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

NCT05183958 | Unknown Phase 2

• 1 other identifier: IRB-2021-389
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS, defined as the time from randomization to the first occurrence of disease progression.

  Up to 24 month

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to 24 month

• Overall survival (OS)

  Up to 24 month

• Adverse Events (AEs)

  Up to 24 month

Other Outcomes (2)

• Disease Control Rate (DCR)

  Up to 24 month

• Duration of Response (DoR)

  Up to 24 month

Study Arms (2)

Combined radiotherapy group

EXPERIMENTAL

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.

Radiation: Radiotherapy group; Drug: Camrelizumab; Drug: Chemotherapy

Non-radiotherapy group

PLACEBO COMPARATOR

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.

Drug: Camrelizumab; Drug: Chemotherapy

Interventions

Radiotherapy group RADIATION

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;

Combined radiotherapy group

Camrelizumab DRUG

4 cycles for combined therapy. Camrelizumab maintenance.

Combined radiotherapy group; Non-radiotherapy group

Chemotherapy DRUG

4 cycles for combined therapy.

Combined radiotherapy group; Non-radiotherapy group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Hemoglobin ≥90g/L, platelets ≥10×10 9 /L, absolute neutrophil count ≥1.5×10 9 /L;
• Serum creatinine ≤ 1.5 times UNL;
• Serum bilirubin≤1.5×UNL, AST (SGOT) and ALT (SGPT)≤2.5×UNL, alkaline phosphatase≤5×UNL;
• Coagulation function: INR≤1.5 × ULN; if the patient is receiving anticoagulation therapy, PT or APTT is within the acceptable range of treatment;
• There was no history of interstitial pneumonia or previous interstitial pneumonia.

You may not qualify if:

• 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;
• 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;
• Patients with severe lung disease, interstitial pneumonia, or previous history of interstitial pneumonia:
• Autoimmune diseases (such as: systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease), but allow the following diseases to enter the next step of screening: type I diabetes, skin diseases that do not require systemic treatment ( Such as vitiligo, psoriasis);
• Patients have active hepatitis B (HBV DNA≥2000IU/L or 104copies/ml) or hepatitis C (hepatitis C antibody is positive, and HCV-RNA is higher than the detection limit of the analysis method);
• Suffered from an active infection requiring systemic treatment 14 days before the first administration;
• Patients with active pulmonary tuberculosis infection found through medical history or CT examination, or patients with a history of active pulmonary tuberculosis infection 1 year before enrollment, or patients with active pulmonary tuberculosis infection more than 1 year ago but without formal treatment;
• Patients with other malignant lesions, except for curable skin cancer (non-melanoma), cervical carcinoma in situ or malignant disease cured ≥ 5 years;

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead
• Zhejiang Provincial People's Hospital: collaborator
• The First Affiliated Hospital of Wenzhou Medical Univercity: collaborator
• Jinhua Municipal Central Hospital: collaborator
• Lishui Municipal Central Hospital: collaborator
• The Affiliated People's hospital of Ningbo Univercity: collaborator
• Huizhou Municipal Central Hospital: collaborator
• People's Hospital of Quzhou: collaborator
• Sun Yet-sen Cancer Center: collaborator

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

camrelizumab; Drug Therapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• yongling Ji, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Xianghui Du, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Ming Chen, MD

  Sun Yet-sen Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

yongling Ji, MD

CONTACT

13958085251; wangjin@zjcc.org.cn

jin Wang, Master

CONTACT

18858165856; Jiyl@zjcc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: January 11, 2022
• Study Start: December 31, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2025
• Last Updated: January 11, 2022

Record last verified: 2021-12

Locations

CN (1)