BIOmarker Driven Trial of VEGFR2 Inhibitor in Advanced or Metastatic Sarcoma

NCT04072042 | Recruiting Phase 2 DMC

• 1 other identifier: 2019LLS167
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the efficacy and safety of Apatinib monotherapy for relapsed or refractory advanced bone and soft tissue sarcoma with VEGFR-2 (KDR) 604A\>G polymorphism as predictive biomarker

Conditions

Sarcoma

Outcome Measures

Primary Outcomes (1)

• 4 month-progression free rate (PFR) in each of the 3 cohorts

  Each arm of the study is analyzed separately with the progression free rate (PFR) as the primary outome measure. PFR is defined as the proportion of patients that are progression-free according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  4 months from recruitment

Secondary Outcomes (10)

• progression free rate (PFR) in biomarker negative control in each of the 3 cohorts

  4 months from recruitment

• progression free survival(PFS) between biomarker positive and negative patients in each of the 3 cohorts

  Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 months

• Correlation of biomarker positivity with overall survival (OS)

  Baseline until death, assessed for an average of 24 months

• ORR, DCR and DOR between biomarker positive and negative patients in each of the 3 cohorts

  Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 months

• Incidence of Treatment-Emergent Adverse Events

  through study completion, an average of 8 months

Other Outcomes (4)

• Exploratory outcome: Subgroup analysis of progression-free survival(PFS)

  Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 months

• Exploratory outcome: the molecular analysis of tumor sample in each of the 3 cohorts

  through study completion, an average of 8 months

• Exploratory outcome: the pattern of disease progression between different cohorts and different sub-group within each cohort

  Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 months

Study Arms (3)

VEGFR SNP-Positive Sarcoma Arm (VEGFR-AtoG)

EXPERIMENTAL

In this arm, patients with VEGFR2-604 A\>G single nucleotide polymorphism (SNP) were recruited for the efficacy analysis. Biomarker positive patients will receive Apatinib 250mg tablet by mouth, bid. Biomarker negative patients are treated with the same regimens as a non-comparative, non-randomized, pragmatic control without a pre-specified sample size.

Drug: Apatinib monotherapy

CSF1-Positive Sarcoma Arm (CSF1-high)

EXPERIMENTAL

In this arm, patients with CSF1-positivity were recruited for the efficacy analysis. CSF1-positivity is defined as CSF1 copy number amplification and/or CSF1 expression ≥ 30% by immunohistochemistry (IHC) in the sarcoma tumor specimen according to the institutional pathological review. Biomarker positive patients will receive Apatinib 250mg tablet by mouth, bid. Biomarker negative patients are treated with the same regimens as a non-comparative, non-randomized, pragmatic control without a pre-specified sample size.

Drug: Apatinib monotherapy

4q12 amplicon-Positive Sarcoma Arm (4q12-amp)

EXPERIMENTAL

In this arm, patients with 4q12 amplicon (4q12-amp) were recruited for the efficacy analysis. 4q12-amp is defined as copy number amplification of chromosome segment 4q12 detected by fluorescence in situ hybridization (FISH) in the sarcoma tumor specimen according to the institutional pathological review. Biomarker positive patients will receive Apatinib 250mg tablet by mouth, bid. Biomarker negative patients are treated with the same regimens as a non-comparative, non-randomized, pragmatic control without a pre-specified sample size.

Drug: Apatinib monotherapy

Interventions

Apatinib monotherapy DRUG

patients will receive Apatinib 250mg tablet by mouth, bid.

Also known as: VEGFR inhibitor; Rivoceranib

4q12 amplicon-Positive Sarcoma Arm (4q12-amp); CSF1-Positive Sarcoma Arm (CSF1-high); VEGFR SNP-Positive Sarcoma Arm (VEGFR-AtoG)

Eligibility Criteria

• Age: 8 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• age between 8 and 65 years;
• diagnosis of histologically confirmed advanced bone and soft tissue sarcoma excluding adipocytic tumor;
• identification of pulmonary lesion is mandatory;
• refractory to prior treatment consisted of standard National Comprehensive Cancer Network (NCCN) guideline recommended first-line chemotherapy;
• Eastern Cooperative Oncology Group(ECOG) performance status 0-2 with a life expectancy \>3 months;
• adequate renal, hepatic, and hemopoietic function;normal or controlled blood pressure;
• advanced stage that complete surgical resection of all lesions are infeasible;
• no serious thoracic comorbidities with adequate pulmonary function for daily living;
• previously treated with tyrosine kinase inhibitors (TKIs) for less than 8 weeks but off treatment due to manageable complications such as wound complications or pneumothorax without adequate interventions. The complications is resolved and disappeared at enrollment.

You may not qualify if:

• have had other kinds of malignant tumors at the same time;
• cardiac insufficiency or arrhythmia;
• uncontrolled complications, such as diabetes mellitus and so on;
• coagulation disorders or Hemorrhagic diseases ;
• pleural or peritoneal effusion that needs to be handled by surgical treatment;
• combined with other infections or wound complications;
• wound dystrophy, poor soft-tissue around implantation risky of non-healing given angiogenesis inhibitor at baseline;
• previously treated with VEGFR TKIs for more than 8 weeks
• previous treated with VEGFR TKIs but off treatment due to oncological assessment or dose-limiting complications given adequate interventions.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

apatinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Weibin Zhang

  Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weibin Zhang, PhD, MD

CONTACT

+8613501824630; zhangweibin10368@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Radiological Assessment of tumor will be independently reviewed by outcome assessor, who is blinded to patient biomarker status
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the orthopaedics department

Model Details: In each of the treatment arm, we recruit patients according to the biomarker status and hypothesize that the anti-angiogenic therapeutic efficay would be higher than historical control as a biomarker-driven approach.

Study Record Dates

• First Submitted: August 25, 2019
• First Posted: August 28, 2019
• Study Start: October 30, 2019
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 14, 2025

Record last verified: 2025-05

Locations

CN (1)