Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate the Safety and Efficacy of SH-1028 in Locally Advanced or Metastatic NSCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03823807
Recruitment Status : Not yet recruiting
First Posted : January 30, 2019
Last Update Posted : February 1, 2019
Sponsor:
Information provided by (Responsible Party):
Nanjing Sanhome Pharmaceutical, Co., Ltd.

Tracking Information
First Submitted Date  ICMJE January 22, 2019
First Posted Date  ICMJE January 30, 2019
Last Update Posted Date February 1, 2019
Estimated Study Start Date  ICMJE March 2019
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 28, 2019)
Objective Response Rate (ORR) [ Time Frame: Every 2 cycles (21 days for 1 cycle) until end of treatment, an average of 1 year. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2019)
  • Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: From Baseline up to 30 days after the last dose, an average of 1 year. ]
  • Maximum Plasma Concentration (Cmax) [ Time Frame: Part A: Day 1 of Cycle 1 and 2 (21 days for 1 cycle). ]
  • Area Under the Curve [AUC] [ Time Frame: Part A: Day 1 of Cycle 1 and 2 (21 days for 1 cycle). ]
  • Progression-free survival (PFS) [ Time Frame: Every 2 cycles (21 days for 1 cycle) until end of follow-up, an average of 1 year. ]
  • Duration of Response(DOR) [ Time Frame: Every 2 cycles (21 days for 1 cycle) until end of treatment, an average of 1 year. ]
  • Disease Control Rates(DCR) [ Time Frame: Every 2 cycles (21 days for 1 cycle) until end of treatment, an average of 1 year. ]
  • Overall survival(OS) [ Time Frame: Every 2 cycles (21 days for 1 cycle) until end of treatment; Every 12 weeks until end of follow-up, an average of 2 years. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 30, 2019)
  • Biomakers (eg. AF value of KRAS,MET mutation or other gene mutations ) of drug-resistance measured by next-generation sequencing (NGS). [ Time Frame: at end of treatment,an average of 1 years. ]
    optional,use NGS to analyse the gene associated with NSCLC and to determine the reason of SH-1028-resistance.
  • Minimum Plasma Concentration (Cmin) [ Time Frame: Before administration in Day 1 of cycle 2, 3 and 5 (21 days for 1 cycle). ]
Original Other Pre-specified Outcome Measures
 (submitted: January 28, 2019)
  • Biomakers (eg. KRAS and MET mutation) of efficacy/resistance measured by next-generation sequencing (NGS). [ Time Frame: From baseline up to end of treatment,an average of 2 years. ]
  • Minimum Plasma Concentration (Cmin) [ Time Frame: Before administration in Day 1 of cycle 2, 3 and 5 (21 days for 1 cycle). ]
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety and Efficacy of SH-1028 in Locally Advanced or Metastatic NSCLC
Official Title  ICMJE A Multicenter, Open-label, Phase II Study to Evaluate the Safety and Efficacy of SH-1028 in Locally Advanced or Metastatic NSCLC
Brief Summary A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of SH-1028 with Locally Advanced/Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene.
Detailed Description This is a multicenter, open-label, phase II study to evaluate the safety and efficacy of SH-1028 in locally advanced or metastatic NSCLC.The trail is divided into two parts:part A is dose extension phase,and Part B is expand sample size phase to confirm the efficacy of SH-1028.Patients must agree to provide a biopsy for central confirmation of T790M mutation status following confirmed disease progression on the most recent treatment regimen. The primary objective of the study is to assess the efficacy of SH-1028 by assessment of Objective Response Rate according to RECIST 1.1 by an Independent Central Review.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE Drug: SH-1028
Oral,100mg or 200mg ,QD, fasted
Study Arms  ICMJE Experimental: SH-1028
QD,Oral
Intervention: Drug: SH-1028
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: January 28, 2019)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18 years, both sexes.
  • Histological or cytological confirmation of metastatic or locally advanced, relapsed NSCLC that are not candidates for curative treatment.
  • Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR-TKI sensitivity (including exon 19 deletion, L858R, L861Q, G719X or dual mutation) for treatment-naive NSCLC patients (without systemic therapy or with relapse after previous surgery; patients with locally treatment for non-target lesions are accepted ).(This criteria applies to treatment-naïve NSCLC patients in Part B).
  • Patients must have confirmation of T790M+ mutation status, which have experienced disease progression while on a previous continuous treatment with an EGFR-TKI or clinical benefit from EGFR-TKI according to the Jackman criteria while on continuous treatment with an EGFR-TKI (PR/CR, or SD continued ≥6 months); Patients can receive more than one line of systemic therapy. (This criteria applies to EGFR-T790M+ patients in Part A and Part B).
  • ECOG score of 0-2 with a minimum life expectancy of 3 months.
  • At least 1 lesion that has not previously been irradiated, that can be accurately measured at Baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have short axis ≥ 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), which is suitable for accurately repeated measurements.
  • Adequate bone marrow reserve or organ function as demonstrated by the following laboratory values: a) absolute neutrophil count ≥ 1.5×109/L; b) platelet count ≥ 100×109/L; c) hemoglobin ≥ 90 g/L; d) ALT ≤ 2.5×ULN if no demonstrable liver metastases, or ALT ≤ 5×ULN in the presence of liver metastases; e) AST ≤ 2.5×ULN if no demonstrable liver metastases, or AST ≤ 5×ULN in the presence of liver metastases; f) Total bilirubin ≤ 1.5×ULN if no liver metastases or ≤ 3×ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases; g) Creatinine ≤ 1.5×ULN, or Creatinine > 1.5×ULN concurrent with creatinine clearance ≥ 50 ml/min (measured or calculated by the Cockcroft- Gault equation).
  • 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).
  • Do not anticipate other clinical trial in 1 month.
  • Patients must sign and date written informed consent prior to admission to the study.

Exclusion Criteria:

  • EGFR-TKI treatment within 8 days or approximately 5 times the half-life of the specific drug, whichever is longer, of the first dose study.
  • Any cytotoxic chemotherapy or immunological therapy used for a previous treatment regimen or clinical study within 21 days of the first dose of study treatment; Any target therapy(except EGFR-TKIs)and endocrine therapy used for a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
  • Ever used the third generation EGFR-TKI, such as Osimertinib, CO-1686, Avitinib, AST2818, HS-10296.
  • Major surgery within 4 weeks of the first dose of study treatment.
  • Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed within 4 weeks of the first dose of study treatment.
  • The patient is currently using (or cannot discontinue at least 1 week before the first dose of study treatment) a drug or herbal supplement known as a potent inhibitor or inducer of CYP3A4.
  • Use large doses of glucocorticoids (eg, >10 mg/day prednisone ) or other immunosuppressive agents within 4 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 or brain metastases unless asymptomatic, stable, and not requiring steroids , anticonvulsants and mannitol 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, 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:

    1. Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs), using the Screening clinic ECG machine and Fridericia's formula for QT interval correction.
    2. 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).
  • 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.
  • Have 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 to a drug with a similar chemical structure or class to SH-1028.
  • Women who are breast feeding.
  • Any disease or condition that, in the opinion of the Investigator, would compromise the safety of the patient or interfere with study assessments.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Caicun Zhou, MD +86-13301825532 caicunzhoudr@163.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03823807
Other Study ID Numbers  ICMJE SHC013-II-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Nanjing Sanhome Pharmaceutical, Co., Ltd.
Study Sponsor  ICMJE Nanjing Sanhome Pharmaceutical, Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Nanjing Sanhome Pharmaceutical, Co., Ltd.
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP