Safety, Tolerability and Pharmacokinetics of SH-1028 in Patients With Advanced NSCLC

NCT03603262 | Unknown Phase 1 DMC

• 1 other identifier: SHC013-I-01
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label study of SH-1028 with dose escalation and dose expansion cohorts in locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients who have progressed following prior therapy with an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor (TKI) agent.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (5)

• Maximum tolerated dose (MTD)

  Within the first 28 days of treatment

• Incidence of Dose Limiting Toxicity (DLT)

  Within the first 28 days of treatment

• Area under the plasma concentration versus time curve (AUC) of SH-1028

  4 weeks

• Elimination half-life(T1/2) of SH-1028

  4 weeks

• Maximum (or peak) concentration of SH-1028

  4 weeks

Secondary Outcomes (4)

• Overall Response Rate (ORR)

  12 months

• Progression-free survival (PFS)

  12 months

• Disease control rates（DCR）

  12 months

• Overall survival（OS）

  12 months

Study Arms (1)

SH-1028

EXPERIMENTAL

Oral Once-Daily Administration of SH-1028

Drug: SH-1028

Interventions

SH-1028 DRUG

Starting dose 60mg,oral administered once daily.If tolerated subsequent cohorts will test increasing doses (100mg,200mg,300mg,400mg) of SH-1028.

SH-1028

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age from 18 to 75, both sexes.
• Histologically or cytologically documented NSCLC.
• Not amenable to radical therapy or stage IV.
• Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI, e.g., gefitinib or erlotinib. In addition, other lines of therapy may have been given(chemotherapy only accept first line).
• Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) or must have experienced 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 must have confirmation of tumor T790M+ mutation status.
• Patients also must have confirmation of tumor T790M+ mutation status.
• World Health Organization (WHO) performance status equal to 0-1 with no deterioration over the previous 2 weeks.
• A minimum life expectancy of 12 weeks.
• 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.
• 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 trail in 3 months.
• The patient must provide a written informed consent for genetic research.

You may not qualify if:

• Not Confirmed by pathology.
• An EGFR TKI within 8 days or approximately 5 times the half-life of the specific drug, whichever is longer, of the first dose of study treatment.
• Any cytotoxic chemotherapy used for a previous treatment regimen or clinical study within 21 days of the first dose of study treatment; Any target medicines used for a previous treatment regimen or clinical study within 14 days of the first dose of study treatment; withdrawal other clinical drugs or anti-cancer drugs less than 5 times the half-life.
• Ever used the third EGFR-TKI, such as AZD9291,CO-1686 or avitinib.
• 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 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 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 \<1×103 IU/ mL ,and HCVAb is positive but HCV-RNA\<103 IU/mL can be accepted.）.
• Any of the following cardiac criteria:
• 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.
• 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 \>250msec).

Sponsors & Collaborators

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

Study Sites (1)

Jiangsu Province Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Related Publications (1)

• He J, Ma P, Zhao D, Shi X, Guo R, Gao W, Shu Y. Safety, efficacy, and pharmacokinetics of SH-1028 in EGFR T790M-positive advanced non-small cell lung cancer patients: A dose-escalation phase 1 study. Cancer. 2023 May 15;129(10):1513-1522. doi: 10.1002/cncr.34697. Epub 2023 Feb 22.

  PMID: 36813747 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

SH-1028

Condition Hierarchy (Ancestors)

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

Study Officials

• SHU YONGQIAN, MD

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

SHU YONGQIAN, MD

CONTACT

+8613951017570; shuyongqian@csco.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2018
• First Posted: July 27, 2018
• Study Start: April 25, 2018
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: January 28, 2019

Record last verified: 2018-07

Locations

CN (1)