Study of Camrelizumab in Combination With Neoadjuvant Chemotherapy in the Treatment of Osteosarcoma

A Phase Ⅱ ,Open-label ,Single Institution Study to Investigate the Efficacy and Safety of Camrelizumab in Combination With Neoadjuvant Chemotherapy in the Treatment of Locally , Resectable Osteosarcoma

This study is a open-lable, , single center, phase II clinical study. Target population is patients with locally resectable osteosarcoma. Study objective is to compare the efficacy and safety of camrelizumab in combination with adriamycin, cisplatin, ifosfamide and methotrexate in study population in China. Camrelizumab is a humanized anti-PD1 IgG4 monoclonal antibody.

Study Overview

• Status: Recruiting
• Conditions: Osteosarcoma
• Intervention / Treatment: Drug: Camrelizumab in Combination With Neoadjuvant Chemotherapy

Detailed Description

In this study, eligible subject will be enrolled into study arm to accept study treatment. Treatment cycles of chemotherapy will be at most 9 cycles which will be decided by investigators. The percentage of the patient with tumor cell necrosis rate >90% determined by the Independent Review Committee (IRC) will be the primary outcome measures.

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jin Wang, MD; Phone Number: 020-87343910; Email: wangjinr@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer Center of Sun-Yat Sen University (CCSYSU)
      • Contact: Jin Wang, MD; Phone Number: 020-87343910; Email: wangjinr@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 14 to 65 year old
2. Eastern Cooperative Oncology Group performance status 0-1
3. Histopathologically diagnosed osteosarcomas (except for paraspesarcomas ), have been evaluated in patients have achieved normative resection with neoadjuvant chemotherapy
4. Having measurable lesion according to RECIST 1.1
5. Life expectancy >3 months
6. Patients must have adequate organ function
7. Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 120 days after last study drug administration. Women of childbearing potential must have a negative pregnancy test ≤ 72 hours prior to Day 1 of study
8. Voluntary informed consent , joining the study with good compliance

Exclusion Criteria:

1. pregnant or lactating women
2. Known history of hypersensitivity to any components of the camrelizumab formulation, or other antibody formulation.
3. Active central nervous system (CNS) metastases with clinical symptoms , including cerebral edema, steroid requirement, or progressive disease.
4. Patients with other malignant tumor within 5 years , except cured skin basal cell carcinoma, cervical carcinoma and Papillary carcinoma of thyroid.
5. Clinically significant cardiovascular diseases
6. Patients have had prior treatment with PD-1/PD-L1 or CTLA-4 antagonists.Received any study drug within 4 weeks prior to the first study drug administration. Enroll in another clinical study, unless it is an observational (non-interventional) clinical study or an intervention follow-up study. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration. Note: corticosteroids used for the allergy and nausea, vomiting are allowed. Inhaled or topical use of steroids and adrenocorticosteroid replacement in doses greater than 10mg/ day is permitted in the absence of active autoimmune disease.Patients who have received a live vaccine within 30 days prior to the first study drug administration.Major surgery or major trauma within 4 weeks of first study drug administration. Left ventricular ejection fraction (LVEF) is more than 60% .

(7)Severe infection occurred within 4 weeks before the first first study drug administration (CTC AE > grade 2) (8)Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded. Stable dose of insulin for type 1 diabetes.

(9)History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or organ transplantation and bone marrow transplantation.

(10)Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, pulmonary function damaged seriously etc.

(11)History of active pulmonary tuberculosis infection, or with a history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or with a history of active pulmonary tuberculosis infection prior to 1 year but without formal treatment.

(12)Active hepatitis (transaminase does not meet the inclusion, hepatitis B virus (HBV) DNA ≥10⁴ /ml or hepatitis C virus (HCV) RNA≥103 /ml or higher); Chronic hepatitis B virus carriers who HBV DNA<2000 IU/ml(<104/ml), must receive anti-viral treatment throughout the study.

(13)Known history of psychotropic substance abuse, alcohol abuse and drug abuse.

(14)The investigators did not think the participants were suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; camrelizumab in combination with adriamycin, cisplatin, ifosfamide and methotrexate	Drug: Camrelizumab in Combination With Neoadjuvant Chemotherapy; camrelizumab in combination with adriamycin, cisplatin, ifosfamide and methotrexate; Other Names: PD-1 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
tumor cell necrosis rate (TCNR)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 years Overall Survival (OS) rate	The percentage of patients overall survival in 2 years	24 months
2 years Progression-free survival (PFS) rate	The percentage of patients Progression-free survival in 2 years	24 months
Adverse Events (AEs)	All adverse event/Serious adverse event that occurred during the study period according to CTCAE	24 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2019
• Primary Completion (Anticipated): March 16, 2021
• Study Completion (Anticipated): September 16, 2023

Study Registration Dates

• First Submitted: February 26, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 4, 2020

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Osteosarcoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors
• Other Study ID Numbers: OBU-STS-II-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No