A Multicenter, Randomized Controlled, Phase II Clinical Study of First-line Chemotherapy and Camrelizumab With or Without Radiotherapy in the Treatment of Oligometastatic Esophageal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Chemotherapy
- Conditions
- Esophageal Cancer
- Sponsor
- Zhejiang Cancer Hospital
- Enrollment
- 118
- Locations
- 1
- Primary Endpoint
- Progression-free survival (PFS)
- Status
- Not yet recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
A multi-center, open, randomized controlled, phase II clinical study to evaluate the efficiency and safety of chemotherapy and immunotherapy combined with locol radiotharepy in treatment of patients with oligometastatic esophageal carcinoma.
Detailed Description
This is a multi-center, open, randomized controlled, phase II clinical study to evaluate the efficiency and safety of chemotherapy and immunotherapy combined with locol radiotharepy in treatment of patients with oligometastatic esophageal carcinoma.For patients required that recurrent or metastatic esophageal cancer, no more than 3 metastatic organs and no more than 5 metastatic lesions. First, all patients receive chemotherapy (the regimen includes paclitaxel and platinum drugs; or cisplatin, pentafluorouracil (5-fluorouracil) ) and other standard first-line chemotherapeutics, combined with Camrelizumab for 4 cycles, and the patients who have not progressed were randomly divided into non-radiotherapy group (control group) and combined radiotherapy group (experimental group) at 1:1 ratio. The experimental group received radiotherapy of the lesion within 8 weeks after the end of chemotherapy and immunotherapy. At least one lesion (both primary and metastatic lesions) was required to be irradiated. Stereotactic body radiotherapy (SBRT, 8Gy/time, 3 -5 times, if other segmentation schemes are used, recommend BED10 \>60Gy) or conventional fractional radiotherapy (parts that are not suitable for SBRT, the total dose is more than 30Gy); the primary lesion should be treated with conventional fractional radiotherapy with a dose of 4000cGy or more;The radiotherapy of the primary lesions and metastases focus is carried out at the same time or sequentially, and immunotherapy shall be started within 8 weeks after the end of all radiotherapy. The control group continued Camrelizumab after 3 weeks of the 4 cycles of chemotherapy combined with immunotherapy. The maintenance immunotherapy of the two groups was: Camrelizumab 200mg Q3W, until PD or toxicity is intolerable or up to 24 months. The endpoint are PFS, OS, ORR and toxicity of the two groups .
Investigators
ji yongling
Physician
Zhejiang Cancer Hospital
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years old and ≤75 years old, regardless of gender;
- •Histologically or cytologically confirmed recurrent or metastatic esophageal squamous cell carcinoma;
- •Non-regional lymph node metastasis, such as upper neck, retroperitoneal or axillary lymph node metastasis; or distant metastasis, but no more than 3 metastatic organs, and no more than 5 lesions;
- •Patients who have not received other systems of anti-tumor treatment; the patients who have received neoadjuvant/adjuvant and radical concurrent radiochemotherapy, and the last treatment time or progress time exceeds 6 months;
- •Patients who have not progressed after receiving 4 courses of chemotherapy combined with PD-1 immune checkpoint inhibitor treatment (according to the RECIST 1.1 evaluation standard);
- •There are measurable lesions according to the RECIST 1.1 standard (cavity structures such as the esophagus cannot be used as measurable lesions), and the measurable lesions should not have received local treatment such as radiotherapy;
- •ECOG PS score is 0～1;
- •For non-surgically sterilized female patients of childbearing age, the serum or urine HCG test must be negative within 72 hours before randomization;
- •Volunteer to participate in clinical research: fully understand and know the research and sign the Informed Consent Form (ICF); willing to follow and have the ability to complete all trial procedures;
- •Have not received immunotherapy or biological therapy before;
Exclusion Criteria
- •In addition to the systemic treatment recommended by this program, patients have received other immune checkpoint inhibitor treatments such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibodies in the past, or any other antibodies or drugs with specific targets for T cell costimulation or checkpoint pathways;
- •Patients have received radiotherapy in the past, and the tumor in the irradiation field has progressed;
- •BMI\<18.5kg/m 2 , or weight loss \>10% within 2 months before screening ;
- •With brain metastases;
- •With metastasis of the meninges, pleura or pericardium;
- •Esophageal perforation and active esophageal bleeding, with invasion of trachea and large blood vessels in the thoracic cavity;
- •Those who confirmed tumor progression during systemic treatment (RECIST 1.1 standard);
- •Severe symptoms of dysphagia caused by tumor compression require immediate radiotherapy intervention to relieve the obstruction;
- •Systemic treatment toxicity did not return to ≤ CTCAE level 1 (except for hair loss) or the level specified by the inclusion/exclusion criteria;
- •Subjects have cardiovascular diseases or clinical symptoms that are not well controlled, including but not limited to: (1) Heart failure above NYHA II; (2) Unstable angina; (3) Myocardial infarction within 1 year; ( 4) Clinically significant supraventricular tachycardia or ventricular arrhythmia without clinical intervention, or poor control after clinical intervention;
Arms & Interventions
Combined radiotherapy group
Chemotherapy :TP program (paclitaxel 175mg/m 2 d1, carboplatin AUC=5 d1 IV Q3W; or paclitaxel 175mg/m 2 d1, cisplatin 75mg/m 2 d1, or paclitaxel 175mg/m 2 d1, cis Platinum 25mg/m 2 d1-3 IV (Q3W, up to 4 cycles). Fluorouracil + cisplatin, cisplatin 80 mg/m 2 d1 IV and 5-Fu 800 mg/m 2 continuous IV d1-5 Q3W (up to 4 cycles).Or cisplatin 50mg/m 2 IV d1; LV 200mg/m 2 IV d1; 5-Fu 2000mg/m 2 24 hours continuous IV d1; or cisplatin 80mg/m 2 IV d1, capecitabine 1000mg/m 2 PO BID d1-14. Camrelizumab :200mg every 3 weeks,maximum 6 cycles. The experimental group received radiotherapy of the lesion within 8 weeks after the end of chemotherapy and immunotherapy. Immunotherapy shall be started within 8 weeks after the end of all radiotherapy. The maintenance immunotherapy of the two groups was: Camrelizumab 200mg Q3W, until PD or toxicity is intolerable or up to 24 months.
Intervention: Chemotherapy
Combined radiotherapy group
Chemotherapy :TP program (paclitaxel 175mg/m 2 d1, carboplatin AUC=5 d1 IV Q3W; or paclitaxel 175mg/m 2 d1, cisplatin 75mg/m 2 d1, or paclitaxel 175mg/m 2 d1, cis Platinum 25mg/m 2 d1-3 IV (Q3W, up to 4 cycles). Fluorouracil + cisplatin, cisplatin 80 mg/m 2 d1 IV and 5-Fu 800 mg/m 2 continuous IV d1-5 Q3W (up to 4 cycles).Or cisplatin 50mg/m 2 IV d1; LV 200mg/m 2 IV d1; 5-Fu 2000mg/m 2 24 hours continuous IV d1; or cisplatin 80mg/m 2 IV d1, capecitabine 1000mg/m 2 PO BID d1-14. Camrelizumab :200mg every 3 weeks,maximum 6 cycles. The experimental group received radiotherapy of the lesion within 8 weeks after the end of chemotherapy and immunotherapy. Immunotherapy shall be started within 8 weeks after the end of all radiotherapy. The maintenance immunotherapy of the two groups was: Camrelizumab 200mg Q3W, until PD or toxicity is intolerable or up to 24 months.
Intervention: Radiotherapy group
Combined radiotherapy group
Chemotherapy :TP program (paclitaxel 175mg/m 2 d1, carboplatin AUC=5 d1 IV Q3W; or paclitaxel 175mg/m 2 d1, cisplatin 75mg/m 2 d1, or paclitaxel 175mg/m 2 d1, cis Platinum 25mg/m 2 d1-3 IV (Q3W, up to 4 cycles). Fluorouracil + cisplatin, cisplatin 80 mg/m 2 d1 IV and 5-Fu 800 mg/m 2 continuous IV d1-5 Q3W (up to 4 cycles).Or cisplatin 50mg/m 2 IV d1; LV 200mg/m 2 IV d1; 5-Fu 2000mg/m 2 24 hours continuous IV d1; or cisplatin 80mg/m 2 IV d1, capecitabine 1000mg/m 2 PO BID d1-14. Camrelizumab :200mg every 3 weeks,maximum 6 cycles. The experimental group received radiotherapy of the lesion within 8 weeks after the end of chemotherapy and immunotherapy. Immunotherapy shall be started within 8 weeks after the end of all radiotherapy. The maintenance immunotherapy of the two groups was: Camrelizumab 200mg Q3W, until PD or toxicity is intolerable or up to 24 months.
Intervention: Camrelizumab
Non-radiotherapy group
Chemotherapy :TP program (paclitaxel 175mg/m 2 d1, carboplatin AUC=5 d1 IV Q3W; or paclitaxel 175mg/m 2 d1, cisplatin 75mg/m 2 d1, or paclitaxel 175mg/m 2 d1, cis Platinum 25mg/m 2 d1-3 IV (Q3W, up to 4 cycles). Fluorouracil + cisplatin, cisplatin 80 mg/m 2 d1 IV and 5-Fu 800 mg/m 2 continuous IV d1-5 Q3W (up to 4 cycles).Or cisplatin 50mg/m 2 IV d1; LV 200mg/m 2 IV d1; 5-Fu 2000mg/m 2 24 hours continuous IV d1; or cisplatin 80mg/m 2 IV d1, capecitabine 1000mg/m 2 PO BID d1-14. Camrelizumab :200mg every 3 weeks,maximum 6 cycles. The control group continued Camrelizumab after 3 weeks of the 4 cycles of chemotherapy combined with immunotherapy. The maintenance immunotherapy of the two groups was: Camrelizumab 200mg Q3W, until PD or toxicity is intolerable or up to 24 months.
Intervention: Camrelizumab
Non-radiotherapy group
Chemotherapy :TP program (paclitaxel 175mg/m 2 d1, carboplatin AUC=5 d1 IV Q3W; or paclitaxel 175mg/m 2 d1, cisplatin 75mg/m 2 d1, or paclitaxel 175mg/m 2 d1, cis Platinum 25mg/m 2 d1-3 IV (Q3W, up to 4 cycles). Fluorouracil + cisplatin, cisplatin 80 mg/m 2 d1 IV and 5-Fu 800 mg/m 2 continuous IV d1-5 Q3W (up to 4 cycles).Or cisplatin 50mg/m 2 IV d1; LV 200mg/m 2 IV d1; 5-Fu 2000mg/m 2 24 hours continuous IV d1; or cisplatin 80mg/m 2 IV d1, capecitabine 1000mg/m 2 PO BID d1-14. Camrelizumab :200mg every 3 weeks,maximum 6 cycles. The control group continued Camrelizumab after 3 weeks of the 4 cycles of chemotherapy combined with immunotherapy. The maintenance immunotherapy of the two groups was: Camrelizumab 200mg Q3W, until PD or toxicity is intolerable or up to 24 months.
Intervention: Chemotherapy
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: Up to 24 month
PFS, defined as the time from randomization to the first occurrence of disease progression.
Secondary Outcomes
- Objective Response Rate (ORR)(Up to 24 month)
- Overall survival (OS)(Up to 24 month)
- Adverse Events (AEs)(Up to 24 month)