Progression-free SurvivalPhase 2APFAONCT03359018
Apatinib Plus Anti-PD1 Therapy for Advanced Osteosarcoma
A Phase 2 study testing Apatinib and SHR-1210 in people with Progression-free Survival and Overall Survival, run by Peking University People's Hospital at 2 sites in China.
Trial summary
After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades. We have already finished a prospective trial about apatinib for advanced osteosarcoma(NCT02711007) and find it has a objective response rate of aproximately 45% with… Read more about this study
- Who is it for?
- Ages 11 years and older
- Conditions the study is for
- Progression-free Survival, Overall Survival, Clinical Benefit Rate
- What is being tested?
- Apatinib and SHR-1210
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 2 sitesChina
- Study dates
- 1 Jan 2018to 30 Jan 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 11 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- age more than or equal to 11 years;
- diagnosis confirmed histologically and reviewed centrally;
- prior treatment (completed >4 weeks before trial entry) consisted of standard high-grade osteosarcoma chemotherapy agents including doxorubicin, cisplatin, high- dose methotrexate, and ifosfamide; metastatic relapsed and unresectable progressive disease (PD);
- having measurable lesion according to RECIST 1.1;
- Eastern Cooperative Oncology Group performance status 0-1 with a life expectancy >3 months;
- Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment)as determined by: Hemoglobin ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L (for patients with advanced hepatocellular carcinoma), Platelet count ≥ 100×109/L (for patients with advanced gastric cancer); serum albumin ≥2.8 g/dL; serum total bilirubin (TBIL)≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal(ULN), for subjects with liver metastases, ALT and AST≤5×ULN; Calculated creatinine clearance (CrCl) > 50 mL/min (Cockcroft-Gault formula will be used to calculate CrCl).
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- normal or controlled blood pressure;
- Females of childbearing potential (FOCBP), who are not surgically sterile or postmenopausal, must conduct pregnancy test (serum or urine) within 7 days before enrollment, and must not be pregnant or breast-feeding women.
- surgery and/or radiotherapy completion at least 1 month before enrollment.
- Joining the study voluntarily with good compliance.
Who cannot join
- Patients must not have had prior treatment with camrelizumab or any other PD-L1 or PD-1 antagonists.
- Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration. Note: corticosteroids used for the purpose of IV contrast allergy prophylaxis are allowed.
- Known history of hypersensitivity to any components of the camrelizumab formulation, or other antibody formulation.
- Active central nervous system (CNS) metastases with clinical symptoms (including cerebral edema, steroid requirement, or progressive disease). Subjects with brain or meningeal metastases that were previously treated must be clinically stable (magnetic resonance imaging [MRI] at least 4 weeks apart do not show evidence of new or enlarging metastases) and have discontinued immunosuppressive doses of systemic steroids (> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration.
- Patients with other malignant tumor (except cured skin basal cell carcinoma and cervical carcinoma).
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- Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class > 2), ventricular arrhythmia which need medical intervention, left ventricular ejection fraction(LVEF) < 50%.
- Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents(within 3 months): systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg.
- Coagulation abnormalities (PT>16s、APTT>43s、TT>21s、Fbg<2g/L), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
- Active infection or an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumor fever may be enrolled).
- Previous experience abdomen fistula, gastrointestinal perforation, or abdominal abscess within 4weeks.
- Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, pulmonary function damaged seriously etc.
- History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or active hepatitis (transaminase does not meet the inclusion, hepatitis B virus (HBV) DNA ≥10⁴ /ml or hepatitis C virus (HCV) RNA≥103 /ml or higher); Chronic hepatitis B virus carriers who HBV DNA<2000 IU/ml(<104/ml), must receive anti-viral treatment throughout the study.
- Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results.
Trial locations and contacts
2 sites in 1 country.
China2 sites
Musculoskeletal Tumor Center of Peking University People's Hospital
Beijing, 100044
Peking University Shougang Hospital
Beijing, 100144
About this study
Official title: Apatinib Mesylate Plus Anti-PD1 Therapy (SHR-1210) in Locally Advanced, Unresectable or Metastatic Osteosarcoma(APFAO)Refractory to Chemotherapy : a Single Institution, Open-label, Phase 2 Trial
After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades. We have already finished a prospective trial about apatinib for advanced osteosarcoma(NCT02711007) and find it has a objective response rate of aproximately 45% with median progression-free survival around 5 months. Thus, the investigators explored apatinib activity together with anti-PD1 therapy in order to induce durable response in patients with relapsed and unresectable osteosarcoma after the failure of first-line or second-line chemotherapy.
Apatinib is a small-molecule vascular endothelial growth factors receptor (VEGFR) tyrosine kinase inhibitor, similar to pazopanib, but with a binding affinity 10 times to VEGFR-2 comparing with pazopanib or sorafenib.
SHR-1210 is a humanized anti-PD-1 monoclonal antibody.
Read the detailed description
Patients more than 11 years with body surface area more than 1.2m2, progressing after standard treatment, will be eligible to receive 250 or 500 mg of apatinib once daily together with SHR-1210 3mg/kg (no more than 200mg) iv every 2 weeks until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) at 4 months and overall survival(OS). Secondary objectives were clinical benefit rate (CBR), defined as no progression at 6 months and safety.
- Being tested
- Apatinib, SHR-1210
- Keywords
- osteosarcoma, advanced, apatinib, PD-1
- Medical subject headings
- Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApatinibDrug
Every patients will received apatinib 250mg or 500mg orally daily according to their body surface area (BSA) until disease progression or intolerance to side effects.
SHR-1210Drug
Every patients will received SHR-1210 3mg/kg (no more than 200mg) iv every 2 weeks until disease progression or intolerance to side effects.
| Study group | Role | What they receive |
|---|---|---|
| apatinib plus anti-PD1 therapy arm | Experimental | Every patients will received apatinib 250mg or 500mg orally daily and SHR-1210 3mg/kg (no more than 200mg) iv every 2 weeks until disease progression or intolerance to side effects. Receives: Drug: Apatinib; Drug: SHR-1210 |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival
Progression-free survival is defined as time from enrollment to the first occurrence of progression of disease or death from any cause within 63 days of last response assessment.
Measured: up to approximately 24months
clinical benefit rate
clinical benefit rate is defined as the proportion of patients who achieve disease control (objective response and stable disease according to RECIST 1.1).
Measured: up to approximately 24months
Secondary outcomes (1)
overall survival
overall survival is defined as the duration from date of enrollment to the date of death from any cause.
Measured: up to approximately 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2017
- Study start1 Jan 2018
- Primary completion22 Oct 2019
- Study completion30 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Progression-free SurvivalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Every patients will received apatinib 500mg or 250mg orally daily and SHR-1210 3mg/kg (no more than 200mg) iv every 2 weeks until disease progression or intolerance to side effects
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peking University People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Jiangsu HengRui Medicine Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Wei Guo, M.D.and Ph.D., Principal investigator, Musculoskeletal Tumor Center of Peking University People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03359018
- Sponsor's protocol ID
- PKUPH-sarcoma 02
- Acronym
- APFAO
- Status last verified
- May 2020
- First submitted
- 27 Nov 2017
- Last updated
- 19 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: all collected IPD, all IPD that underlie results in a publication
Publications
Xie L, Xu J, Sun X, Tang X, Yan T, Yang R, Guo W. Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial. Oncologist. 2019 Jul;24(7):e542-e550. doi: 10.1634/theoncologist.2018-0542. Epub 2018 Dec 17.
PubMed 30559126Xie L, Xu J, Sun X, Tang X, Yan T, Yang R, Guo W. Anorexia, Hypertension, Pneumothorax, and Hypothyroidism: Potential Signs of Improved Clinical Outcome Following Apatinib in Advanced Osteosarcoma. Cancer Manag Res. 2020 Jan 7;12:91-102. doi: 10.2147/CMAR.S232823. eCollection 2020.
PubMed 32021426Xie L, Xu J, Sun X, Guo W, Gu J, Liu K, Zheng B, Ren T, Huang Y, Tang X, Yan T, Yang R, Sun K, Shen D, Li Y. Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial. J Immunother Cancer. 2020 May;8(1):e000798. doi: 10.1136/jitc-2020-000798.
PubMed 32376724
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Apatinib Mesylate Plus Anti-PD1 Therapy (SHR-1210) in Locally Advanced, Unresectable or Metastatic Osteosarcoma(APFAO)Refractory to Chemotherapy : a Single Institution, Open-label, Phase 2 Trial
- ClinicalTrials.gov ID
- NCT03359018
- Acronym / sponsor ID
- APFAO / PKUPH-sarcoma 02
- Keywords
- osteosarcoma, advanced, apatinib, PD-1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Peking University People's HospitalUniversity, hospital or other
- Collaborators
- Jiangsu HengRui Medicine Co., Ltd.
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 22 Oct 2019 (actual)
- Study completion
- 30 Jan 2020 (actual)
- First posted
- 2 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
After standard multimodal therapy, the prognosis of relapsed and unresectable high-grade osteosarcoma is dismal and unchanged over the last decades. We have already finished a prospective trial about apatinib for advanced osteosarcoma(NCT02711007) and find it has a objective response rate of aproximately 45% with median progression-free survival around 5 months. Thus, the investigators explored apatinib activity together with anti-PD1 therapy in order to induce durable response in patients with relapsed and unresectable osteosarcoma after the failure of first-line or second-line chemotherapy.
Apatinib is a small-molecule vascular endothelial growth factors receptor (VEGFR) tyrosine kinase inhibitor, similar to pazopanib, but with a binding affinity 10 times to VEGFR-2 comparing with pazopanib or sorafenib.
SHR-1210 is a humanized anti-PD-1 monoclonal antibody.
Detailed description
Patients more than 11 years with body surface area more than 1.2m2, progressing after standard treatment, will be eligible to receive 250 or 500 mg of apatinib once daily together with SHR-1210 3mg/kg (no more than 200mg) iv every 2 weeks until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) at 4 months and overall survival(OS). Secondary objectives were clinical benefit rate (CBR), defined as no progression at 6 months and safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Every patients will received apatinib 500mg or 250mg orally daily and SHR-1210 3mg/kg (no more than 200mg) iv every 2 weeks until disease progression or intolerance to side effects
| Arm | Type | Receives |
|---|---|---|
| apatinib plus anti-PD1 therapy arm | Experimental | Drug: Apatinib, Drug: SHR-1210Every patients will received apatinib 250mg or 500mg orally daily and SHR-1210 3mg/kg (no more than 200mg) iv every 2 weeks until disease progression or intolerance to side effects. |
Who may qualify
- Ages
- 11 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- age more than or equal to 11 years;
- diagnosis confirmed histologically and reviewed centrally;
- prior treatment (completed >4 weeks before trial entry) consisted of standard high-grade osteosarcoma chemotherapy agents including doxorubicin, cisplatin, high- dose methotrexate, and ifosfamide; metastatic relapsed and unresectable progressive disease (PD);
- having measurable lesion according to RECIST 1.1;
- Eastern Cooperative Oncology Group performance status 0-1 with a life expectancy >3 months;
Key exclusion criteria (14 listed)
- Patients must not have had prior treatment with camrelizumab or any other PD-L1 or PD-1 antagonists.
- Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration. Note: corticosteroids used for the purpose of IV contrast allergy prophylaxis are allowed.
- Known history of hypersensitivity to any components of the camrelizumab formulation, or other antibody formulation.
- Active central nervous system (CNS) metastases with clinical symptoms (including cerebral edema, steroid requirement, or progressive disease). Subjects with brain or meningeal metastases that were previously treated must be clinically stable (magnetic resonance imaging [MRI] at least 4 weeks apart do not show evidence of new or enlarging metastases) and have discontinued immunosuppressive doses of systemic steroids (> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApatinibEvery patients will received apatinib 250mg or 500mg orally daily according to their body surface area (BSA) until disease progression or intolerance to side effects. | Drug | apatinib plus anti-PD1 therapy arm |
| SHR-1210Every patients will received SHR-1210 3mg/kg (no more than 200mg) iv every 2 weeks until disease progression or intolerance to side effects. | Drug | apatinib plus anti-PD1 therapy arm |
Primary outcome
progression-free survival
Time frame: up to approximately 24months
Progression-free survival is defined as time from enrollment to the first occurrence of progression of disease or death from any cause within 63 days of last response assessment.
clinical benefit rate
Time frame: up to approximately 24months
clinical benefit rate is defined as the proportion of patients who achieve disease control (objective response and stable disease according to RECIST 1.1).
1 secondary outcome
overall survival
Time frame: up to approximately 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2020.
- Background: PubMed 30559126Xie L, Xu J, Sun X, Tang X, Yan T, Yang R, Guo W. Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial. Oncologist. 2019 Jul;24(7):e542-e550. doi: 10.1634/theoncologist.2018-0542. Epub 2018 Dec 17.
- Background: PubMed 32021426Xie L, Xu J, Sun X, Tang X, Yan T, Yang R, Guo W. Anorexia, Hypertension, Pneumothorax, and Hypothyroidism: Potential Signs of Improved Clinical Outcome Following Apatinib in Advanced Osteosarcoma. Cancer Manag Res. 2020 Jan 7;12:91-102. doi: 10.2147/CMAR.S232823. eCollection 2020.
- Results publication: PubMed 32376724Xie L, Xu J, Sun X, Guo W, Gu J, Liu K, Zheng B, Ren T, Huang Y, Tang X, Yan T, Yang R, Sun K, Shen D, Li Y. Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial. J Immunother Cancer. 2020 May;8(1):e000798. doi: 10.1136/jitc-2020-000798.
- Individual participant dataSharing planned: Yes. all collected IPD, all IPD that underlie results in a publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wei Guo, M.D.and Ph.D. principal investigator
Musculoskeletal Tumor Center of Peking University People's Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apatinib and SHR-1210 in people with Progression-free Survival and Overall Survival, run by Peking University People's Hospital at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
progression-free survival (time frame: up to approximately 24months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03359018, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2020.