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Study of Challenge Meditech 082 (CM082) Tablets in Patients With Advanced Malignant 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. Identifier: NCT03792958
Recruitment Status : Not yet recruiting
First Posted : January 4, 2019
Last Update Posted : January 4, 2019
Shanghai East Hospital
Information provided by (Responsible Party):

Brief Summary:
This is a Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Oral Dosing of CM082 tablets in Chinese Patients With Advanced Malignant Solid Tumors

Condition or disease Intervention/treatment Phase
Advanced Malignant Solid Tumors Drug: CM082 Phase 1

Detailed Description:
This is a single-center、open-label and non-controlled Phase 1 study which will be conducted in two parts: part A is the dose-escalation phase; part B is dose-expansion phase. The dose-escalation phase is guided by pharmacokinetics (PK) and safety, according to the standard 3+3 dose-escalation schema. CM082 tablets are taken orally with a starting dose of 200 mg and a subsequent dose of 400, 600 and 800 mg. The way of administration is as follows: QD or BID. The primary objective of this study is to determine the maximum tolerable dose (MTD)、characteristics of dose-limited toxicity (DLT) and pharmacokinetics (PK). Secondary objectives include safety、tolerability and preliminary efficacy

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Sequential Assignment
Intervention Model Description: The initial dose is set at 200 mg, followed by 400 mg, 600 mg and 800 mg for dose increment.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of CM082 Tablets in the Treatment of Advanced Malignant Solid Tumors: Safety, Tolerance and Pharmacokinetics
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Arm Intervention/treatment
Experimental: CM082
CM082 tablet
Drug: CM082
CM082 tablets taken orally 200、400、600 and 800 mg (QD or BID)
Other Name: X-82

Primary Outcome Measures :
  1. Maximum tolerable dose (MTD) or dose to absorb saturation [ Time Frame: From the first dose to the 28th day of administration ]
  2. Dose-Limiting Toxicity [ Time Frame: From the first dose to the 28th day of administration ]
    Characteristics of dose-limiting toxicity (DLT), evaluation criteria: National Cancer Institute (NCI) CTC classification (version 4.03)

  3. Pharmacokinetic parameters [ Time Frame: From the first dose to the 28th day of administration ]
    Peak concentration

  4. Pharmacokinetic parameters [ Time Frame: From the first dose to the 28th day of administration ]
    Area under the time curve of blood concentration from 0 h to the last time of blood collection

  5. Pharmacokinetic parameters [ Time Frame: From the first dose to the 28th day of administration ]
    0 to Infinite Area under Blood Drug Concentration Curve

  6. Pharmacokinetic parameters [ Time Frame: From the first dose to the 28th day of administration ]
    Peak time

  7. Pharmacokinetic parameters [ Time Frame: From the first dose to the 28th day of administration ]
    Apparent terminal elimination half-life

  8. Pharmacokinetic parameters [ Time Frame: From the first dose to the 28th day of administration ]
    Terminal elimination rate constant

Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: 12 months ]
  2. Disease control rate [ Time Frame: 12 months ]
  3. Progression-free survival [ Time Frame: 12 months ]
  4. Overall survival [ Time Frame: 36 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age:≥18 years.
  • BMI generally ranges from 18-28 (BMI=Weight (Kg)/Height (m)2)
  • Patients with advanced malignant solid tumors confirmed by histological or cytological examination.
  • According to Recist1.1 criteria, patients have measurable or assessable tumors, and patients with advanced malignant solid tumors who have failed to respond to previous standard treatment regimens, are unable to tolerate previous treatment regimens or lack effective treatment regimens.
  • Organ function level must meet the following requirements (7 days before treatment):

    • Bone marrow: absolute neutrophil count (ANC)≥1.5^109/L, platelet (PLT)≥100^109/L, hemoglobin (HB)≥9g/dL (no blood transfusion or component blood received within 14 days before detection).
    • Liver: Serum bilirubin (TBIL) ≤1.5 * upper limit of normal (ULN) , aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 * ULN (If the patient's liver metastases, AST and ALT are allowed to be ≤ 5 * ULN) ).
    • Serum creatinine≤1.5 * ULN and endogenous creatinine clearance rate≥50mL/min. According to Cockcroft-Gault formula, creatinine clearance (CrCl)=[(140-Age)*body weight (kg)* (0.85, female only)]/(72*serum creatinine)].
    • International normalized ratio (INR) and activated partial thromboplastin time (APTT)≤1.5 * ULN (This provision applies only to patients who do not receive anticoagulant treatment; for patients receiving anticoagulant treatment, anticoagulants should be used within the treatment requirements).
    • Urine protein (UP)≤1+. If UP>1+, 24-hour UP should be collected for determination, and the total amount of UP should be ≤1g.
    • FT3、FT4 and thyroid-stimulating hormone (TSH) are normal or abnormal without clinical significance.
  • No immunodeficiency.
  • After the last antineoplastic treatment (e.g., Chemotherapy, Targeted Therapy, Radiotherapy, Biotherapy or Endocrine Therapy), the elution period is at least more than 5 half-life, up to 4 weeks;Surgical treatment for more than 3 months;The damage causes by other treatments is restored to 1 grade (CTCAE version 4.03), except for hair loss and pigmentation; If the nutritional status is stable, the long-term toxicity that cannot be recovered is allowed to exist by the investigator'judgement.
  • Expected survival time≥ 3 months.
  • Eastern Cooperative Group (ECOG) Performance Status score of ≤1.
  • The results of serum pregnancy test for women of childbearing age should be negative within 7 days before treatment.
  • Men who are fertile or women who are likely to become pregnant must use highly effective contraceptive methods (e.g., oral contraceptives, intrauterine contraceptives, sex control or barrier contraceptives combined with spermicides ) throughout the trial and continue to use contraception for 12 months after the end of treatment.
  • Patients can voluntarily sign written informed consent.

Exclusion Criteria:

  • Patients who have participated in or are participating in any other drug/therapy clinical trial (including but not limited to the anti-tumor clinical trial) within 4 weeks before treatment, counting from the time of last administration of the last clinical trial.
  • Patients who receive hematopoietic stimulating factors (e.g., granulocyte colony stimulating factor (G-CSF), erythropoietin, etc.) within one week before treatment.
  • Pleural or ascites with clinical symptoms and requiring symptomatic treatment.
  • Active pulmonary disease or previous history of pulmonary disease (e.g., interstitial pneumonia, pneumonia, obstructive pulmonary disease, asthma).
  • Having any uncontrollable clinical problems or associated risk factors, including but not limited to:

    • Poorly controlled hypertension (blood pressure persistently greater than 150/90 mmHg).
    • Left ventricular ejection fraction (LVEF)≤50%.
    • The QT interval of heart rate correction (QTc) > 450 msec (males) or 460 msec (females) ( Bazett's correction (QTcB)=QT/(RR^0.5)).
    • Patients have a clinically significant history of arrhythmia or current evidence of arrhythmia, but control of atrial fibrillation for more than 30 days before administration does not affect inclusion.
    • Patients implanted with cardiac defibrillator.
    • Poorly controlled diabetes [(fasting blood glucose should not be greater than 8.9 mmol/L after drug control) refer to CTCAE version 4.03-grade 1 of hyperglycemia].
    • Heart disease (Class III/IV congestive heart failure or cardiac block defined by the New York Heart Association).
    • Decompensated cirrhosis.
    • The following conditions occur within 6 months before treatment:

      • Deep venous thrombosis or pulmonary embolism.
      • Myocardial infarction.
      • Severe or unstable arrhythmia or angina pectoris.
      • Percutaneous Coronary Intervention, Acute Coronary Syndrome, Coronary Artery Bypass Transplantation.
      • Cerebrovascular accident, transient ischemic attack or resting limping of lower limbs.
  • Patients have not yet fully recovered from previous operations.
  • Patients who have taken strong inhibitors and inducers of CYP3A4 hepatic metabolic enzymes within 2 weeks before treatment.
  • Patients also take drugs that are at risk of prolonging QTc and/or Tdp.
  • Patients with a history of allergy to CM082 similar drugs (e.g., sunitinib, sorafenib, pazopanib, etc.).
  • Pregnant or lactating women.
  • Women/men with fertility who refuse to use contraception during the trial.
  • Any uncontrollable clinical problem or active infection that significantly affects clinical trials.
  • Patients with brain or meningeal metastases.
  • Patients with active upper gastrointestinal ulcer or other diseases known to affect drug absorption, distribution, metabolism or clearance.
  • Patients with obvious abnormal gastrointestinal function such as vomiting and diarrhea.
  • Positive results of HIV or Treponema pallidum antibodies.
  • Patients with active hepatitis B or C:

    • HBsAg or HBcAb are positive, and hepatitis B virus (HBV) DNA is detected (the results are higher than the upper limit of the normal range of the research center).
    • Hepatitis C virus (HCV) antibody test results are positive, and HCV RNA is detected (the results are higher than the upper limit of the normal range of the research center).
  • Patients who have been evaluated for progression for the first time after use of vascular endothelial growth factor drugs ( only for extended group).
  • Investigators consider that it is not appropriate for subjects to participate in this study from the perspective of clinical treatment.

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 identifier (NCT number): NCT03792958

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Contact: Guo Ye, M.D 13501678472

Sponsors and Collaborators
Shanghai East Hospital
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Principal Investigator: Li Jin, M.D Shanghai East Hospital

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Responsible Party: AnewPharma Identifier: NCT03792958     History of Changes
Other Study ID Numbers: CM082-CA-I-105
First Posted: January 4, 2019    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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