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Clinical Study of HEC68498 in Patients With Advanced Refractory Solid Tumors

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: NCT04324372
Recruitment Status : Recruiting
First Posted : March 27, 2020
Last Update Posted : March 27, 2020
Sponsor:
Information provided by (Responsible Party):
Sunshine Lake Pharma Co., Ltd.

Brief Summary:
Clinical study of HEC68498 in patients with advanced refractory solid tumors. The primary objective is to determine the maximum tolerated dose and dose limiting toxicity of HEC68498 in patients with advanced refractory solid tumors

Condition or disease Intervention/treatment Phase
Advanced Refractory Solid Tumors Drug: HEC68498 Phase 1

Detailed Description:
An open label multicentric Phase 1 study of HEC68498 in patients with advanced refractory solid tumors.The study will follow a 3+3 design until significant toxicity as described in the protocol and considering pharmacokinetics of the study drug determined from cohorts.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Multicentric Phase 1 Study of HEC68498 in Patients With Advanced Refractory Solid Tumors.
Actual Study Start Date : February 27, 2019
Estimated Primary Completion Date : February 27, 2021
Estimated Study Completion Date : October 17, 2021

Arm Intervention/treatment
Experimental: HEC68498
HEC68498 will be administered daily
Drug: HEC68498
HEC68498 is a potent,highly selective inhibitor of class 1 isozymes of phosphoinositide 3-kinase/mammalian(PI3K) and of the mammalian target of rapamycin (mTOR). It has shown good activity against fibrosis and inflammation in vitro and in vivo, with a lower effective dose and better efficacy than pirfenidone and nintedanib.




Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: 28 days ]
    Patients will receive study drug on a daily basis for 28 days according to the dose and schedule specified for a particular cohort of therapy. Toxicities observed in Cycle 0&1 will be considered for dose limiting toxicity (DLT) and Maximum tolerated dose (MTD)determination


Secondary Outcome Measures :
  1. Number of subject with adverse events [ Time Frame: up to 4 weeks after last dose ]
    The toxic effects of the drug would be assessed from adverse events, vital signs and by clinically significant changes in the laboratory evaluations.

  2. Objective response [ Time Frame: up to approximately 24 months ]
    Evaluation of Response: Clinical responses will be presented patient wise for different dose levels.

  3. AUC0-∞ [ Time Frame: up to approximately 4 weeks ]
    area under the concentration versus time curve (AUC) from time zero to infinity

  4. AUC0-t [ Time Frame: up to approximately 4 weeks ]
    AUC from time zero to the time of the last quantifiable concentration time zero to the time of the last quantifiable concentration

  5. Cmax [ Time Frame: up to approximately 4 weeks ]
    maximum observed plasma concentration

  6. tmax [ Time Frame: up to approximately 4 weeks ]
    time of the maximum observed plasma concentration

  7. t½ [ Time Frame: up to approximately 4 weeks ]
    apparent terminal elimination half-life

  8. Vz/F [ Time Frame: up to approximately 4 weeks ]
    apparent volume of distribution



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

(1)Target subjects

  1. 18 years of age ≤ age ≤ 70 years of age, regardless of gender;
  2. Patients with various types of advanced solid tumors confirmed by cytological or histological examination.

    Dose escalation test phase: including breast cancer, colorectal cancer, neuroendocrine tumors, etc .; Extended trial phase: limited to patients with HR + / HER2-, triple-negative, breast, colorectal, and neuroendocrine tumors, and patients with HR + / HER2- and colorectal cancer need genetic testing (blood and / or tumor tissue) PIK3CA mutations have been confirmed. Patients with triple negative breast cancer need genetic testing (blood and / or tumor tissue) to confirm PIK3CA / PTEN- mutations.

  3. Requires at least standard treatment failure or no standard treatment. Definition of treatment failure: a. Disease progression during or after treatment must have clear imaging or clinical evidence; b. Withdrawal from treatment due to intolerable response.
  4. According to the solid tumor evaluation criteria (RECIST 1.1), there is at least one measurable lesion.
  5. Relieve from previous chemotherapy, hormone therapy, targeted therapy, radiotherapy or surgical treatment of toxic reactions (according to CTCAE v5.0 grading ≤ 1 except hair loss)
  6. ECOG score is 0 or 1 (see Annex 2 for ECOG score criteria);
  7. Expected survival time ≥ 12 weeks;

(2) The subject must have proper organ function

  1. Blood routine: absolute neutrophil (ANC) ≥ 1.5 × 109 / L; platelet (PLT) ≥ 75 × 109 / L; hemoglobin (Hb) ≥ 90 g / L; Have received hematopoietic cell colony-stimulating growth factors (eg G-CSF, GM-CSF) or have not received blood transfusions. Erythropoietin or erythropoietin therapy can be maintained if it is used immediately before enrollment.
  2. Liver function: ALT and AST ≤ 2.5 × ULN (for patients with liver metastases, ALT and AST can be relaxed to ≤ 5.0 × ULN); serum bilirubin ≤ 1.5 × ULN;
  3. Renal function: serum creatinine ≤ 1.5 × ULN; or creatinine clearance (CrCl) ≥ 60 mL / min calculated according to the Cockcroft-Gault formula:

    Urine routine urinary protein ≤ 1+; if urinary routine urinary protein ≥ 2+, a 24-hour urine protein quantification is less than 1 g.

  4. Electrolyte: LLN ≤ blood potassium ≤ ULN;
  5. Coagulation function: international standardized ratio (INR) ≤ 1.5 × ULN; activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; prothrombin time (PT) ≤ 1.5 × ULN;

Exclusion Criteria:

(1) previous treatment history

  1. Have previously been treated with PI3K inhibitors, mTOR inhibitors (such as everolimus) or AKT inhibitors.
  2. Patients who have received targeted therapy within 4 weeks before the first dose or ≤ 5 × drug half-life (if the half-life of the drug is specified, it is calculated as 5 times the half-life, otherwise 4 weeks);
  3. Patients who have received chemotherapy, hormonal antitumor therapy, immunotherapy or major surgery within 4 weeks before the first dose.

    Note: If the previous treatment was nitrosourea or mitomycin, the treatment must be discontinued at least 6 weeks before the first study drug is administered.

  4. Patients who have received radiation therapy within 4 weeks before the first dose.
  5. Have received clinical trial drug treatment within 4 weeks before the first medication, or are receiving other clinical trial drug treatment;

(2) History of disease and surgery

  1. CNS metastases requiring current treatment or uncontrolled CNS metastases; or CNS metastases confirmed but not stable for more than 4 weeks after treatment;
  2. Patients with spinal cord compression, cancerous meningitis, or meningitis;
  3. Currently diagnosed with type I or type II diabetes or fasting blood glucose levels> 6.7 mmol / L, or HbA1c> 7%;
  4. Patients with hypertension controlled by two or more drugs, or uncontrolled hypertension (systolic blood pressure> 140 mmHg or diastolic blood pressure> 90 mmHg);
  5. Left ventricular ejection fraction (LVEF) <50%; QTcF> 450 ms for men, QTcF> 470 ms for women (QTcF is calculated using Fridericia's correction formula QTcF = QT / RR 0.33); any room with obvious clinical significance History of arrhythmia (such as ventricular tachycardia, ventricular fibrillation, torsional ventricular tachycardia or frequent ventricular premature beats, congenital prolonged QT interval syndrome).
  6. Multiple factors affecting oral medication (eg, inability to swallow, chronic diarrhea, and intestinal obstruction, etc.);
  7. Patients with a clear tendency to gastrointestinal bleeding, including the following: local active ulcer lesions and positive fecal occult blood; those with a history of melena and vomiting within 2 months before the first medication; researchers believe that digestion may occur Major bleeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04324372


Contacts
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Contact: xu jianming, PHD 010-66947178 jmxu2003@163.com

Locations
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China, China/BEIJING
The Fifth Medical Center of PLA Ceneral Hospital Recruiting
Beijing, China/BEIJING, China, 100071
Contact: XU JIANMING, phd    010-66947178    jmxu2003@163.com   
Sponsors and Collaborators
Sunshine Lake Pharma Co., Ltd.
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Responsible Party: Sunshine Lake Pharma Co., Ltd.
ClinicalTrials.gov Identifier: NCT04324372    
Other Study ID Numbers: HEC68498-P-01
First Posted: March 27, 2020    Key Record Dates
Last Update Posted: March 27, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Neoplasms