Phase I/II Clinical Study on the Safety and Effectiveness of Pucotenlimab Combined With Standard Chemotherapy Regimen as Neoadjuvant Therapy for Children and Adolescents With Intermediate/High-Risk Rhabdomyosarcoma
Overview
- Phase
- Phase 1
- Intervention
- Pucotenlimab
- Conditions
- Rhabdomyosarcoma
- Sponsor
- Sun Yat-sen University
- Enrollment
- 82
- Locations
- 1
- Primary Endpoint
- DLT
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This study comprises both Phase I and Phase II research. This phase focuses on safety, tolerability, and pharmacokinetics using a "3+3" dose escalation design with three dose groups: 1 mg/kg, 3 mg/kg, and 6 mg/kg. The drug will be administered in combination with the standard regimen for intermediate/high-risk rhabdomyosarcoma once every three weeks (Q3W). In phase II study, all subjects will receive Pucotenlimab combined with the standard regimen for intermediate/high-risk rhabdomyosarcoma for 2-4 cycles of neoadjuvant therapy every 3 weeks (Q3W), followed by surgery.
Investigators
Yizhuo Zhang
Chief of Department of pediatric oncology
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •Age: 1-18 years old;
- •ECOG PS score: 0-1 points;
- •Pathologically confirmed newly diagnosed children or adolescents with intermediate to high-risk rhabdomyosarcoma;
- •Patients evaluated by surgery as having a high degree of difficulty;
- •Must have at least one measurable lesion defined by RECIST or WHO criteria;
- •Expected survival time ≥ 6 months;
- •Cardiac function:
- •Echocardiography shows LVEF ≥ 50%;
- •EKG indicates no evidence of myocardial ischemia;
- •No history of arrhythmia requiring pharmacological intervention before enrollment;
Exclusion Criteria
- •Received anti-PD-1 or anti-PD-L1 monoclonal antibodies or targeted drugs related to these pathways;
- •Received chemotherapy, radiotherapy, or other treatments;
- •Previous surgical treatment (excluding biopsy);
- •Known allergy to PD-1 monoclonal antibodies or any of their excipients; known history of allergic diseases or severe allergies;
- •Having other malignant tumor diseases besides the tumor being treated in this study, excluding: malignant tumors that have been cured and have not recurred within 3 years before enrollment, completely resected basal cell and squamous cell skin cancers, completely resected carcinoma in situ of any type;
- •Active central nervous system metastases (whether treated or not), including symptomatic brain metastases, meningeal metastases, or spinal cord compression, etc. Excluding: asymptomatic brain metastases without progression within at least 4 weeks after radiotherapy and/or without neurological symptoms or signs after surgical resection, without the need for dexamethasone or mannitol treatment.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage;
- •Previous treatment toxicity still \> Grade 1 (CTCAE V4.03 criteria), excluding alopecia and neurotoxicity;
- •History of mental disorders;
- •History of drug abuse or substance abuse upon inquiry;
Arms & Interventions
Pucotenlimab Combined with Standard Chemotherapy Regimen
In phase I, it focuses on safety, tolerability, and pharmacokinetics using a "3+3" dose escalation design with three dose groups: 1 mg/kg, 3 mg/kg, and 6 mg/kg. The drug will be administered in combination with the standard regimen for intermediate/high-risk rhabdomyosarcoma once every three weeks (Q3W). In phase II, after establishing the recommended Phase II dose (RP2D), ll subjects will receive Pucotenlimab combined with the standard regimen for intermediate/high-risk rhabdomyosarcoma for 2-4 cycles of neoadjuvant therapy every 3 weeks (Q3W), followed by surgery. The standard regimen for intermidiate/high-risk rhabdomyosarcoma refer to the SYSUCC-RMS-2017 in China.
Intervention: Pucotenlimab
Outcomes
Primary Outcomes
DLT
Time Frame: within 28 days of the dose escalation phase.
dose-limiting toxicity
pCR
Time Frame: from treatment of pucotenlimab to the surgery
pathological complete response rate