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

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
      • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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;
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)

Drug: Apatinib Mesylate
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;
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)

Drug: Camrelizumab
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);
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Peking University People's Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Chinese Sarcoma Study Group

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2020

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 15, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 15, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 17, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 19, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 15, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PKUPH-sarcoma 09

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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