Mesylate Apatinib for Stage Ⅳ STS After Failure of Chemotherapy

Mesylate Apatinib for Stage Ⅳ Soft Tissue Sarcoma Patients After Failure of Traditional Chemotherapy: Prospective, Open-label, Single-Arm, Multi-center Phase II Clinical Trial

This is a Prospective, Open-label, Single-Arm, Multi-center phase II clinical trial evaluating the efficacy and safety of Apatinib for Chemotherapy Failure Ⅳ Stage Soft Tissue Sarcoma.

Study Overview

• Status: Unknown
• Conditions: Soft Tissue Sarcoma, Adult, Stage II
• Intervention / Treatment: Drug: Apatinib

Detailed Description

The prognosis of sarcoma patients in stage IV is poor. For STS, the response rate of chemotherapy is only 20-35% and the median survival time is about 12 months. The 5 year survival rate is lower than 10% reported in several large-scale studies. Although chemotherapy plays a major role in the treatment of advanced STS, the classic chemotherapy agents are not curative. Combination chemotherapy or dose-dense regimens have largely failed to improve the response rates. Long-term using of cytotoxic drugs increased the risk of toxicity in patients. Apatinib is a small molecular inhibitor of Vascular Epithelial Growth Factor Receptor-2 (VEGFR-2). It has been approved as a second-line treatment for advanced gastric cancer. Several phase III clinical studies of non small cell lung cancer, liver cancer, colorectal cancer and other tumors also showed apatinib has less toxic side effects and better patient tolerance. However, the clinical application of apatinib in STS is still lack of evidence-based medicine. And this clinical trial is designed to prospectively investigate the efficacy and safety of apatinib in stage IV sarcoma patients who failed in chemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jilong Yang, M.D., Ph.D.; Phone Number: +8618622221626; Email: yangjilong@tjmuch.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Hospital & Institute
      • Contact: Jilong Yang, M.D., Ph.D.; Phone Number: +8618622221626; Email: yangjilong@tjmuch.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients voluntarily join the study, signed informed consent, good compliance;
• The pathology was diagnosed as stage Ⅳ soft tissue sarcoma patients, clinical staging using the American Cancer Research Joint Committee (AJCC) TNM staging criteria. According to CT or MRI at least one measurable lesion;
• At least one chemotherapy regimen (containing anthracycline) was treated and evaluated as "disease progression" in terms of the efficacy evaluation criteria of solid tumors (RECIST 1.1).
• 18 to 70 years old, PS score: 0 ~ 2; expected survival period of more than 3 months;
• The laboratory check meets the following criteria:
• Blood routine examination: HB ≥ 100g / L (14 days without blood transfusion); ANC ≥ 1.5 × 109 / L; PLT ≥ 80 × 109 / L
• Biochemical tests: serum creatinine Cr ≤ normal upper limit (ULN), bilirubin BIL ≤ normal upper limit (ULN), ALT, AST ≤ 1.5 × normal upper limit (ULN), for liver metastases ≤ 5 × normal upper limit (ULN); fasting triglyceride ≤ 3.0mmol / L, fasting cholesterol ≤ 7.75mmol / L;
• Doppler ultrasonography: left ventricular ejection fraction (LVEF) ≥ normal low (50%).
• Women should agree that contraceptive measures (such as IUDs, contraceptives or condoms) must be used within six months of the study period and after the end of the study; serum or urine pregnancy studies were negative for 7 days prior to study , and must be non-lactating patients; men should agree that contraceptive measures must be used within six months of the study period and after the end of the study period.

Exclusion Criteria:

• Patients who have received antiangiogenic therapy or other targeted treatment for no more than 3 months, such as Endostar, Erlotinib, Sunitinib, Sorafenib, Avastin, Imatinib, Famitinib, Pazopanib and other drugs.
• Past or concurrent with other malignancies, except for cured skin basal cell carcinoma and cervical in situ cancer;
• Participated in other drug clinical researchers within four weeks;
• Previously received anticancer treatment patients with NCI CTC AE grade> 1 grade toxicity;
• Have a variety of factors that affect oral medication (such as can not swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.)
• Known brain metastases, spinal cord compression, cancerous meningitis, or screening when the CT or MRI examination found that the brain or pia mater disease;
• Patients with any severe and / or uncontrolled disease, for example:
• Unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months prior to randomization, severe uncontrollable arrhythmia; poor blood pressure control (systolic blood pressure> 140 mmHg, diastolic blood pressure> 90 mmHg )patient;
• Active or uncontrollable serious infection;
• Liver diseases such as cirrhosis, decompensated liver disease, chronic active hepatitis;
• Poor control of diabetes (fasting blood glucose (FBG)> 10mmol / L);
• Urinary routine urinary protein ≥ ++, and confirmed 24 hours urine protein> 1.0 g;
• Long untreated wound or fracture;
• Patients with bleeding tendency (such as active gastrointestinal ulcers) or treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or analogues;
• Interventional venous thrombosis events such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, and pulmonary embolism before the first medication.
• Have a history of psychiatric abuse and can not quit or have mental disorders;
• Have a history of immunodeficiency, including HIV testing positive or other acquired, congenital immune deficiency disease, or a history of organ transplantation;
• According to the researcher's judgment, there are serious illnesses that compromise the patient's safety or affect the patient's completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: apatinib group; apatinib 500mg po qd, 28 days for a cycle.	Drug: Apatinib; Apatinib 500 mg is administered orally daily, until disease progression or untolerable toxicity.; Other Names: Apatinib Mesylate Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS is defined as the length of time from random assignment to disease progression or to death resulting from any cause other than the progress.	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate(DCR）	Investigators will assess treatment response according to Response Evaluation Criteria in Solid Tumors 1.1（RECIST1.1）	2 year
Objective tumor response rate(ORR)	ORR is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as best overall response according to radiological assessments.	2 year
Overall survival(OS)	OS is defined as the length of time from random assignment to death or to last contact.	3 year
Adverse Events(AEs)	AEs are evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.	2 year

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Collaborators: Zhejiang Cancer Hospital; Fudan University; Liaoning Tumor Hospital & Institute; Gansu Cancer Hospital
• Investigators: Study Chair: Jilong Yang, M.D., Ph.D., Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Anticipated): November 1, 2018
• Study Completion (Anticipated): May 1, 2019

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 17, 2017
• First Posted (Actual): April 20, 2017

Study Record Updates

• Last Update Posted (Actual): May 22, 2017
• Last Update Submitted That Met QC Criteria: May 19, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Apatinib; Soft Tissue Sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: S201602

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No