Comparison of MAPI+Camrelizumab Versus API+Apatinib Versus MAPI in Patients With a Poor Response to Preoperative Chemotherapy for Newly Diagnosed High-grade Osteosarcoma

Osteosarcoma Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04351308
• Other study ID #: PKUPH-sarcoma 09
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2020
• Est. completion date: December 31, 2022

Study information

• Verified date: May 2020
• Source: Peking University People's Hospital
• Contact: Lu Xie, M.D.
• Phone: +8613401044719
• Email: xie.lu[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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 × 10? cells per L (or a white blood cell count of at least 3 × 10? 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.

Related Conditions & MeSH terms

• Chemotherapy Effect
• Drug-Related Side Effects and Adverse Reactions
• Osteosarcoma
• Survival
• Toxicity, Drug

Intervention

Drug:
• MAPI chemotherapy
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)
• Apatinib Mesylate
anti-angiogenesis tyrosine kinase inhibitors 500 mg orally daily
• Camrelizumab
anti-PD-1 antibody 200mg ivgtt. Q2W

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University People's Hospital	Chinese Sarcoma Study Group

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	event-free survival rate	from initial treatment after definitive surgery to progression/death/ last follow up	2 years
Secondary	overall survival rate	from initial treatment after definitive surgery to death/ last follow up	5 years