Safety and Tolerability of SH-1028 in Patients With Advanced Solid Cancer

NCT03618043 | Unknown Phase 1

• 1 other identifier: SHC013-I-02
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label study of SH-1028 with dose escalation cohorts in locally advanced solid cancer patients who have progressed following prior therapy with an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor (TKI) agent or standard treatment.

Conditions

Advanced Solid Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD)

  Within the first 28 days of treatment

• Incidence of Dose Limiting Toxicity (DLT)

  Within the first 28 days of treatment

Secondary Outcomes (5)

• 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

• Overall Response Rate

  12 months

• Disease control rates（DCR）

  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 (120mg,180mg,240mg,320mg) 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 and Patients with advanced malignant solid tumors who have failed standard treatment, or have no standard treatment regimen, or are not eligible for standard treatment at this stage.
• Confirmation that the tumor harbors an EGFR mutation known to be associated with EGFR TKI sensitivity :
• For NSCLC patients, 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; patients must have confirmation of T790M+ mutation status.
• For other solid cancer patients, they have failed standard treatment, or have no standard treatment regimen and have confirmation that mutation of EGFR pathway is negative.
• World Health Organization (WHO) performance status equal to 0-1.
• A minimum life expectancy of 12 weeks.
• At least 1 lesion that has not previously been irradiated.
• Adequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• Absolute neutrophil count \> 1.5 x 109/L.
• Platelet count \> 100 x 109/L.
• Hemoglobin \> 90 g/L (\< 9 g/dL).
• Alanine aminotransferase \< 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or \< 5 times the ULN in the presence of liver metastases.
• Aspartate aminotransferase \< 2.5 times the ULN if no demonstrable liver metastases or \< 5 times the ULN in the presence of liver metastases.
• Total bilirubin \< 1.5 times the ULN if no liver metastases or \< 3 times the ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases.

You may not qualify if:

• 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 radiation, cytotoxic chemotherapy, target medicines (except EGFR-TKI), endocrine therapy or immunotherapy used for a previous treatment regimen or clinical study within 28 days of the first dose of study treatment.
• 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 bp / mL ）.
• 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).
• 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.

Sponsors & Collaborators

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

Study Sites (1)

Shanghai east hospital

Shanghai, China

RECRUITING

MeSH Terms

Interventions

SH-1028

Study Officials

• JIN LI, MD

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

JIN LI, MD

CONTACT

021-38804518; lijin@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: August 1, 2018
• First Posted: August 7, 2018
• Study Start: September 13, 2018
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: January 29, 2019

Record last verified: 2018-08

Locations

CN (1)