OsteosarcomaPhase 2PROACHNCT03742193
Pulmonary Resectable Metastases of Osteosarcoma With Anti-angiogenics and CHemotherapy
A Phase 2 study testing Apatinib and GD regimen in people with Osteosarcoma and Pulmonary Metastases, run by Ruijin Hospital at 1 site in China.
Trial summary
The aim of this study is to evaluate the efficacy and safety of Second-line chemotherapy combined with Apatinib for the patients with resectable pulmonary metastasis of osteosarcoma. Read more about this study
- Who is it for?
- Ages 10 to 50 years
- Conditions the study is for
- Osteosarcoma, Pulmonary Metastases, Apatinib
- What is being tested?
- Apatinib and GD regimen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteChina
- Study dates
- 11 Aug 2019to 30 Dec 2023
- 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 10 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- age between 10 and 50 years;
- diagnosis of histologically confirmed high grade osteosarcoma;
- identification of pulmonary metastases without the existence of local recurrence(previous re-resection of local recurrence with wide margin is allowed).
- resectable pulmonary nodule(s), defined as nodule(s) that are removable by wedge resection/ segmentectomy/lobectomy without necessitating a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels)
- prior treatment consisted of standard National Comprehensive Cancer Network (NCCN) guideline recommended first-line chemotherapy
- wide/radical-margin surgical resection of the primary tumor completed at least 4 weeks before enrollment.
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- 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;
- no thoracic comorbidities with adequate pulmonary function eligible for thoracic surgery
Who cannot join
- previously exposed to GD chemotherapy or VEGFR2 Tyrosine-kinase inhibitors (TKIs);
- existence of local recurrence;
- 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 ;
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- metastases considered unresectable or borderline resectable at baseline
- intolerable of thoracis surgery
- pleural or peritoneal effusion that needs to be handled by surgical treatment;
- combined with other infections or wounds
- wound dystrophy, poor soft-tissue around implantation or other wound complications risky of non-healing given angiogenesis inhibitor assessed by the investigators
Trial locations and contacts
1 site in 1 country.
China1 site
Ruijin Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200025
About this study
Official title: A Phase II Study of Gemcitabine-docetaxel Chemotherapy With Anti-angiogenic Therapy for Pulmonary Resectable Metastases of Osteosarcoma
The aim of this study is to evaluate the efficacy and safety of Second-line chemotherapy combined with Apatinib for the patients with resectable pulmonary metastasis of osteosarcoma.
Read the detailed description
After standard chemotherapy and surgery for the localized disease, pulmonary metastases of osteosarcoma occurs in up to 40% of cases and still remain challenging without satisfactory regimen. Apatinib is a oral kinase inhibitor of receptor tyrosine targeting VEGFR2. A pilot study indicated that Apatinib improved the PFS after multi-line chemotherapy failure, and might partly reversed chemo-refractory status for advanced osteosarcoma. Thus, the investigators explored the efficacy of combining Apatinib with current available second-line chemotherapy compared to chemotherapy alone for treating first resectable pulmonary metastases of osteosarcoma following the failure of first-line chemotherapy and wide/radical-margin surgery. Participants will receive 250 mg of apatinib twice daily combined with gemcitabine-docetaxel (GD) regimen before and after the surgical resection of the pulmonary metastases. Osteosarcoma patients with pulmonary recurrence only at baseline will be recruited in the study. The primary end point is progression-free survival rate (PFR) compared with historical control. A12 month PFR of 30% or less is considered inactive, while a 12 month PFR of 50% or greater is regarded as of interest for additional development. With a type I error rate of 5% and a power of 83%, the number of patients needed for this design is 43.
- Conditions
- Osteosarcoma, Pulmonary Metastases, Apatinib
- Being tested
- Apatinib, GD regimen
- Medical subject headings
- Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApatinibDrug
Also called VEGFR Inhibitor
Apatinib 250mg tablet by mouth, bid. 48 hrs break before and 96 hrs after the surgical resection of the pulmonary metastases.
GD regimenDrug
Also called Chemotherapy
One cycle: gemcitabine 900 mg/m^2 over 90 min on Day 1, and gemcitabine 900 mg/m^2 and docetaxel 75 mg/m^2 on Day 8. Every 21 days were eligible.
1~2 -week break before and 2-week break after the surgical resection of the pulmonary metastases is taken.
| Study group | Role | What they receive |
|---|---|---|
| Apatinib + GD group | Experimental | Apatinib + GD regimen. For unilateral metastases,3 cycles before metastasectomy, and 4 cycles after. For bilateral metastases, 3 cycles before first metastasectomy, 1 cycle inbetween, and then second metastasectomy followed by 4 cycles. Apatinib monotherapy is then maintained until 1 year following complete resection. Receives: Drug: Apatinib; Drug: GD regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
12 months Progression-free survival rate(12mPFR)
The proportion of patients with progression-free survival at 12 months according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). A 12mPFR of 30% or less is considered inactive, while a 12mPFR of 50% or greater is regarded as of interest for additional development
Measured: 12 months from the recruitment of the study
Secondary outcomes (7)
Overall survival (OS)
calculated from the date of treatment start until last follow-up or death, whichever comes first.
Measured: Baseline until death, followed through study completion, an average of 2 years
Total resectability
The number of patients undergoing pre-planned metastasectomy divided by the number of patients considered resectable at baseline
Measured: after neoadjuvant systemic therapy, an average of 8~9 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The occurrence of each adverse events(AEs), severe AEs(SAEs) and death according the CTCAE_5.0
Measured: through study completion, an average of 1 years
Objective response rate (ORR)
Complete Response(CR)+Partial Response(PR) after neoadjuvant systemic therapy
Measured: after neoadjuvant systemic therapy, an average of 8~9 weeks
Clinical benefit rate (CBR)
CR+PR+stable disease (SD) after neoadjuvant systemic therapy
Measured: after neoadjuvant systemic therapy, an average of 8~9 weeks
Progression free survival (PFS)
Progression free survival according to RECIST 1.1
Measured: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
OS rate
the proportion of OS at 12, 24 months
Measured: 12 and 24 months from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2018
- Study start11 Aug 2019
- Primary completion15 Nov 2023 (estimated)
- Study completion30 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- More trials run by Ruijin HospitalThe sponsor's other registered studies.
- 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
- Masking
- None (open label)
- Enrolment
- 43 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Weibin Zhang, MD, PhD., Ruijin Hospital
- Investigators
- Weibin Zhang, PhD, MD, Principal investigator, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03742193
- Sponsor's protocol ID
- 2018LLS-NO.84-3
- Acronym
- PROACH
- Status last verified
- Oct 2023
- First submitted
- 25 Sep 2018
- Last updated
- 1 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The data of IPD is available to researcher's upon reasonable request, in accordance to the local legislator's policy ( such as genetic sequencing data)
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Gemcitabine-docetaxel Chemotherapy With Anti-angiogenic Therapy for Pulmonary Resectable Metastases of Osteosarcoma
- ClinicalTrials.gov ID
- NCT03742193
- Acronym / sponsor ID
- PROACH / 2018LLS-NO.84-3
- Conditions
- Osteosarcoma, Pulmonary Metastases, Apatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 43 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- 11 Aug 2019 (actual)
- Primary completion
- 15 Nov 2023 (estimated)
- Study completion
- 30 Dec 2023 (estimated)
- First posted
- 15 Nov 2018 (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.
The aim of this study is to evaluate the efficacy and safety of Second-line chemotherapy combined with Apatinib for the patients with resectable pulmonary metastasis of osteosarcoma.
Detailed description
After standard chemotherapy and surgery for the localized disease, pulmonary metastases of osteosarcoma occurs in up to 40% of cases and still remain challenging without satisfactory regimen. Apatinib is a oral kinase inhibitor of receptor tyrosine targeting VEGFR2. A pilot study indicated that Apatinib improved the PFS after multi-line chemotherapy failure, and might partly reversed chemo-refractory status for advanced osteosarcoma. Thus, the investigators explored the efficacy of combining Apatinib with current available second-line chemotherapy compared to chemotherapy alone for treating first resectable pulmonary metastases of osteosarcoma following the failure of first-line chemotherapy and wide/radical-margin surgery. Participants will receive 250 mg of apatinib twice daily combined with gemcitabine-docetaxel (GD) regimen before and after the surgical resection of the pulmonary metastases. Osteosarcoma patients with pulmonary recurrence only at baseline will be recruited in the study. The primary end point is progression-free survival rate (PFR) compared with historical control. A12 month PFR of 30% or less is considered inactive, while a 12 month PFR of 50% or greater is regarded as of interest for additional development. With a type I error rate of 5% and a power of 83%, the number of patients needed for this design is 43.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Apatinib + GD group | Experimental | Drug: Apatinib, Drug: GD regimenApatinib + GD regimen. For unilateral metastases,3 cycles before metastasectomy, and 4 cycles after. For bilateral metastases, 3 cycles before first metastasectomy, 1 cycle inbetween, and then second metastasectomy followed by 4 cycles. Apatinib monotherapy is then maintained until 1 year following complete resection. |
Who may qualify
- Ages
- 10 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- age between 10 and 50 years;
- diagnosis of histologically confirmed high grade osteosarcoma;
- identification of pulmonary metastases without the existence of local recurrence(previous re-resection of local recurrence with wide margin is allowed).
- resectable pulmonary nodule(s), defined as nodule(s) that are removable by wedge resection/ segmentectomy/lobectomy without necessitating a pneumonectomy (e.g., nodules immediately adjacent to the main stem bronchus or main pulmonary vessels)
- prior treatment consisted of standard National Comprehensive Cancer Network (NCCN) guideline recommended first-line chemotherapy
Key exclusion criteria (11 listed)
- previously exposed to GD chemotherapy or VEGFR2 Tyrosine-kinase inhibitors (TKIs);
- existence of local recurrence;
- have had other kinds of malignant tumors at the same time;
- cardiac insufficiency or arrhythmia;
- uncontrolled complications, such as diabetes mellitus and so on;
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 |
|---|---|---|
| ApatinibAlso: VEGFR InhibitorApatinib 250mg tablet by mouth, bid. 48 hrs break before and 96 hrs after the surgical resection of the pulmonary metastases. | Drug | Apatinib + GD group |
| GD regimenAlso: ChemotherapyOne cycle: gemcitabine 900 mg/m^2 over 90 min on Day 1, and gemcitabine 900 mg/m^2 and docetaxel 75 mg/m^2 on Day 8. Every 21 days were eligible. 1~2 -week break before and 2-week break after the surgical resection of the pulmonary metastases is taken. | Drug | Apatinib + GD group |
Primary outcome
12 months Progression-free survival rate(12mPFR)
Time frame: 12 months from the recruitment of the study
The proportion of patients with progression-free survival at 12 months according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). A 12mPFR of 30% or less is considered inactive, while a 12mPFR of 50% or greater is regarded as of interest for additional development
7 secondary outcomes
Overall survival (OS)
Time frame: Baseline until death, followed through study completion, an average of 2 years
Total resectability
Time frame: after neoadjuvant systemic therapy, an average of 8~9 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: through study completion, an average of 1 years
Objective response rate (ORR)
Time frame: after neoadjuvant systemic therapy, an average of 8~9 weeks
Clinical benefit rate (CBR)
Time frame: after neoadjuvant systemic therapy, an average of 8~9 weeks
Progression free survival (PFS)
Time frame: Baseline until disease progression or death, whichever occurs first (followed through study completion, an average of 1.5 years)
OS rate
Time frame: 12 and 24 months from baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2023.
- Individual participant dataSharing planned: No. The data of IPD is available to researcher's upon reasonable request, in accordance to the local legislator's policy ( such as genetic sequencing data)
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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.
Weibin Zhang, PhD, MD principal investigator
Ruijin Hospital
1 site 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 GD regimen in people with Osteosarcoma and Pulmonary Metastases, run by Ruijin Hospital at 1 site 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 11 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: status not confirmed, as of the sponsor's last update on 1 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Results are not available in the source record.
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?
12 months Progression-free survival rate(12mPFR) (time frame: 12 months from the recruitment of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Nov 2023.