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

NCT04351308 | Unknown Phase 2 DMC

• 1 other identifier: PKUPH-sarcoma 09
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteosarcoma; Survival; Chemotherapy Effect; Toxicity, Drug

Keywords

osteosarcoma; doxirubicin; cisplatin; methotrexate; ifosfamide; apatinib; camrelizumab

Outcome Measures

Primary Outcomes (1)

• event-free survival rate

  from initial treatment after definitive surgery to progression/death/ last follow up

  2 years

Secondary Outcomes (1)

• overall survival rate

  5 years

Study Arms (3)

API+apatinib

EXPERIMENTAL

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; Drug: Apatinib Mesylate

MAPI+camrelizumab

EXPERIMENTAL

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; Drug: Camrelizumab

MAPI

ACTIVE COMPARATOR

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

Interventions

MAPI chemotherapy DRUG

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)

API+apatinib; MAPI; MAPI+camrelizumab

Apatinib Mesylate DRUG

anti-angiogenesis tyrosine kinase inhibitors 500 mg orally daily

API+apatinib

Camrelizumab DRUG

anti-PD-1 antibody 200mg ivgtt. Q2W

MAPI+camrelizumab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Chinese Sarcoma Study Group: collaborator

Study Sites (1)

Peking University People's Hospital

Beijing, 100044, China

RECRUITING

MeSH Terms

Conditions

Osteosarcoma; Drug-Related Side Effects and Adverse Reactions

Interventions

apatinib; camrelizumab

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Chemically-Induced Disorders

Study Officials

• Wei Guo, M.D.

  Musculoskeletal Tumor Center of Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lu Xie, M.D.

CONTACT

+8613401044719; xie.lu@hotmail.com

Xin Sun, M.D.

CONTACT

+8613810548607; xinsun1981@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2020
• First Posted: April 17, 2020
• Study Start: May 1, 2020
• Primary Completion: September 1, 2022
• Study Completion: December 31, 2022
• Last Updated: May 19, 2020

Record last verified: 2020-05

Locations

CN (1)