Inclusion Criteria
1. Written informed consent provided before any study-specific procedures are initiated. Subject must be able to understand and be willing to sign a written informed consent form.
2. Male or female at least 18 years of age.
3. a. Indication A - ASPS: Histologically proven, unresectable, locally advanced or metastatic alveolar soft part sarcoma. b. CLOSED Indication B - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular origin and of the bone). c. CLOSED Indication C - SS: Histologically proven, unresectable, recurrent, locally advanced or metastatic synovial sarcoma. d. CLOSED Indication D - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, and vascular origin).
3\. Open Indication E: Any sarcomas or other solid tumors 4. a. Indication A - ASPS: Subjects with or without prior therapy. b. Indications B - LMS: Subjects previously treated with at least one prior line of approved therapy. (New Recruitment Suspended) c. Indication C - SS: Subjects previously treated with at least one prior line of standard systemic therapy, including first-line anthracycline containing regimen (except if medically contraindicated or refused by subject). d. Indication D - LMS: Treatment of patients with metastatic or advanced leiomyosarcoma (LMS) who have failed at least one prior line of standard therapy and are ineligible for or refuse standard second-line therapy or are suitable for third- and further-line treatment. Patients must have received and progressed on prior therapy and have been treated any line with an anthracycline. e. Indication E: Any sarcomas or other solid tumors such as NSCLC, SCLC and Thyroid cancer etc.: Subjects exhausted SOC treatment or refuse for any SOC treatment.
5\. Show clinical or objective disease progression after the last administration of the last standard therapy or have stopped standard therapy due to intolerability within 6 months of enrollment (excluding ASPS subjects who have not received prior therapy).
6\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by CT or MRI scan of the chest, abdomen and pelvis (and other areas of disease) within 28 days prior to enrollment. 8. Life expectancy of at least 3 months.
9\. Females of childbearing potential must have a negative pregnancy test (by serum beta- HCG) within 7 days prior to the start of treatment.
10\. Female of childbearing potential must be surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the investigator), or agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 2 years. Males must agree to use adequate contraception since signing of the informed consent form until at least 3 months after the last study drug administration. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) at the discretion of the investigator. 11. Adequate hematologic, hepatic and renal function as assessed by the following laboratory requirements conducted within 28 days of enrollment:
a. Total bilirubin \< the upper limit of normal (ULN), unless the patient has documented Gilbert's disease for which the total bilirubin should be \< 3. b. Alanine aminotransferase and aspartate aminotransferase \< 2.5 of the ULN (\< 5 x of ULN for subjects with liver involvement of their cancer) c. Amylase and lipase \< 1.5 x of ULN d. Serum creatinine \< 1.5 x of ULN e. Glomerular filtration rate \> 30ml/min/1.73 m2 according to the Modified Diet in Renal Disease abbreviated formula or creatinine clearance (CrCL) \> 60 ml/min (Cockcroft and Gault) or by 24 hour urine collection. f. International normalize ratio (INR) and the activated partial thromboplastin time (aPTT/PTT) \< 1.5 x ULN. (Subjects who are therapeutically treated with an agent such LMWH or heparin will be allowed to participate provided that no prior evidence of an underlying abnormality in coagulation parameters exists) g. Platelet count \> 100,000 cells/mm3, hemoglobin \> 9 g/dL, absolute neutrophil count \> 1,500 cells/mm3 h. Alkaline phosphatase limit \<2.5 x ULN (\<5 x ULN for subjects with liver involvement of their cancer) i. Urine protein \< 30 mg/dL. If urine protein is \> 30 mg/dL, a 24-hour urine collection will be required and must show total protein excretion \<1,000 mg per 24 hours or spot urine protein (mg/dL) to creatinine (mg/dL) ratio must be \<1.0.
12\. Left ventricular ejection fraction (LVEF) of \> 50% by ECHO or MUGA within 56 days of enrollment. 13. Two readings of systolic blood pressure \< 140 mm Hg and diastolic blood pressure \< 90 mm Hg at screening taken at least 5 minutes apart in the sitting position after 5 minutes of rest. Subjects with well managed hypertension who are on oral antihypertensives must be on their current medication(s) and stable dose(s) for at least 2 weeks prior to enrollment.
Exclusion Criteria
1. Prior treatment with or have known hypersensitivity to AL3818.
2. a. Indication A - ASPS: Prior treatment with cediranib. b. Indication B - LMS: Prior treatment with or have known hypersensitivity to dacarbazine. (New Recruitment Suspended) c. Indication C - SS: Prior treatment with or have known hypersensitivity to dacarbazine.
d. Indication D - LMS: Prior treatment with anlotinib.
3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS, LMS, or SS within 5 years before enrollment except for successfully treated in situ carcinoma, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and T1).
4. Received last dose of systemic cytotoxic therapy or investigational therapy within 21 days of enrollment or last dose of hormonal therapy, immunotherapy, targeted therapy or any other type of non-cytotoxic anti-cancer therapy within 14 days of enrollment.
5. Prior treatment with extended-field radiotherapy (EFRT) within 28 days of enrollment or prior treatment with any other form of radiotherapy within 14 days of enrollment.
6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided that they are stable with no evidence of progression by imaging, and all neurologic symptoms have returned to baseline, and should not be using corticosteroids for at least 7 days prior to study treatment.
7. Cavitary tumors or tumors invading or abutting large blood vessels in the thorax.
8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess within 6 months of enrollment.
9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).
10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and hemoptysis within 6 months prior to enrollment.
11. CTCAE version 4.03 \> grade 2 pulmonary hemorrhage or \> grade 3 of other forms of bleeding within 28 days prior to enrollment.
12. History of untreated deep venous thrombosis (DVT) within the past 6 months. Patients with recent DVT who are treated with therapeutic anti-coagulating agents (excluding therapeutic warfarin which is exclusionary) for at least 14 days prior to start of study treatment.
13. Use of aspirin (\>325 mg/day) within 10 days prior to the first dose of study treatment.
The use of prophylactic therapeutic anti-coagulants are allowed provided that INR or aPTT are within therapeutic limits (according to the medical standard of the enrollment institution) and patient has been on a stable dose of anticoagulants for at least two weeks prior to the first dose of study treatment.
14. Serious non-healing wound, active ulcer.
15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment or minor surgical procedure within 7 days of enrollment.
16. CTCAE version 4.03 \> grade 3 peripheral neuropathy
17. Any unrecovered toxicity reactions of CTCAE version 4.03 \> grade 1 caused by any previous therapy (excluding alopecia and neurotoxicity \< grade 2)
18. QTcF \> 470 msec (per Fridericia's formula) on electrocardiogram within 28 days of enrollment.
19. Severe and uncontrolled disease, including:
1. Class I and above myocardial ischemia or myocardial infarction, cardiac arrhythmia and Class 2 or above congestive heart failure classified according to New York Heart Association (NYHA)
2. Active or failed to control serious infections (CTCAE version 4.03 \> grade 2 infections)
3. Liver disease such as cirrhosis of the liver, decompensated liver disease, chronic active hepatitis needing anti-viral therapy
4. Renal failure needing hemodialysis or peritoneal dialysis
5. Poorly controlled diabetes (HgA1C \>8)
6. Untreated and uncontrolled epileptic seizures
7. History of psychotropic drug abuse and inability to quit
8. Untreated psychiatric disorders
20. Known HIV-positive
21. Had organ transplantation
22. Clinical conditions affecting the intake and use of oral medications (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction)
23. Females who are pregnant or are breast-feeding.
24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5; or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and CYP2C19; or QT prolongating medications within 14 days prior to enrollment and during the study unless there was an emergent or life-threatening medical condition that required it.
25. Any medical intervention, condition or any other circumstance which in the opinion of the investigator or the sponsor's medical monitor, could compromise adherence to study procedures or study objectives.
