutical Co Ltd
Organization:
Biotech Pharmaceutical Co Ltd
Study Overview
Official Title:
Nimotuzumab Combined With Paclitaxel as Second-line Treatment for Recurrent Metastatic Gastric or Esophagogastric Junction Adenocarcinoma With EGFR Over-expression A Randomized Double-blind Placebo-controlled Phase III Clinical Trial
Status:
RECRUITING
Status Verified Date:
2024-08
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:
NOTABLE-307
Brief Summary:
In order to evaluate the efficacy and safety of nimotuzumab combined with paclitaxel as second-line treatment for recurrent metastatic gastric or esophagogastric junction adenocarcinoma with EGFR over-expression investigators performed a randomized double-blind placebo-controlled phase III clinical trial Patients will be randomized 11 to receive nimotuzumab plus paclitaxel in the experimental group and placebo plus paclitaxel in the control group The primary endpoint of this study was OS and according to the results of the RAINBOW-Asia gastric cancer phase III clinical study the mOS of paclitaxel single-agent second-line treatment for gastric cancer was 792 months assuming that the mOS increased to 1092 months after the addition of nimotuzumab Using the survival module in the PASS15 software the two-sided test level was set α005 β020 enrolled for 2 years followed up for 15 years the dropout rate was 5 the sample size including interim analysis was 354 cases The secondary endpoints are progression-free survival PFS objective response rate ORR duration of response DOR disease control rate DCR patient reported outcome PRO and safety
Detailed Description:
Study design
This study is a prospective randomized double-blind placebo-controlled trial designed to evaluate the efficacy and safety of nimotuzumab combined with paclitaxel as second-line treatment for recurrent metastatic gastric or esophagogastric junction adenocarcinoma with EGFR over-expressionA total of 354 patients with recurrent metastatic gastric or esophagogastric junction adenocarcinoma with EGFR over-expression are expected to be enrolled Patients will be randomized 11 to receive nimotuzumab 600 mg for the first dose then 400 mg weekly plus paclitaxel 80 mgm2 on day 1 8 and 15 every 4 weeks as a cycle in the experimental group and placebo plus paclitaxel same as experimental group in the control group The study will be randomized by stratified block randomization stratification factors included ECOG PS 0 vs 1 first-line immunotherapy yes vs no and EGFR expression status IHC 2 vs 3 Treatment will continue until disease progression intolerance or patient withdrawal from the trial and each patient will be followed up until death loss to follow-up or the end of study
Quality Assurance plan According to the GCPs guidelines sponsors are responsible for using and maintaining quality assurance and quality control systems in accordance with the corresponding standard operating procedures SOPs The sponsor or sponsors representative shall conduct quality control at every stage of data processing to ensure the accuracy consistency completeness and reliability of the data In addition the sponsor or its representative the appropriate regulatory body may conduct audits andor inspections of the research process During audits andor regulatory inspections authorized sponsor representatives and relevant regulatory authorities have access to all research-related documents
Data checks
Investigators should collect complete participant data as required by the protocol recorded in the original record This study will use an electronic data acquisition EDC system and the library builder will build an electronic database according to the plan set up the corresponding logic verification and data management personnel will conduct data verification according to the corresponding verification plan
Source data verification
The research data will be entered into the eCRF by the researcher or authorized research center staff Investigators review the data to ensure the accuracy of all data entered into the eCRF The eCRF will be reviewed by the Inspector and assessed for completeness and consistency and the Auditor will compare the eCRF with the original documentation to ensure consistency of critical data All data entry correction and modification will be the responsibility of the researcher or its designee and the supervisor will not have this authority The data in the eCRF is submitted to the data server and any changes to the data will be recorded in the audit track that is the reason for the change the operator account number the modification time and date will be recorded If there is a data challenge the monitor medical or data management personnel will issue the challenge in the EDC according to the corresponding verification plan and the research center staff will be responsible for answering the question and conduct data verification from multiple parties and angles to ensure data quality After all data has been entered into the EDC in its entirety the monitor has completed the SDV on all data in the EDC the medical and data administrator has completed the review of all data in the EDC and all challenges have been closed the data administrator freezes the data
Data dictionary
The combined medication and medical history will be encoded using the Anatomical Therapeutic and Chemical Taxonomy of Drugs ATC 2021 and above and the Regulatory Activities Medical Dictionary MedDRA V240 and above respectively
Standard Operating Procedures
Informed consent approved by the Independent Ethics Committee IECInstitutional Review Board IRB must be obtained prior to carrying out any research-specific procedures Potentially eligible subjects will be screened within 4 weeks prior to the first dose and after qualified subject screening they will be enrolled through an interactive web response system IWRS Investigators should collect complete participant data eg laboratory tests vital signs physical examination electrocardiogram imaging tests adverse effects quality of life assessment scale evaluation etc as required by the protocol and record them in the original record
Investigators are required to submit a completed eCRF for each participant enrolled in the study Study numbers and subject numbers submitted with the eCRF should be carefully verified and all private information including subject names removed or rendered illegible to protect subject privacy When researching data entry into eCRF the system will automatically add the identity of the data entry user by the ID of the login user The investigator proves that it has reviewed the record through an electronic signature record and guarantees the accuracy of the data in the record After all data in the EDC is reviewed and all doubts have been closed the data is locked and analyzed
Adverse events were monitored throughout the study and it was the responsibility of the investigator to document all AEs observed during the study From the beginning of the subjects signing of informed consent to 30 days after the last dose of the investigational drug all AEs regardless of severity and causal relationship with the investigational drug need to be recorded in the original data and the corresponding AE page in the eCRF According to the relevant regulations of ICH and China GCP 2020 edition during this study investigators should complete the SAE report form provided by the sponsor and report to the sponsor in writing within 24 hours after learning of SAE or relevant new follow-up information
Sample size
The primary endpoint of this study was OS and according to the results of the RAINBOW-Asia gastric cancer phase III clinical study the mOS of paclitaxel single-agent second-line treatment for gastric cancer was 792 months assuming that the mOS increased to 1092 months after the addition of nimotuzumab and an interim analysis was set up during the trial Using the survival module in the PASS15 software the two-sided test level was set α005 β020 enrolled for 2 years followed up for 15 years the dropout rate was 5 the single-stage sample size was 354 cases and the required sample size for each group was 177
Plan for missing data
For participants who had not reported death at the time of analysis the last known surviving follow-up date was used as the censoring date For subjects who have not yet progressed the date of the last radiographic evaluation is used as the date of censoring For participants who had not undergone tumour assessment after baseline the date of randomisation was used as the date of censoring
Statistical analysis plan
The main overall survival OS analysis will be performed when 306 death events occur optimality test and blind sample size adjustment will be performed when 50 of death events occur
The primary endpoint of this study was mOS OS is the time between the date of randomization and death from any cause A stratified log-rank test was used to compare OS in the nilotuzumab plus paclitaxel and placebo plus paclitaxel group at a bilateral significance level of 005 The Kaplan-Meier KM method was used to estimate the OS of each treatment group and the Kaplan-Meier curve was plotted to show the survival difference description Efficacy estimates of OS will be expressed by risk ratios HR estimated by the hierarchical Cox proportional hazards model and their 95 confidence intervals
Secondary endpoints PFS ORR DOR DCRPRO and safety The Kaplan-Meier KM method was used to estimate the PFS of each treatment group and the Kaplan-Meier curve was plotted to show the difference description The stratification factors are the same as for OS analysis Efficacy estimates of PFS will be expressed by risk ratios HR estimated by the hierarchical Cox proportional hazards model and their 95 confidence intervals The Clopper-Pearson exact probability method was used to calculate the ORR and DCR estimates and their 95 confidence intervals for each treatment group respectively The Cochran-Mantel-Haenszel CMH method was used to calculate the odds ratio and its 95 confidence interval and p The stratification factors used in the CMH test are the same as in the OS analysis If the number of objective remission or disease control cases is insufficient to support the CMH test stratified precision testing is considered and precise confidence intervals for odds ratios are calculated DOR is only available for participants with objective response CRPR for descriptive analysis of TOR Results will be shown using the Kaplan-Meier method for each treatment group to estimate the median DOR and the distribution curve
This study is a prospective randomized double-blind placebo-controlled trial designed to evaluate the efficacy and safety of nimotuzumab combined with paclitaxel as second-line treatment for recurrent metastatic gastric or esophagogastric junction adenocarcinoma with EGFR over-expressionA total of 354 patients with recurrent metastatic gastric or esophagogastric junction adenocarcinoma with EGFR over-expression are expected to be enrolled Patients will be randomized 11 to receive nimotuzumab 600 mg for the first dose then 400 mg weekly plus paclitaxel 80 mgm2 on day 1 8 and 15 every 4 weeks as a cycle in the experimental group and placebo plus paclitaxel same as experimental group in the control group The study will be randomized by stratified block randomization stratification factors included ECOG PS 0 vs 1 first-line immunotherapy yes vs no and EGFR expression status IHC 2 vs 3 Treatment will continue until disease progression intolerance or patient withdrawal from the trial and each patient will be followed up until death loss to follow-up or the end of study
Quality Assurance plan According to the GCPs guidelines sponsors are responsible for using and maintaining quality assurance and quality control systems in accordance with the corresponding standard operating procedures SOPs The sponsor or sponsors representative shall conduct quality control at every stage of data processing to ensure the accuracy consistency completeness and reliability of the data In addition the sponsor or its representative the appropriate regulatory body may conduct audits andor inspections of the research process During audits andor regulatory inspections authorized sponsor representatives and relevant regulatory authorities have access to all research-related documents
Data checks
Investigators should collect complete participant data as required by the protocol recorded in the original record This study will use an electronic data acquisition EDC system and the library builder will build an electronic database according to the plan set up the corresponding logic verification and data management personnel will conduct data verification according to the corresponding verification plan
Source data verification
The research data will be entered into the eCRF by the researcher or authorized research center staff Investigators review the data to ensure the accuracy of all data entered into the eCRF The eCRF will be reviewed by the Inspector and assessed for completeness and consistency and the Auditor will compare the eCRF with the original documentation to ensure consistency of critical data All data entry correction and modification will be the responsibility of the researcher or its designee and the supervisor will not have this authority The data in the eCRF is submitted to the data server and any changes to the data will be recorded in the audit track that is the reason for the change the operator account number the modification time and date will be recorded If there is a data challenge the monitor medical or data management personnel will issue the challenge in the EDC according to the corresponding verification plan and the research center staff will be responsible for answering the question and conduct data verification from multiple parties and angles to ensure data quality After all data has been entered into the EDC in its entirety the monitor has completed the SDV on all data in the EDC the medical and data administrator has completed the review of all data in the EDC and all challenges have been closed the data administrator freezes the data
Data dictionary
The combined medication and medical history will be encoded using the Anatomical Therapeutic and Chemical Taxonomy of Drugs ATC 2021 and above and the Regulatory Activities Medical Dictionary MedDRA V240 and above respectively
Standard Operating Procedures
Informed consent approved by the Independent Ethics Committee IECInstitutional Review Board IRB must be obtained prior to carrying out any research-specific procedures Potentially eligible subjects will be screened within 4 weeks prior to the first dose and after qualified subject screening they will be enrolled through an interactive web response system IWRS Investigators should collect complete participant data eg laboratory tests vital signs physical examination electrocardiogram imaging tests adverse effects quality of life assessment scale evaluation etc as required by the protocol and record them in the original record
Investigators are required to submit a completed eCRF for each participant enrolled in the study Study numbers and subject numbers submitted with the eCRF should be carefully verified and all private information including subject names removed or rendered illegible to protect subject privacy When researching data entry into eCRF the system will automatically add the identity of the data entry user by the ID of the login user The investigator proves that it has reviewed the record through an electronic signature record and guarantees the accuracy of the data in the record After all data in the EDC is reviewed and all doubts have been closed the data is locked and analyzed
Adverse events were monitored throughout the study and it was the responsibility of the investigator to document all AEs observed during the study From the beginning of the subjects signing of informed consent to 30 days after the last dose of the investigational drug all AEs regardless of severity and causal relationship with the investigational drug need to be recorded in the original data and the corresponding AE page in the eCRF According to the relevant regulations of ICH and China GCP 2020 edition during this study investigators should complete the SAE report form provided by the sponsor and report to the sponsor in writing within 24 hours after learning of SAE or relevant new follow-up information
Sample size
The primary endpoint of this study was OS and according to the results of the RAINBOW-Asia gastric cancer phase III clinical study the mOS of paclitaxel single-agent second-line treatment for gastric cancer was 792 months assuming that the mOS increased to 1092 months after the addition of nimotuzumab and an interim analysis was set up during the trial Using the survival module in the PASS15 software the two-sided test level was set α005 β020 enrolled for 2 years followed up for 15 years the dropout rate was 5 the single-stage sample size was 354 cases and the required sample size for each group was 177
Plan for missing data
For participants who had not reported death at the time of analysis the last known surviving follow-up date was used as the censoring date For subjects who have not yet progressed the date of the last radiographic evaluation is used as the date of censoring For participants who had not undergone tumour assessment after baseline the date of randomisation was used as the date of censoring
Statistical analysis plan
The main overall survival OS analysis will be performed when 306 death events occur optimality test and blind sample size adjustment will be performed when 50 of death events occur
The primary endpoint of this study was mOS OS is the time between the date of randomization and death from any cause A stratified log-rank test was used to compare OS in the nilotuzumab plus paclitaxel and placebo plus paclitaxel group at a bilateral significance level of 005 The Kaplan-Meier KM method was used to estimate the OS of each treatment group and the Kaplan-Meier curve was plotted to show the survival difference description Efficacy estimates of OS will be expressed by risk ratios HR estimated by the hierarchical Cox proportional hazards model and their 95 confidence intervals
Secondary endpoints PFS ORR DOR DCRPRO and safety The Kaplan-Meier KM method was used to estimate the PFS of each treatment group and the Kaplan-Meier curve was plotted to show the difference description The stratification factors are the same as for OS analysis Efficacy estimates of PFS will be expressed by risk ratios HR estimated by the hierarchical Cox proportional hazards model and their 95 confidence intervals The Clopper-Pearson exact probability method was used to calculate the ORR and DCR estimates and their 95 confidence intervals for each treatment group respectively The Cochran-Mantel-Haenszel CMH method was used to calculate the odds ratio and its 95 confidence interval and p The stratification factors used in the CMH test are the same as in the OS analysis If the number of objective remission or disease control cases is insufficient to support the CMH test stratified precision testing is considered and precise confidence intervals for odds ratios are calculated DOR is only available for participants with objective response CRPR for descriptive analysis of TOR Results will be shown using the Kaplan-Meier method for each treatment group to estimate the median DOR and the distribution curve
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None