Apatinib for Advanced Soft Tissue Sarcoma Patients: a Phase 2, Multicenter Trial

NCT03104335 | Withdrawn Phase 2 DMC

• 1 other identifier: PekingUAH-sarcoma070330
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

Patients with advanced soft tissue sarcoma(rhabdomyosarcoma and liposarcoma excluded), who experience progression after standard chemotherapy, have limited treatment options which promise a survival benefit.This trial tends to explore apatinib, which is a domestic highly selective inhibitor of vascular endothelial growth factor receptor-2, as a treatment option for heavily pretreated soft tissue sarcoma patients.

Conditions

Soft Tissue Sarcoma Adult; Advanced Cancer

Keywords

soft tissue sarcoma; advanced; apatinib; tyrosine-kinase inhibitors

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  the number of participats (complete response+ partial response according to RECIST 1.1)/ total participants number

  4 months

Secondary Outcomes (3)

• Duration of Response (DR)

  4 months and 6 months

• Progression-Free Survival(PFS)

  6 months

• Overall Survival(OS)

  12 months

Study Arms (1)

Study arm

EXPERIMENTAL

every participant will recieve 750 mg daily once oral administration of apatinib for body surface area (BSA) \> 1.5 and 500mg daily for BSA \<1.5. Half an hour after meal and everyday at the same time is usually advised.

Drug: Apatinib

Interventions

Apatinib DRUG

750 mg daily once oral administration of apatinib for body surface area (BSA) \> 1.5 and 500mg daily for BSA \<1.5. Half an hour after meal and everyday at the same time is usually advised.

Also known as: apatinib mesylate tablets

Study arm

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a histologically and/or cytologically confirmed soft tissue sarcoma(rhabdomyosarcoma and liposarcoma excluded) who are resistant / refractory to approved therapies or for whom no curative therapies are available.
• All previous treatment (including surgery, radiotherapy and systemic anti-neoplastic therapy) must have been completed at least three weeks prior to study entry and any acute toxicities must have resolved.
• Aged \>/= 16 years.
• Eastern Cooperative Oncology Group (ECOG) performance status score of \</= 2.
• Written informed consent prior to any study specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
• Willing and able to comply with the protocol guidelines for the duration of the study.

You may not qualify if:

• Unstable metastases to the central nervous system (CNS).
• tumor embolus located at pulmonary vein.
• Any of the following laboratory parameters: a) hemoglobin \< 9 g/dL (5.6 mmol/L); b) neutrophils \<1.5 x 109/L; c) platelets \<100 x 109/L; d) serum bilirubin \>25 µmol/L (1.5 mg/dL); e) liver function tests with values \>3 x upper limit of normal (ULN) f) serum creatinine \>1.5 x ULN or creatinine clearance \< 60 mL/minute.
• Positive history of HIV, active hepatitis B or active hepatitis C or severe/uncontrolled intercurrent illness or infection
• Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start
• Patients with marked Baseline prolongation of QT/QTc interval (QTc interval \> 450 msec for males or \> 470 msec for females) using the Fridericia method for QTc analysis
• Requirement for chronic use of full dose aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
• Poorly controlled hypertension (defined as requiring changes in any hypertensive regimen within 1 week of study entry) or patients diagnosed with hypertension based on repeat blood pressure measurements of \>160/90 mmHg at Screening
• Proteinuria \> 1+ on urine dipstick testing or 30 mg/dL
• A history of gastrointestinal malabsorption or having undergone surgery requiring gastrointestinal anastomoses within four weeks of starting therapy or who have not recovered from major surgery within three weeks of starting therapy History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the Investigator, would impair study compliance.
• Any treatment with investigational drugs within 30 days before the start of the study
• Previous treatment with apatinib or other anti-angiogenesis tyrosine kinase inhibitors
• receive CYP3A4 inhibitors within 7 days or CYP3A4 inducers within 12 days.
• uncontrollable complicated diseases: such as infectious diseases, diabetes mellitus and so on.
• Women who are pregnant or breast-feeding; women of childbearing potential with a positive pregnancy test at Screening or no pregnancy test. Women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception (including two forms of contraception, one of which must be a barrier method) in the opinion of the Investigator. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Peking University Shougang Hospital: collaborator
• Peking University International Hospital: collaborator

Study Sites (3)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

Peking University Shougang Hospital

Beijing, Beijing Municipality, 100144, China

Location

Peking University International Hospital

Beijing, Beijing Municipality, 102206, China

Location

Related Publications (12)

• Jo VY, Doyle LA. Refinements in Sarcoma Classification in the Current 2013 World Health Organization Classification of Tumours of Soft Tissue and Bone. Surg Oncol Clin N Am. 2016 Oct;25(4):621-43. doi: 10.1016/j.soc.2016.05.001. Epub 2016 Jul 30.

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• Brodowicz T, Liegl-Atzwager B, Tresch E, Taieb S, Kramar A, Gruenwald V, Vanseymortier M, Clisant S, Blay JY, Le Cesne A, Penel N. Study protocol of REGOSARC trial: activity and safety of regorafenib in advanced soft tissue sarcoma: a multinational, randomized, placebo-controlled, phase II trial. BMC Cancer. 2015 Mar 14;15:127. doi: 10.1186/s12885-015-1143-y.

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• Bains R, Magdum A, Bhat W, Roy A, Platt A, Stanley P. Soft tissue sarcoma - A review of presentation, management and outcomes in 110 patients. Surgeon. 2016 Jun;14(3):129-35. doi: 10.1016/j.surge.2014.06.002. Epub 2014 Sep 30.

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• Sleijfer S, Ray-Coquard I, Papai Z, Le Cesne A, Scurr M, Schoffski P, Collin F, Pandite L, Marreaud S, De Brauwer A, van Glabbeke M, Verweij J, Blay JY. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol. 2009 Jul 1;27(19):3126-32. doi: 10.1200/JCO.2008.21.3223. Epub 2009 May 18.

  PMID: 19451427 BACKGROUND

• van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schoffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. doi: 10.1016/S0140-6736(12)60651-5. Epub 2012 May 16.

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• Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. doi: 10.1016/S0140-6736(16)30587-6. Epub 2016 Jun 9.

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• Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol. 2016 May 1;34(13):1448-54. doi: 10.1200/JCO.2015.63.5995. Epub 2016 Feb 16.

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• Li J, Qin S, Xu J, Guo W, Xiong J, Bai Y, Sun G, Yang Y, Wang L, Xu N, Cheng Y, Wang Z, Zheng L, Tao M, Zhu X, Ji D, Liu X, Yu H. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer: results from a randomized, placebo-controlled, parallel-arm, phase II trial. J Clin Oncol. 2013 Sep 10;31(26):3219-25. doi: 10.1200/JCO.2013.48.8585. Epub 2013 Aug 5.

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• Li J, Zhao X, Chen L, Guo H, Lv F, Jia K, Yv K, Wang F, Li C, Qian J, Zheng C, Zuo Y. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer. 2010 Oct 5;10:529. doi: 10.1186/1471-2407-10-529.

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• Cirillo M, Venturini M, Ciccarelli L, Coati F, Bortolami O, Verlato G. Clinician versus nurse symptom reporting using the National Cancer Institute-Common Terminology Criteria for Adverse Events during chemotherapy: results of a comparison based on patient's self-reported questionnaire. Ann Oncol. 2009 Dec;20(12):1929-35. doi: 10.1093/annonc/mdp287. Epub 2009 Jul 17.

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MeSH Terms

Conditions

Sarcoma

Interventions

apatinib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Wei Guo, M.D.Ph.D.

  Musculoskeletal Tumor Center of Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Musculoskeletal Tumor Center and Principal Investigator of this study

Model Details: participants will be advised to recieve 750 mg daily once apatinib for body surface area (BSA) \> 1.5 and 500mg daily for BSA \<1.5. Half an hour after meal and everyday at the same time is usually advised.

Study Record Dates

• First Submitted: April 2, 2017
• First Posted: April 7, 2017
• Study Start: April 1, 2017
• Primary Completion: June 30, 2019
• Study Completion: March 1, 2020
• Last Updated: May 19, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)