Trilaciclib Combing Chemotherapy in the Neoadjuvant Treatment of Osteosarcoma

A Prospective Randomized Phase Ⅱ Study of Trilaciclib Combing Chemotherapy in the Neoadjuvant Treatment of Osteosarcoma

To evaluate the clinical application value in bone marrow protection of Trilaciclib in the neoadjuvant treatment of stage II/III classic osteosarcoma in combination with pirarubicin and lobaplatin.

Study Overview

• Status: Recruiting
• Conditions: Osteosarcoma
• Intervention / Treatment: Drug: Trilaciclib; Drug: Pirarubicin; Drug: Lobaplatin

Detailed Description

Classic osteosarcoma is the most common primary bone malignancy. At present, osteosarcoma is usually treated with preoperative chemotherapy, surgical operation and postoperative chemotherapy. Treatment with preoperative chemotherapy is also known as neoadjuvant chemotherapy. Neoadjuvant chemotherapy has brought benefits to patients, but safety concerns are inevitable. Myelosuppression is a major factor affecting the compliance of patients treated by chemotherapy. Patients with chemotherapy-induced myelosuppression(CIM) have higher rates of infection, sepsis, bleeding, and fatigue, resulting in hospitalization, hematopoietic growth factor support, blood transfusions (red blood cells and/or platelets) and even death. In addition, CIM often leads to dose reduction and delayed administration, which limits the therapeutic dose intensity and therefore affects the anti-tumor efficacy of chemotherapy.

Currently, there are no approved treatments in osteosarcoma to prevent chemotherapy-induced cell damage. Although some treatments may help to address CIM when it occurs such as blood transfusions and growth factors, these treatments are pedigree specific, being used after hematopoietic stem progenitor cells damage and could bring additional toxicity.

Trilaciclib is a highly effective, selective and temporarily reversible inhibitor of CDK4/6. The proliferation of bone marrow hematopoietic stem cells depends on CDK4/6 activity. Bone marrow hematopoietic stem cells are blocked in the G1 phase of the cell cycle after exposure to Trilaciclib before chemotherapy is given.

Therefore, this study is conducted to evaluate the clinical application value in bone marrow protection of Trilaciclib in the neoadjuvant treatment of stage II/III classic osteosarcoma in combination with pirarubicin and lobaplatin.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Peking University People's Hospital
      • Contact: Xin Sun; Phone Number: +86 13810548607; Email: margoshelly@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent signed;
2. Classic osteosarcoma confirmed by histopathology (high grade);
3. Newly diagnosed stage Ⅱ-Ⅲ based on Enneking staging criteria;
4. Planned to receive neoadjuvant chemotherapy;
5. Measurable disease on CT by RECIST 1.1.
6. No antitumor system therapy received;
7. ECOG 0-1
8. Adequate organ function.
9. Females of childbearing potential as well as males and their partners must agree to use an effective form of contraception during the study and for 6 months following the last dose of study medication.

Exclusion Criteria:

1. History of malignancies of other type;
2. Allergic to study agent;
3. History of psychotropic substance abuse, alcohol or drug use;
4. The researchers considered inappropriate to join the study of any cause.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trilaciclib Arm; Neoadjuvant therapy of adding Trilaciclib to Pirarubicin and Lobaplatin	Drug: Trilaciclib; Trilaciclib: 240mg/m2, IV, within 4 hours before each chemotherapy agent infused.; Other Names: Cosela; Drug: Pirarubicin; Pirarubicin: 60 mg/m2，IV，d1-2; Drug: Lobaplatin; LobaplLatin: 40 mg/m2,，IV，d1
Sham Comparator: Control Arm; Neoadjuvant therapy of Pirarubicin and Lobaplatin	Drug: Pirarubicin; Pirarubicin: 60 mg/m2，IV，d1-2; Drug: Lobaplatin; LobaplLatin: 40 mg/m2,，IV，d1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of grade 3/4 neutropenia	Incidence of grade 3/4 neutropenia up to 30 days	up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of grade 3/4 neutropenia	Duration of grade 3/4 neutropenia up to 30 days	up to 30 days
Incidence of grade 3/4 thrombocytopenia	Incidence of grade 3/4 thrombocytopenia up to 30 days	up to 30 days
Incidence of grade 3 or 4 anemia	Incidence of grade 3 or 4 anemia up to 30 days	up to 30 days
Incidence of febrile neutropenia	Incidence of febrile neutropenia up to 30 days	up to 30 days
Usage of granulocyte colony-stimulating factor (G-CSF)	Utilization rate of granulocyte colony-stimulating factor (G-CSF) up to 30 days	up to 30 days
Usage of Thrombopoietin (TPO)	Utilization rate of Thrombopoietin (TPO) up to 30 days	up to 30 days
Usage of Erythropoietin (ESA)	Utilization rate of Erythropoietin (ESA) up to 30 days	up to 30 days
Incidence of platelet transfusion	Incidence of platelet transfusion up to 30 days	up to 30 days
Incidence of red blood cell transfusion	Incidence of red blood cell transfusion up to 30 days	up to 30 days
Usage of ferralia	Utilization rate of ferralia up to 30 days	up to 30 days
chemotherapy dose reduction of any cause	chemotherapy dose reduction rate of any cause up to 30 days	up to 30 days
AE adverse event adverse event adverse event	adverse event	up to 30 days
SAE	serious adverse event serious adverse event serious adverse event Serious Adverse Event	up to 30 days
Termination of treatment caused by AE/SAE	Termination of treatment rate caused by AE/SAE	up to 30 days

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: November 23, 2024
• First Submitted That Met QC Criteria: November 28, 2024
• First Posted (Actual): December 3, 2024

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 28, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Osteosarcoma; Antineoplastic Agents; Pirarubicin
• Other Study ID Numbers: SMA-OS-001

Drug and device information, study documents

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