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

May 15, 2020 updated by: Peking University People's Hospital

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

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.

Study Overview

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Beijing, China, 100044
        • Recruiting
        • Peking University People's Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Wei Guo, M.D. and Ph.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: API+apatinib

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)

anti-angiogenesis tyrosine kinase inhibitors 500 mg orally daily
Experimental: MAPI+camrelizumab

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)

anti-PD-1 antibody 200mg ivgtt. Q2W
Active Comparator: MAPI

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);

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
event-free survival rate
Time Frame: 2 years
from initial treatment after definitive surgery to progression/death/ last follow up
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival rate
Time Frame: 5 years
from initial treatment after definitive surgery to death/ last follow up
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2020

Primary Completion (Anticipated)

September 1, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

April 15, 2020

First Submitted That Met QC Criteria

April 15, 2020

First Posted (Actual)

April 17, 2020

Study Record Updates

Last Update Posted (Actual)

May 19, 2020

Last Update Submitted That Met QC Criteria

May 15, 2020

Last Verified

May 1, 2020

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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