A Phase II Clinical Study Evaluating the Safety and Efficacy of Camrelizumab Combined With Chemotherapy and Apatinib as First Line Treatment in Advanced or Metastatic Extrapulmonary Neuroendocrine Carcinomas（EP-NEC）
Overview
- Phase
- Phase 2
- Intervention
- Camrelizumab
- Conditions
- Advanced or Metastatic EP-NEC
- Sponsor
- Huazhong University of Science and Technology
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Overall response rate （ORR）
- Status
- Not yet recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
This is an open-label，single-arm, phase II exploratory study that evaluates the efficacy and safety of Camrelizumab combined with Chemotherapy （carboplatin or cisplatin + etoposide）and Apatinib as First Line treatment in Advanced or Metastatic Extrapulmonary Neuroendocrine Carcinomas（EP-NEC）
Investigators
Xianglin Yuan
Professor
Huazhong University of Science and Technology
Eligibility Criteria
Inclusion Criteria
- •Eligible patients for this study must meet all of the following criteria:
- •Pathologically or cytologically diagnosed as locally advanced or metastases extrapulmonary neuroendocrine carcinoma that cannot be surgically removed.
- •Aged 18-75，male and female
- •Patients who have not received systemic treatment for advanced or metastatic EP-NEC . Subjects who have previously received adjuvant or neoadjuvant therapy (including chemotherapy, radiotherapy or radiochemotherapy) for EP-NEC must have completed the last dose at least 6 months before enrollment . Palliative radiotherapy is permitted, but it must be completed at least 2 weeks prior to the study treatment. The lesions in the irradiation field cannot be used as target lesions for efficacy evaluation, and radiotherapy-related adverse reactions must be restored to at least Grade 0-
- •At least 1 measurable lesion according to RECIST criteria.
- •Adequate organ and bone marrow function, defined as follows:
- •White blood cell count (WBC) ≥ 3,000/mm3 (3.0 × 109/L);
- •Absolute neutrophil count (ANC) ≥ 1,500/mm3 (1.5 × 109/L);
- •Platelet count (PLT) ≥ 100,000/mm3 (100 × 109/L);
- •Hemoglobin (Hb) ≥ 9 g/dL (90 g/L);
Exclusion Criteria
- •Presence of known uncontrolled or symptomatic active central nervous system (CNS) metastasis, manifested as clinical symptoms, cerebral edema, spinal cord compression, cancerous meningitis, leptomeningeal disease, and/or progressive growth. For CNS metastases that have been adequately treated, and neurological symptoms can return to baseline levels at least 2 weeks before enrollment (except for residual signs or symptoms related to CNS treatment), they can be included . In addition, subjects must stop corticosteroids or receive a stable dose of ≤ 10 mg/d or a gradually decreasing dose of prednisone (or an equivalent dose of other corticosteroids) at least 2 weeks before enrollment.
- •Have received the following treatments or drugs before enrollment:
- •① A major operation was performed within 28 days before enrollment (tissue biopsy and peripheral venipuncture for central venous catheterization \[PICC\]/infusion port implantation are allowed).
- •② Using immunosuppressive drugs within 7 days before enrollment, excluding nasal spray and inhaled corticosteroids or physiological doses of systemic steroid hormones (no more than 10 mg/d prednisone or other corticosteroids with equivalent physiological doses)
- •③ within 28 days before enrollment or planned to receive live attenuated vaccine during the study period and 60 days after the end of study drug treatment.
- •④ Receive chemotherapy within 28 days before enrollment;
- •Prior malignancy within 3 years, except adequately treated basal cell carcinoma or squamous cell skin cancer ,superficial bladder cancer, cervical carcinoma in situ, breast ductal carcinoma in situ and papillary thyroid cancer.
- •Prescence of any active, known or suspected autoimmune diseases. Subjects who are in a stable state and do not require systemic immunosuppressive therapy are allowed, such as type I diabetes, hypothyroidism that only requires hormone replacement therapy, and skin diseases that do not require systemic therapy (eg, vitiligo, psoriasis disease and hair loss).
- •Prior treatment with anti-PD-1/PD-L1 antibodies, anti-PD-L2 antibodies, anti-CD137 antibodies, CTLA-4 antibodies, or other drugs/antibodies that act on T cell costimulation or checkpoint pathways.
- •Prescence of clinically significant bleeding symptoms or a clear bleeding tendency within 3 months before enrollment; gastrointestinal perforation and/or gastrointestinal fistula occurred within 6 months before enrollment; 6 before enrollment Arterial/venous thrombosis events that occurred within a month, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism.
Arms & Interventions
Camrelizumab+ Chemotherapy+Apatinib
Induction stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 +Etoposide (100mg/m2 IV continuously on Day 1, 2 and 3）+Carboplatin（AUC 5 mg/mL/min IV on Day 1) or Cisplatin(25mg/m2，continuously on Day 1, 2 and 3) Q3W for 4-6 cycles; Maintenance stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Apatinib capsules 250 mg given orally, once daily in 21-day cycle .
Intervention: Camrelizumab
Camrelizumab+ Chemotherapy+Apatinib
Induction stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 +Etoposide (100mg/m2 IV continuously on Day 1, 2 and 3）+Carboplatin（AUC 5 mg/mL/min IV on Day 1) or Cisplatin(25mg/m2，continuously on Day 1, 2 and 3) Q3W for 4-6 cycles; Maintenance stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Apatinib capsules 250 mg given orally, once daily in 21-day cycle .
Intervention: Etoposide
Camrelizumab+ Chemotherapy+Apatinib
Induction stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 +Etoposide (100mg/m2 IV continuously on Day 1, 2 and 3）+Carboplatin（AUC 5 mg/mL/min IV on Day 1) or Cisplatin(25mg/m2，continuously on Day 1, 2 and 3) Q3W for 4-6 cycles; Maintenance stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Apatinib capsules 250 mg given orally, once daily in 21-day cycle .
Intervention: Carboplatin
Camrelizumab+ Chemotherapy+Apatinib
Induction stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 +Etoposide (100mg/m2 IV continuously on Day 1, 2 and 3）+Carboplatin（AUC 5 mg/mL/min IV on Day 1) or Cisplatin(25mg/m2，continuously on Day 1, 2 and 3) Q3W for 4-6 cycles; Maintenance stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Apatinib capsules 250 mg given orally, once daily in 21-day cycle .
Intervention: Cisplatin
Camrelizumab+ Chemotherapy+Apatinib
Induction stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 +Etoposide (100mg/m2 IV continuously on Day 1, 2 and 3）+Carboplatin（AUC 5 mg/mL/min IV on Day 1) or Cisplatin(25mg/m2，continuously on Day 1, 2 and 3) Q3W for 4-6 cycles; Maintenance stage：Camrelizumab 200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Apatinib capsules 250 mg given orally, once daily in 21-day cycle .
Intervention: Apatinib
Outcomes
Primary Outcomes
Overall response rate （ORR）
Time Frame: 2 years
Defined as percentage of participants achieving complete response (CR) and partial response (PR) assessed by the investigator according to the RECIST 1.1
Secondary Outcomes
- Overall survival (OS)(3 years)
- Progression-Free Survival (PFS)(3 years)
- Duration of Response (DOR)(3 years)
- Disease Control Rate (DCR)(2 years)
- Adverse event (AE)(2 years)