Back to resultsComparison of MAPI+Camrelizumab Versus API+Apatinib Versus MAPI in Patients With a Poor Response to Preoperative Chemotherapy for Newly Diagnosed High-grade Osteosarcoma (MAPAC)
Primary Purpose
Osteosarcoma, Survival, Chemotherapy Effect
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
MAPI chemotherapy
Apatinib Mesylate
Camrelizumab
Sponsored by
About this trial
This is an interventional treatment trial for Osteosarcoma focused on measuring osteosarcoma, doxirubicin, cisplatin, methotrexate, ifosfamide, apatinib, camrelizumab
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed high-grade osteosarcoma, including second malignancies
- Tumor (primary, metastatic, or both) resectable OR is expected to become resectable after neoadjuvant induction chemotherapy
- Suitable for neoadjuvant chemotherapy and adjuvant chemotherapy
- Performance status - Lansky 50-100% (for patients under 16 years of age); Performance status - WHO or ECOG 0-2 with a life expectancy >3 months
- normal cardiac function (shortening fraction >28%), normal hearing, normal bone marrow as shown by an absolute neutrophil count of at least 1·5 × 10⁹ cells per L (or a white blood cell count of at least 3 × 10⁹ cells per L if neutrophil count is not available), and a platelet count of at least 100 000 platelets per μL
- Patients were also required to have a serum bilirubin concentration of at most less than 1·5 times the upper limit of normal and a normal creatinine concentration for their age as per protocol
- Women of child-bearing potential had to take adequate contraceptive measures and have a negative pregnancy test within 7 days of study entry.
Exclusion Criteria:
- patients who have recieved anti-angiogenic TKIs or anti-PD-1/PD-L1 antibodies
- allergy to chemotherapy or apatinib or camrelizumab
- other severe illness (eg, psychosis or previous history of cardiovascular disease)
- symptomatic or known CNS metastases
- previous or concurrent second primary malignant tumours
- had uncontrolled complications such as diabetes mellitus, coagulation disorders, urine protein ≥ ++, and so on
- had other infections or wounds
- pregnant or breastfeeding.
Sites / Locations
- Peking University People's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
API+apatinib
MAPI+camrelizumab
MAPI
Arm Description
AP = Doxorubicin (Adriamycin) 20 mg/m2/day * 2 day (total/cycle 40 mg/m²) + Cisplatin 100 mg/m2/course (total/cycle 120 mg/m²); I = Ifosfamide 2000 mg/m2/day *5 day (total/cycle 10000 mg/m²); apatinib = 500 mg QD;
AP = Doxorubicin (Adriamycin) 37.5 mg/m2/day * 2day (total/cycle 75 mg/m²) + Cisplatin 120 mg/m2/course (total/cycle 120 mg/m²); M = Methotrexate 12000 mg/m2 (total/cycle 12000 mg/m²) with leucovorin rescue; I = Ifosfamide 2400 mg/m2/day *5day (total/cycle 12000 mg/m²); camralizumab = 200mg ivgtt. Q2W;
AP = Doxorubicin (Adriamycin) 37.5 mg/m2/day * 2day (total/cycle 75 mg/m²) + Cisplatin 120 mg/m2/course (total/cycle 120 mg/m²); M = Methotrexate 12000 mg/m2 (total/cycle 12000 mg/m²) with leucovorin rescue; I = Ifosfamide 2400 mg/m2/day *5day (total/cycle 12000 mg/m²);
Outcomes
Primary Outcome Measures
event-free survival rate
from initial treatment after definitive surgery to progression/death/ last follow up
Secondary Outcome Measures
overall survival rate
from initial treatment after definitive surgery to death/ last follow up
Full Information
NCT ID
NCT04351308
First Posted
April 15, 2020
Last Updated
May 15, 2020
Sponsor
Peking University People's Hospital
Collaborators
Chinese Sarcoma Study Group
1. Study Identification
Unique Protocol Identification Number
NCT04351308
Brief Title
Comparison of MAPI+Camrelizumab Versus API+Apatinib Versus MAPI in Patients With a Poor Response to Preoperative Chemotherapy for Newly Diagnosed High-grade Osteosarcoma
Acronym
MAPAC
Official Title
A Randomized Trial of Comparison of MAPI+Camrelizumbab Verus API+Apatinib Versus MAPI in Patients With a Poor Response to Preoperative Chemotherapy for Newly Diagnosed High-grade Osteosarcomaies : an Open-label, Exploratory Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Unknown status
Study Start Date
May 1, 2020 (Actual)
Primary Completion Date
September 1, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking University People's Hospital
Collaborators
Chinese Sarcoma Study Group
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Treatment strategies for high-grade osteosarcoma with multidrug chemotherapy and resection result in 3-year event-free survival of 60-70%. The most common factors predicting survival are presence of metastases, histological response to preoperative chemotherapy and complete surgical resection. Four of the active drugs in osteosarcoma include cisplatin, doxorubicin, high-dose methotrexate and ifosfamide and this combination (MAPI), given preoperatively and postoperatively, is widely used for the treatment of osteosarcoma in China. Apatinib also has activity in advanced setting and when incorporated into the treatment of patients with metastatic disease seemed to improve progression-free survival. Combination of apatinib and camrelizumab resulted in durable therapuetic effect in selected cases. Though EURAMOUS-1 suggested that changing chemotherapy postoperatively on the basis of histological response did not improve outcomes. The exploratory study with radomised design to compare combination of chemotherapy with target drug or combination of chemotherapy with anti-PD-1 antibody versus standard chemotherapy has not been tried yet. Thus we aim to investigate the efficacy and toxicity of these combiantions versus standard chemotherapy in this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteosarcoma, Survival, Chemotherapy Effect, Toxicity, Drug
Keywords
osteosarcoma, doxirubicin, cisplatin, methotrexate, ifosfamide, apatinib, camrelizumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
API+apatinib
Arm Type
Experimental
Arm Description
AP = Doxorubicin (Adriamycin) 20 mg/m2/day * 2 day (total/cycle 40 mg/m²)
+ Cisplatin 100 mg/m2/course (total/cycle 120 mg/m²);
I = Ifosfamide 2000 mg/m2/day *5 day (total/cycle 10000 mg/m²);
apatinib = 500 mg QD;
Arm Title
MAPI+camrelizumab
Arm Type
Experimental
Arm Description
AP = Doxorubicin (Adriamycin) 37.5 mg/m2/day * 2day (total/cycle 75 mg/m²)
+ Cisplatin 120 mg/m2/course (total/cycle 120 mg/m²);
M = Methotrexate 12000 mg/m2 (total/cycle 12000 mg/m²) with leucovorin rescue;
I = Ifosfamide 2400 mg/m2/day *5day (total/cycle 12000 mg/m²);
camralizumab = 200mg ivgtt. Q2W;
Arm Title
MAPI
Arm Type
Active Comparator
Arm Description
AP = Doxorubicin (Adriamycin) 37.5 mg/m2/day * 2day (total/cycle 75 mg/m²)
+ Cisplatin 120 mg/m2/course (total/cycle 120 mg/m²);
M = Methotrexate 12000 mg/m2 (total/cycle 12000 mg/m²) with leucovorin rescue;
I = Ifosfamide 2400 mg/m2/day *5day (total/cycle 12000 mg/m²);
Intervention Type
Drug
Intervention Name(s)
MAPI chemotherapy
Intervention Description
AP = Doxorubicin (Adriamycin) 37.5 mg/m2/day * 2day (total/cycle 75 mg/m²)
+ Cisplatin 120 mg/m2/course (total/cycle 120 mg/m²) ; M = Methotrexate 12000 mg/m2 (total/cycle 12000 mg/m²) with leucovorin rescue; I = Ifosfamide 2400 mg/m2/day *5day (total/cycle 12000 mg/m²)
Intervention Type
Drug
Intervention Name(s)
Apatinib Mesylate
Intervention Description
anti-angiogenesis tyrosine kinase inhibitors 500 mg orally daily
Intervention Type
Drug
Intervention Name(s)
Camrelizumab
Intervention Description
anti-PD-1 antibody 200mg ivgtt. Q2W
Primary Outcome Measure Information:
Title
event-free survival rate
Description
from initial treatment after definitive surgery to progression/death/ last follow up
Time Frame
2 years
Secondary Outcome Measure Information:
Title
overall survival rate
Description
from initial treatment after definitive surgery to death/ last follow up
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed high-grade osteosarcoma, including second malignancies
Tumor (primary, metastatic, or both) resectable OR is expected to become resectable after neoadjuvant induction chemotherapy
Suitable for neoadjuvant chemotherapy and adjuvant chemotherapy
Performance status - Lansky 50-100% (for patients under 16 years of age); Performance status - WHO or ECOG 0-2 with a life expectancy >3 months
normal cardiac function (shortening fraction >28%), normal hearing, normal bone marrow as shown by an absolute neutrophil count of at least 1·5 × 10⁹ cells per L (or a white blood cell count of at least 3 × 10⁹ cells per L if neutrophil count is not available), and a platelet count of at least 100 000 platelets per μL
Patients were also required to have a serum bilirubin concentration of at most less than 1·5 times the upper limit of normal and a normal creatinine concentration for their age as per protocol
Women of child-bearing potential had to take adequate contraceptive measures and have a negative pregnancy test within 7 days of study entry.
Exclusion Criteria:
patients who have recieved anti-angiogenic TKIs or anti-PD-1/PD-L1 antibodies
allergy to chemotherapy or apatinib or camrelizumab
other severe illness (eg, psychosis or previous history of cardiovascular disease)
symptomatic or known CNS metastases
previous or concurrent second primary malignant tumours
had uncontrolled complications such as diabetes mellitus, coagulation disorders, urine protein ≥ ++, and so on
had other infections or wounds
pregnant or breastfeeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lu Xie, M.D.
Phone
+8613401044719
Email
xie.lu@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xin Sun, M.D.
Phone
+8613810548607
Email
xinsun1981@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei Guo, M.D.
Organizational Affiliation
Musculoskeletal Tumor Center of Peking University People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University People's Hospital
City
Beijing
ZIP/Postal Code
100044
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lu Xie, M.D.
Phone
+8613401044719
Email
xie.lu@hotmail.com
First Name & Middle Initial & Last Name & Degree
Xin Sun, M.D.
Phone
+8613810548607
Email
xinsun1981@hotmail.com
First Name & Middle Initial & Last Name & Degree
Wei Guo, M.D. and Ph.D.
12. IPD Sharing Statement
Learn more about this trial
Comparison of MAPI+Camrelizumab Versus API+Apatinib Versus MAPI in Patients With a Poor Response to Preoperative Chemotherapy for Newly Diagnosed High-grade Osteosarcoma
We'll reach out to this number within 24 hrs