A Study of SH-1028 Tablets Versus Gefitinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer

NCT04239833 | Unknown Phase 3

• 1 other identifier: SHC013-III-01
• Study Type: interventional
• Target: 240
• Locations: 0 countries
• Sites: N/A

Brief Summary

To assess the efficacy and safety of SH-1028 tablets versus Gefitinib, a standard of care epidermal growth factor receptor tyrosine kinase inhibitor, in patients with locally advanced or Metastatic Non Small Cell Lung Cancer

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival (PFS)

  Progression-free survival was defined as the time from randomization until the date of objective disease progression regardless of whether the participant withdrew from randomized therapy and was used to assess the efficacy of SH-1028 tablets compared with Gefitinib (SoC EGFR-TKI therapy) as measured by PFS. The primary endpoint of PFS was based on Investigator assessment.

  At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.

Secondary Outcomes (9)

• Objective Response Rate (ORR)

  At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.

• Duration of Response (DoR)

  At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.

• Disease Control Rate (DCR)

  At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.

• Depth of Response（DepOR）

  At baseline and every 6 weeks relative to randomisation until progression，up to 24 months.

• Overall Survival (OS)

  From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 30 months)

Study Arms (2)

SH-1028 tablets+Placebo Gefitinib

EXPERIMENTAL

SH-1028 tablets (200 mg orally, once daily) plus placebo Gefitinib (250 mg orally, once daily), in accordance with the randomization schedule. Interventions: Drug: SH-1028 tablets 200 mg Drug: Placebo Gefitinib 250 mg

Drug: SH-1028 tablets; Drug: Placebo Gefitinib

Gefitinib+Placebo SH-1028 tablets

ACTIVE COMPARATOR

Gefitinib (250 mg orally, once daily) plus placebo SH-1028 tablets (200mg orally, once daily), in accordance with the randomisation schedule. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label SH-1028 tablets (crossover to active SH-1028 tablets). Interventions: Drug: Gefitinib 250 mg Drug: Placebo SH-1028 tablets 200mg

Drug: Placebo SH-1028 tablets; Drug: Gefitinib

Interventions

SH-1028 tablets DRUG

The initial dose of SH-1028 tablets is 200 mg once daily . A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

SH-1028 tablets+Placebo Gefitinib

Placebo SH-1028 tablets DRUG

The initial dose of Placebo SH-1028 tablets is 200 mg once daily . A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.

Gefitinib+Placebo SH-1028 tablets

Gefitinib DRUG

The initial dose of Gefitinib is 250 mg once daily . A cycle of treatment is defined as 21 days of once daily treatment. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label SH-1028 tablets (crossover to active SH-1028 tablets).

Gefitinib+Placebo SH-1028 tablets

Placebo Gefitinib DRUG

The initial dose of Gefitinib is 250 mg once daily . A cycle of treatment is defined as 21 days of once daily treatment.

SH-1028 tablets+Placebo Gefitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Male or female, aged at least 18 years.
• \. Pathologically or cytologically confirmed locally advanced or metastatic NSCLC (e.g. this may occur systemic recurrence after prior surgery for early stage disease or patients may be newly diagnosed with stage IIIB/IV disease). Patients must be treatment-naïve for locally advanced or metastatic NSCLC. Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy, investigational agents) provided all other entry criteria are satisfied.
• \. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either or in combination with other EGFR mutations assessed by central testing using tumour tissue sample or cytology sample.
• \. A ECOG performance status equal to 0-1 with a minimum life expectancy of 12 weeks.
• \. At least 1 lesion that has not previously been irradiated, that has not been chosen for biopsy during the study screening period, and that can be accurately measured at Baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), whichever is suitable for accurately repeated measurements.
• \. Adequate bone marrow reserve or organ function, as demonstrated by the following laboratory values:
• 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.
• \. 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 completion of study, 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 completion of study (i.e., condoms).

You may not qualify if:

• \. Treatment with any of the following, including any EGFR-TKI, systemic chemotherapy (except for relapsed patients at last 6 months after received post-surgery adjuvant 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.
• \. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study drug, with the exception of patients receiving radiation to \> 30% of the bone marrow or with a wide field of radiation 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.
• \. Treatment with large doses of glucocorticoids (eg, \>10 mg/day dexamethasone ) or other immunosuppressive agents within 2 weeks.
• \. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE), Grade 1, at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
• \. Spinal cord compression, meningeal metastases or brain metastases unless asymptomatic, s table, and not requiring steroids for at least 4 weeks prior to start of study treatment.
• \. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension or active bleeding diatheses, or which in the Investigator's opinion makes it undesirable for the patient to participate in the trial.
• \. Active infection (e.g., hepatitis B, hepatitis C or human immunodeficiency virus \[HIV\]). (HBsAg is positive but HBV-DNA \< ULN, and HCVAb is positive but HCV-RNA\<ULN can be accepted.）
• \. Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTcF) \> 470 msec obtained from 3 electrocardiograms (ECGs), using the Screening clinic 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) ≤ 40%.
• \. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.

Sponsors & Collaborators

• Nanjing Sanhome Pharmaceutical, Co., Ltd.: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

SH-1028; Gefitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Zhou Caicun, Professor

  Shanghai Pulmonary Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Han Luwei

CONTACT

86-15195873396; hanlw@sanhome.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: All trial personnel and participants were masked to treatment allocation, until unblinding due to progression disease or other Criteria of termination.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned to SH-1028 tablets arm or Gefitinib arm based on the mutation condition of EGFR (L858R or 19Del) and brain metastases (yes or no). The rate of SH-1028 tablets arm to Gefitinib arm is 2:1.

Study Record Dates

• First Submitted: January 2, 2020
• First Posted: January 27, 2020
• Study Start: January 31, 2020
• Primary Completion: January 31, 2022
• Study Completion: January 31, 2024
• Last Updated: January 27, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share