Chemotherapy/Avelumab Plus Radiotherapy to Primary Esophageal Tumor for Newly Diagnosed Metastatic Esophageal Squamous Cell Carcinoma: The Ave-CRT Study
Overview
- Phase
- Phase 2
- Intervention
- Avelumab
- Conditions
- Esophageal Tumor
- Sponsor
- National Taiwan University Hospital
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- overall radiographic response
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a single institutional, single arm, open labeled phase II study to assess the overall radiographic response of adding Avelumab to chemotherapy and palliative radiotherapy in patients with metastatic advanced esophageal squamous cell carcinoma.
Detailed Description
Avelumab belongs to the group of immune checkpoint blockade cancer therapies. Avelumab binds to the programmed death-ligand 1 (PD-L1) and therefore inhibits binding to its receptor programmed cell death 1 (PD-1). In the case of avelumab, the formation of PD-1/PDL1 ligand pairs is blocked and CD8+ T cell immune response should be increased. This study comprises 2 phases, the concurrent immune-chemoradiotherapy (Ave-PF-CRT) phase and the immune-chemotherapy (Ave-PF) phase. In the immune-chemoradiotherapy phase, patients are treated with PF-CRT and concomitant Avelumab. In the immune-chemotherapy phase, patients are treated with PF plus Avelumab. Overall radiological response, time to progression, overall survival and adverse events will be evaluated. Subjects' health-related quality of life will be assessed as well.
Investigators
Eligibility Criteria
Inclusion Criteria
- •To be eligible for inclusion, patients must fulfill the following criteria:
- •Histologically proved squamous cell carcinoma of esophagus
- •Metastatic disease, which are defined by TNM system of American Joint Committee on Cancer (AJCC) Cancer Staging System (8th edition) in 2017, involving distant lymph node (para-aortic or cervical) metastasis and/or visceral metastasis (lung, liver) documented by radiological examinations
- •Age ≥ 20 years
- •ECOG Performance Status 0 or 1
- •Adequate bone marrow reserves within 2 weeks prior to registration, defined as:a. absolute neutrophil count (ANC) ≥ 1.5×109/L (1,500/μl)b. platelets ≥ 100×109/L (100,000/µl)c. hemoglobin ≥ 9.0 g/dl (may have been transfused)
- •Adequate liver function reserves within 2 weeks prior to registration, defined as:
- •hepatic transaminases (AST and ALT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 × ULN for subjects with documented metastatic disease to liver
- •serum total bilirubin ≤ 2.5 × upper limit of normal (ULN)
- •Adequate renal function within 2 weeks prior to registration: Creatinine ≤1.5 mg/dL
Exclusion Criteria
- •Patients fulfill any of the following criteria will be excluded from this trial
- •Prior radiotherapy to head and neck, chest, or abdomen
- •Tumor invasion to adjacent structures (T4 lesion)
- •Adenocarcinoma of esophagus or gastroesophageal junction.
- •No measurable metastatic target lesion(s) by RECIST criteria
- •Synchronously or metachronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer
- •Prior invasive malignancy
- •Prior organ transplantation including allogenic stem-cell transplantation
- •Current use of immunosuppressive medication, EXCEPT for the following:
- •intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
Arms & Interventions
Avelumab (Bavencio)
This is a single arm, and open label study. All the subjects recruited will receive Avelumab.
Intervention: Avelumab
Outcomes
Primary Outcomes
overall radiographic response
Time Frame: 6 months
overall radiographic response at six-month will be determined by iRECIST
Secondary Outcomes
- New metastasis-free survival(up to 2 years)
- Best radiographic response(up to 2 years)
- Frequency of adverse events(up to 2 years)
- Heath-related quality of life(up to 2 years)
- Progression-free survival(up to 2 years)
- Overall survival(up to 2 years)