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SH-1028 Tablets Versus Placebo as Adjuvant Therapy in Resected Stage II-IIIB NSCLC With Sensitizing EGFR Mutations

Primary Purpose

Non-small Cell Lung Cancer

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
SH-1028 tablets
Placebo SH-1028 tablets
Sponsored by
Nanjing Sanhome Pharmaceutical, Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female, aged at least 18 years, younger than 75 years. Histologically confirmed diagnosis of primary non-small lung cancer (NSCLC) on predominantly non-squamous histology. Before surgery or randomization, MRI or CT scan of the brain and bone scan must be done to exclude metastases. Complete resection (R0) and systematic lymphadenectomy are mandatory: all surgical margins must be negative for tumor, and there should be no extranodal invasion of the mediastinal lymph nodes or marginal lymph nodes. Patients with postoperative pathological confirmation of stage II, IIIA and IIIB (only T3N2M0) are eligible. Patients must harbor one of the two common sensitizing EGFR mutations (Ex19del, L858R), either alone or in combination with other EGFR mutations including T790M, the mutations should be confirmed by the central laboratory. Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization. A ECOG performance status equal to 0-1 with a minimum life expectancy of 12 weeks and no deterioration over the past 2 weeks. Adequate bone marrow reserve or organ function, as demonstrated by the following laboratory values (no corrective treatment allowed within one week before blood sampling): Absolute neutrophil count (ANC)≥1.5×10^9 /L Platelet count ≥100×10^9 /L Hemoglobin ≥90 g/L Alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) if no demonstrable liver metastases or ≤ 5 × ULN in the presence of liver metastases Aspartate aminotransferase (AST) ≤ 2.5 × ULN if no demonstrable liver metastases or ≤ 5 × ULN in the presence of liver metastases Total bilirubin (TBL) ≤ 1.5 × ULN if no liver metastases or ≤ 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases Creatinine ≤ 1.5 × ULN concurrent with creatinine clearance ≥ 50 mL/min (measured or calculated by the Cockcroft-Gault equation); confirmation of creatinine clearance is only required when creatinine is ≤ 1.5×ULN Serum albumin (ALB) ≥28 g/L Coagulation function: International standardized ratio (INR) ≤1.5, activated partial thromboplastin time (APTT) ≤1.5×ULN Females of child-bearing potential should be using adequate contraceptive measures throughout the study, should not be breast feeding during the study and until 6 months after treatment, and must have a negative pregnancy test prior to start of dosing. Male patients should be willing to use barrier contraception during the study and until 6 months after treatment. Patients must sign and date written informed consent prior to admission to the study. Exclusion Criteria: Patients with unresectable or metastatic lesions, residual lesions after surgery, or those who have had only segmentectomies or wedge resection. Giant mediastinal lymph node metastasis at a single station or mediastinal lymph node fusion into a cluster at multiple stations; lesions invade the heart, aorta, esophagus, or pulmonary veins; Carcinoma of superior lung sulci. Treatment with any of the following (except for standard platinum -based adjuvant chemotherapy), including any EGFR-TKI, systemic chemotherapy,immunotherapy, targeted therapy and anti-tumor traditional Chinese medicine therapy. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug. The patient is currently using (or cannot discontinue at least 1 week before the first dose of study drug) a drug or herbal supplement known as a potent inhibitor or inducer of CYP3A4. Severe infections occurred within 4 weeks or active infections that received therapeutic intravenous or oral antibiotics within 2 weeks before the first dose. Any evidence of active infection (including hepatitis B, hepatitis C, and human immunodeficiency virus). Patients received continuous steroid therapy for more than 30 days within 30 days before the first dose; require long-term (≥30 days) steroid therapy; with acquired or congenital immunodeficiency diseases or have a history of organ transplantation. Severe or uncontrolled systemic diseases, including hypertension or diabetes. Any of the following cardiac criteria: Mean resting corrected QT interval (QTcF) > 470 msec obtained from 3 electrocardiograms (ECGs), using the Screening clinic's ECG machine and Fridericia's formula for QT interval correction. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250 msec). Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval. Left ventricular ejection fraction (LVEF) <50%. Receiving or requiring drugs known to prolong the QT interval or possibly cause tip torsion ventricular tachycardia during the study. History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. History of any other malignant tumor within five years (except clinically cured cervical carcinoma in situ, basal cells or squamous epithelial skin cancer). Any seriously abnormal gastrointestinal function would affect uptake, transport and absorption of the drug, such as inability to swallow the study medication, refractory nausea and vomiting, previous significant bowel resection, Recurrent diarrhea, atrophic gastritis (age < 60 years), unhealed serious gastric diseases, Crohn's disease or ulcerative colitis. History of hypersensitivity to any active or inactive ingredient of SH-1028 or drug with a similar chemical structure or class to SH-1028. Any severe and uncontrolled ocular disease that may, in the Investigator's opinion, present a specific risk to the patient's safety. Participating in another clinical trial within 4 weeks before the first dose (excluding retrospective observational studies without intervention); within 5 half-lives of other study drugs. Hepatic encephalopathy, hepatorenal syndrome, or ≥Child-Pugh grade B cirrhosis. Lactating Women. Any disease or condition that, in the opinion of the Investigator, would compromise the safety of the patient or interfere with study assessments.

Sites / Locations

  • Shanghai Pulmonary HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SH-1028 tablets

Placebo SH-1028 tablets

Arm Description

Outcomes

Primary Outcome Measures

Disease free survival (DFS) assessed by Independent Review Committee (IRC)
Disease-free survival is defined as the time from randomization until the date of the recurrence of tumor or death. The primary endpoint of DFS was based on the assessment of IRC.

Secondary Outcome Measures

Disease free survival (DFS) assessed by investigators
The secondary endpoint of DFS was based on the assessment of investigators.
DFS rate at 2, 3 and 5 years assessed by IRC
DFS rate at 2, 3 and 5 years is defined as the proportion of patients alive and disease free at 2, 3 and 5 years, respectively.
Overall survival (OS)
Overall survival is defined as the time from the date of randomization until death from any cause.
OS rate at 5 years
OS rate at 5 years is defined as the proportion of patients alive at 5 years.
Incidence rate of adverse events (AEs)
AEs are assessed according to CTCAE v5.0.
Plasma concentrations of SH-1028 and its major metabolites
This is defined as the pharmacokinetics parameters derived from plasma concentrations of SH-1028 and its metabolites, Imp2 and Imp3.

Full Information

First Posted
August 8, 2023
Last Updated
October 6, 2023
Sponsor
Nanjing Sanhome Pharmaceutical, Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT06080776
Brief Title
SH-1028 Tablets Versus Placebo as Adjuvant Therapy in Resected Stage II-IIIB NSCLC With Sensitizing EGFR Mutations
Official Title
A Phase III, Double-blind, Randomised Study of SH-1028 Tablets Versus Placebo as Adjuvant Therapy in Resected Stage II-IIIB Non-Small Cell Lung Cancer With Sensitizing EGFR Mutations
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 11, 2023 (Actual)
Primary Completion Date
February 1, 2028 (Anticipated)
Study Completion Date
February 1, 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanjing Sanhome Pharmaceutical, Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To assess the efficacy and safety of SH-1028 tablets versus placebo in stage II-IIIB non-small cell lung cancer (NSCLC) patients with sensitizing epidermal growth factor receptor (EGFR) mutations, following complete tumor resection, with or without adjuvant chemotherapy.
Detailed Description
This is a Phase III, multi-center, double-blind, randomized study assessing the efficacy and safety of SH-1028 tablets (200 mg orally, once daily) versus placebo in stage II-IIIB NSCLC with sensitizing EGFR mutations, following complete tumor resection, with or without adjuvant chemotherapy (2~4 cycles of platinum-based doublet).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
242 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SH-1028 tablets
Arm Type
Experimental
Arm Title
Placebo SH-1028 tablets
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
SH-1028 tablets
Intervention Description
The initial dose of SH-1028 tablets is 200 mg once daily.
Intervention Type
Drug
Intervention Name(s)
Placebo SH-1028 tablets
Intervention Description
Placebo SH-1028 tablets.
Primary Outcome Measure Information:
Title
Disease free survival (DFS) assessed by Independent Review Committee (IRC)
Description
Disease-free survival is defined as the time from randomization until the date of the recurrence of tumor or death. The primary endpoint of DFS was based on the assessment of IRC.
Time Frame
From the time of randomization to the recurrence of tumor or death, through study completion, an average of 5 years
Secondary Outcome Measure Information:
Title
Disease free survival (DFS) assessed by investigators
Description
The secondary endpoint of DFS was based on the assessment of investigators.
Time Frame
From the time of randomization to the recurrence of tumor or death, through study completion, an average of 5 years
Title
DFS rate at 2, 3 and 5 years assessed by IRC
Description
DFS rate at 2, 3 and 5 years is defined as the proportion of patients alive and disease free at 2, 3 and 5 years, respectively.
Time Frame
From the time of randomization to the recurrence of tumor or death, up to 5 years
Title
Overall survival (OS)
Description
Overall survival is defined as the time from the date of randomization until death from any cause.
Time Frame
From the time of randomization to death, through study completion, an average of 5 years
Title
OS rate at 5 years
Description
OS rate at 5 years is defined as the proportion of patients alive at 5 years.
Time Frame
From the time of randomization to death, up to 5 years
Title
Incidence rate of adverse events (AEs)
Description
AEs are assessed according to CTCAE v5.0.
Time Frame
From the screening period to 28 days after treatment discontinuation
Title
Plasma concentrations of SH-1028 and its major metabolites
Description
This is defined as the pharmacokinetics parameters derived from plasma concentrations of SH-1028 and its metabolites, Imp2 and Imp3.
Time Frame
The specified time points of blood sampling, up to 36 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, aged at least 18 years, younger than 75 years. Histologically confirmed diagnosis of primary non-small lung cancer (NSCLC) on predominantly non-squamous histology. Before surgery or randomization, MRI or CT scan of the brain and bone scan must be done to exclude metastases. Complete resection (R0) and systematic lymphadenectomy are mandatory: all surgical margins must be negative for tumor, and there should be no extranodal invasion of the mediastinal lymph nodes or marginal lymph nodes. Patients with postoperative pathological confirmation of stage II, IIIA and IIIB (only T3N2M0) are eligible. Patients must harbor one of the two common sensitizing EGFR mutations (Ex19del, L858R), either alone or in combination with other EGFR mutations including T790M, the mutations should be confirmed by the central laboratory. Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization. A ECOG performance status equal to 0-1 with a minimum life expectancy of 12 weeks and no deterioration over the past 2 weeks. Adequate bone marrow reserve or organ function, as demonstrated by the following laboratory values (no corrective treatment allowed within one week before blood sampling): Absolute neutrophil count (ANC)≥1.5×10^9 /L Platelet count ≥100×10^9 /L Hemoglobin ≥90 g/L Alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) if no demonstrable liver metastases or ≤ 5 × ULN in the presence of liver metastases Aspartate aminotransferase (AST) ≤ 2.5 × ULN if no demonstrable liver metastases or ≤ 5 × ULN in the presence of liver metastases Total bilirubin (TBL) ≤ 1.5 × ULN if no liver metastases or ≤ 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases Creatinine ≤ 1.5 × ULN concurrent with creatinine clearance ≥ 50 mL/min (measured or calculated by the Cockcroft-Gault equation); confirmation of creatinine clearance is only required when creatinine is ≤ 1.5×ULN Serum albumin (ALB) ≥28 g/L Coagulation function: International standardized ratio (INR) ≤1.5, activated partial thromboplastin time (APTT) ≤1.5×ULN Females of child-bearing potential should be using adequate contraceptive measures throughout the study, should not be breast feeding during the study and until 6 months after treatment, and must have a negative pregnancy test prior to start of dosing. Male patients should be willing to use barrier contraception during the study and until 6 months after treatment. Patients must sign and date written informed consent prior to admission to the study. Exclusion Criteria: Patients with unresectable or metastatic lesions, residual lesions after surgery, or those who have had only segmentectomies or wedge resection. Giant mediastinal lymph node metastasis at a single station or mediastinal lymph node fusion into a cluster at multiple stations; lesions invade the heart, aorta, esophagus, or pulmonary veins; Carcinoma of superior lung sulci. Treatment with any of the following (except for standard platinum -based adjuvant chemotherapy), including any EGFR-TKI, systemic chemotherapy,immunotherapy, targeted therapy and anti-tumor traditional Chinese medicine therapy. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study drug. The patient is currently using (or cannot discontinue at least 1 week before the first dose of study drug) a drug or herbal supplement known as a potent inhibitor or inducer of CYP3A4. Severe infections occurred within 4 weeks or active infections that received therapeutic intravenous or oral antibiotics within 2 weeks before the first dose. Any evidence of active infection (including hepatitis B, hepatitis C, and human immunodeficiency virus). Patients received continuous steroid therapy for more than 30 days within 30 days before the first dose; require long-term (≥30 days) steroid therapy; with acquired or congenital immunodeficiency diseases or have a history of organ transplantation. Severe or uncontrolled systemic diseases, including hypertension or diabetes. Any of the following cardiac criteria: Mean resting corrected QT interval (QTcF) > 470 msec obtained from 3 electrocardiograms (ECGs), using the Screening clinic's ECG machine and Fridericia's formula for QT interval correction. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250 msec). Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval. Left ventricular ejection fraction (LVEF) <50%. Receiving or requiring drugs known to prolong the QT interval or possibly cause tip torsion ventricular tachycardia during the study. History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. History of any other malignant tumor within five years (except clinically cured cervical carcinoma in situ, basal cells or squamous epithelial skin cancer). Any seriously abnormal gastrointestinal function would affect uptake, transport and absorption of the drug, such as inability to swallow the study medication, refractory nausea and vomiting, previous significant bowel resection, Recurrent diarrhea, atrophic gastritis (age < 60 years), unhealed serious gastric diseases, Crohn's disease or ulcerative colitis. History of hypersensitivity to any active or inactive ingredient of SH-1028 or drug with a similar chemical structure or class to SH-1028. Any severe and uncontrolled ocular disease that may, in the Investigator's opinion, present a specific risk to the patient's safety. Participating in another clinical trial within 4 weeks before the first dose (excluding retrospective observational studies without intervention); within 5 half-lives of other study drugs. Hepatic encephalopathy, hepatorenal syndrome, or ≥Child-Pugh grade B cirrhosis. Lactating Women. Any disease or condition that, in the opinion of the Investigator, would compromise the safety of the patient or interfere with study assessments.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kun Cao
Phone
86-15776680370
Email
caokun@sanhome.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Caicun Zhou, Professor
Organizational Affiliation
Shanghai Pulmonary Hospital, Shanghai, China
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Daqiang Sun, Professor
Organizational Affiliation
Tianjin Chest Hospital, Tianjin, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Pulmonary Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200433
Country
China
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

SH-1028 Tablets Versus Placebo as Adjuvant Therapy in Resected Stage II-IIIB NSCLC With Sensitizing EGFR Mutations

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