Anlotinib Hydrochloride Versus Imatinib Mesylate in Locally Advanced, Unresectable or Metastatic Chordoma (CSSG-03)

A Prospective, Multicentre, Open-label, Randomised Phase 2 Trial to Study the Efficacy and Safety of Anlotinib Hydrochloride Versus Imatinib Mesylate in Locally Advanced, Unresectable or Metastatic Chordoma

For local relapse not amenable to reasonable curative surgery or for those with metastatic chordoma, chemotherapy is recognised as inactive. The major study drug is the small molecular tyrosine kinase inhibitors targeted at the stem cell factor receptor (KIT) and the platelet-derived growth factor receptors (PDGFRA and PDGFRB), eg. imatinib. Anlotinib is a novel tyrosine kinase inhibitor targeting both at VEGFR-2, -3 and PDGFRA and PDGFRB with high affinity, which also showed broad antitumor activity against EGFR and so on. Thus this multicenter, two-armed phase II trial of PKUPH-sarcoma 05 intended to investigate the efficacy and safety of anlotinib versus imatinib on advanced chordoma.

Study Overview

• Status: Unknown
• Conditions: Quality of Life; Advanced Cancer; Chordoma; Effect of Drugs
• Intervention / Treatment: Drug: Anlotinib Hydrochloride

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lu Xie, M.D.; Phone Number: +8613401044719; Email: xie.lu@hotmail.com
• Study Contact Backup: Name: Jie Xu, M.D.; Phone Number: +8615901040835; Email: xujie_pkuph@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Tingting Ren, Ph. D.; Phone Number: +861380095026; Email: tumorcenter@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18 years and older;
• histologically proven metastatic or locally advanced chordoma, reviewed by the Pathology Committee of Peking University People's Hospital;
• not amenable to curative-intent surgery;
• measurable with computed tomography scan or magnetic resonance imaging, per RECIST, version 1.1.

Exclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG)30 performance status more than 2 ;
• life expectancy less than 12 weeks;
• with severe or uncontrolled medical disorders (≥grade 2 of Common Terminology Criteria for Adverse Events version 4.03 [CTCAE version 4.03]) that could jeopardise the outcomes of the study, for example, cardiac clinical symptom or disease with LVEF (left ventricular ejection fraction) <50%, hypertension that could not be well controlled through antihypertensive drugs and so on;
• weight loss of 20% or more before illness;
• brain or leptomeningeal metastasis;
• surgical procedure or radiotherapy within 4 weeks of enrollment;
• active gastroduodenal ulcer, previous condition associated with risk of bleeding or requiring anticoagulation;
• proteinuria or hematuria;
• denutrition with albuminemia less than 25 g/L;
• pregnant or breastfeeding status;
• other malignancy, positive HBV/HCV/HIV serology;
• known allergy to the experimental agents;
• had ever used anti-angiogenesis TKIs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: anlotinib arm; anlotinib was given at a fixed dose of 12mg D1-14 every 21 days	Drug: Anlotinib Hydrochloride; anlotinib was given at a fixed dose of 12mg D1-14 every 21 days
Active Comparator: Arm B: imatinib arm; Imatinib was given at dose of 400 mg twice daily continuously	Drug: Anlotinib Hydrochloride; anlotinib was given at a fixed dose of 12mg D1-14 every 21 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate, ORR	CR+PR in the intent-to-treat population according to RECIST, version 1.1	6 months
Progression-free Survival, PFS	Progression-free survival is defined as time from randomisation to the first occurrence of progression of disease or death from any cause within 63 days of last response assessment or randomisation	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival, OS	OS is defined as time from randomisation to the first occurrence of death from any cause within 63 days of last response assessment or randomisation.	5 years

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Peking University First Hospital; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Chinese PLA General Hospital; Peking University Third Hospital; Peking University Cancer Hospital & Institute; Peking University Shougang Hospital; Beijing Jishuitan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2019
• Primary Completion (Anticipated): October 30, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: July 31, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (Actual): August 2, 2019

Study Record Updates

• Last Update Posted (Actual): August 5, 2019
• Last Update Submitted That Met QC Criteria: August 1, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: quality of life; survival; anlotinib; unresectable; imatinib; chordoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Chordoma
• Other Study ID Numbers: PKUPH-sarcoma 05

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