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

NCT ID: NCT05183958

Last Updated: 2022-01-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-31
• Study Completion Date: 2025-12-01

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 .

Conditions

Esophageal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Radiotherapy group

Intervention Type: 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;

Camrelizumab

Intervention Type: DRUG

4 cycles for combined therapy. Camrelizumab maintenance.

Chemotherapy

Intervention Type: DRUG

4 cycles for combined therapy.

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.

Group Type: PLACEBO_COMPARATOR

Camrelizumab

Intervention Type: DRUG

4 cycles for combined therapy. Camrelizumab maintenance.

Chemotherapy

Intervention Type: DRUG

4 cycles for combined therapy.

Interventions

Radiotherapy group

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;

Intervention Type: RADIATION

Camrelizumab

4 cycles for combined therapy. Camrelizumab maintenance.

Intervention Type: DRUG

Chemotherapy

4 cycles for combined therapy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years old and ≤75 years old, regardless of gender;

2. Histologically or cytologically confirmed recurrent or metastatic esophageal squamous cell carcinoma;

3. 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;

4. 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;

5. 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);

6. 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;

7. ECOG PS score is 0～1;

8. For non-surgically sterilized female patients of childbearing age, the serum or urine HCG test must be negative within 72 hours before randomization;

9. 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;

10. Have not received immunotherapy or biological therapy before;

11. Hemoglobin ≥90g/L, platelets ≥10×10 9 /L, absolute neutrophil count ≥1.5×10 9 /L;

12. Serum creatinine ≤ 1.5 times UNL;

13. Serum bilirubin≤1.5×UNL, AST (SGOT) and ALT (SGPT)≤2.5×UNL, alkaline phosphatase≤5×UNL;

14. Coagulation function: INR≤1.5 × ULN; if the patient is receiving anticoagulation therapy, PT or APTT is within the acceptable range of treatment;

15. There was no history of interstitial pneumonia or previous interstitial pneumonia.

Exclusion Criteria

1. 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;

2. Patients have received radiotherapy in the past, and the tumor in the irradiation field has progressed;

3. BMI<18.5kg/m 2 , or weight loss >10% within 2 months before screening ;

4. With brain metastases;

5. With metastasis of the meninges, pleura or pericardium;

6. Esophageal perforation and active esophageal bleeding, with invasion of trachea and large blood vessels in the thoracic cavity;

7. Those who confirmed tumor progression during systemic treatment (RECIST 1.1 standard);

8. Severe symptoms of dysphagia caused by tumor compression require immediate radiotherapy intervention to relieve the obstruction;

10. 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;

11. Patients with severe lung disease, interstitial pneumonia, or previous history of interstitial pneumonia:

12. 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);

13. 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);

14. Suffered from an active infection requiring systemic treatment 14 days before the first administration;

15. 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;

16. Patients with other malignant lesions, except for curable skin cancer (non-melanoma), cervical carcinoma in situ or malignant disease cured ≥ 5 years;

17. Patients who cannot understand the test requirements or may not comply with the test requirements;

18. The investigator believes that some obvious diseases should be excluded from this study;

19. The dose limit of radiotherapy cannot meet the limit requirement set by this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhejiang Provincial People's Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Wenzhou Medical Univercity

UNKNOWN

Sponsor Role: collaborator

Jinhua Municipal Central Hospital

OTHER

Sponsor Role: collaborator

Lishui Municipal Central Hospital

OTHER_GOV

Sponsor Role: collaborator

The Affiliated People's hospital of Ningbo Univercity

OTHER

Sponsor Role: collaborator

Huizhou Municipal Central Hospital

OTHER

Sponsor Role: collaborator

People's Hospital of Quzhou

OTHER

Sponsor Role: collaborator

Sun Yet-sen Cancer Center

UNKNOWN

Sponsor Role: collaborator

Zhejiang Cancer Hospital

OTHER

Sponsor Role: lead

Responsible Party

ji yongling

Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

yongling Ji, MD

Role: PRINCIPAL_INVESTIGATOR

Zhejiang Cancer Hospital

Xianghui Du, MD

Role: PRINCIPAL_INVESTIGATOR

Zhejiang Cancer Hospital

Ming Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yet-sen Cancer Center

Locations

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Countries

China

Central Contacts

yongling Ji, MD

Role: CONTACT

wangjin@zjcc.org.cn

13958085251

jin Wang, Master

Role: CONTACT

Jiyl@zjcc.org.cn

18858165856

Other Identifiers

IRB-2021-389

Identifier Type: -

Identifier Source: org_study_id