| Eligibility |
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, Please refer to attachment 7 for details.
- 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(Except for advanced thyroid cancer).
- No immunodeficiency.
- 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:
-Within 4 weeks before the first use of the study drug, the patient received anti- tumor
drug therapy such as chemotherapy, targeted therapy, radiotherapy, biological therapy or
endocrine therapy, except for the following: Nitrous urea or mitomycin C were used within 6
weeks before the first use of the study drug; Oral fluorouracil and small molecular
targeted drugs were used within 2 weeks before the first use of the study drug or within 5
half-lives (whichever is the longer); Chinese medicine with anti-cancer indications was
used within 1 week before the first use of the study drug.
- Surgical treatment (except biopsy) was performed within 4 weeks before the first use
of study drug.
- 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 received 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.
- Patients with active pulmonary disease, interstitial pneumonia or pulmonary fibrosis.
- 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 CYP3A 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 (such as serious mental, neurological,
cardiovascular, respiratory and other system diseases) or active infection that
significantly affects clinical trials.
- The patient has clinical symptoms or uncontrolled central nervous system metastasis or
meningeal metastasis, which is judged by the investigator to be unsuitable for
admission;
- 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? diarrhea,
etc..
- Positive results of HIV or Treponema pallidum antibodies (Acceptance of Treponema
pallidum antibody titer test results in a Class III Grade I hospital including
research centers).
- 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 progressed after using a receptor tyrosine kinase inhibitor that
targets VEGFR.
- Investigators consider that it is not appropriate for subjects to participate in this
study from the perspective of clinical treatment.
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