Thalidomide Prevention or Treatment of Camrelizumab-induced Reactive Cutaneous Capillary Endothelial Proliferation (RCCEP)

NCT ID: NCT06231680

Last Updated: 2024-03-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-19
• Study Completion Date: 2025-09-30

Brief Summary

To explore the dose and safety of thalidomide for the prevention and treatment of camrelizumab-induced reactive cutaneous capillary endothelial proliferation (RCCEP)

Detailed Description

1. To increase the evidence of thalidomide for the prevention of RCCEP, the investigators will explore the dose of thalidomide for the prevention of RCCEP in participants with esophageal squamous cell carcinoma and non-small cell lung cancer who were scheduled to receive camrelizumab combined with platinum-based chemotherapy;

2. To increase the evidence of thalidomide for the treatment of RCCEP, the investigators will explore the dose of thalidomide for the treatment of ≥G2 RCCEP in participants with esophageal squamous cell carcinoma and non-small cell lung cancer with camrelizumab

Conditions

Lung Cancer, Nonsmall Cell; Esophageal Carcinoma

Study Design

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

Study Groups

Prevention Cohort 1 Group A

Camrelizumab + chemotherapy+Thalidomide(50mg)

Group Type: EXPERIMENTAL

Camrelizumab

Intervention Type: DRUG

Camrelizumab 200mg intravenous (IV) on Day 1 of each 21-day cycle，until progression or unacceptable toxicity

Thalidomide 50mg

Intervention Type: DRUG

Thalidomide 50mg，po qd；

Chemotherapy

Intervention Type: DRUG

Platinum-based chemotherapy:

1. Esophageal squamous cell carcinoma: cisplatin/carboplatin/nedaplatin/lobaplatin+ paclitaxel/albumin-bound paclitaxel/fluorouracil on Day 1 of each 21-day cycle for 4-6 cycles;

2. Non-small cell lung cancer (non-squamous cell carcinoma): pemetrexed plus carboplatin/cisplatin on Day 1 of each 21-day cycle for 4-6 cycles，pemetrexed every three weeks (Q3W) maintenance for the remainder of the study or until documented PD;

3. Non-small cell lung cancer (squamous cell carcinoma) : paclitaxel/albumin-bound paclitaxel + carboplatin/cisplatin on Day 1 of each 21-day cycle for 4-6 cycles.

Prevention Cohort 1 Group B

Camrelizumab + chemotherapy+Thalidomide(100mg)

Group Type: EXPERIMENTAL

Camrelizumab

Intervention Type: DRUG

Camrelizumab 200mg intravenous (IV) on Day 1 of each 21-day cycle，until progression or unacceptable toxicity

Thalidomide 100mg

Intervention Type: DRUG

Thalidomide 100mg，po qd；

Chemotherapy

Intervention Type: DRUG

Platinum-based chemotherapy:

1. Esophageal squamous cell carcinoma: cisplatin/carboplatin/nedaplatin/lobaplatin+ paclitaxel/albumin-bound paclitaxel/fluorouracil on Day 1 of each 21-day cycle for 4-6 cycles;

2. Non-small cell lung cancer (non-squamous cell carcinoma): pemetrexed plus carboplatin/cisplatin on Day 1 of each 21-day cycle for 4-6 cycles，pemetrexed every three weeks (Q3W) maintenance for the remainder of the study or until documented PD;

3. Non-small cell lung cancer (squamous cell carcinoma) : paclitaxel/albumin-bound paclitaxel + carboplatin/cisplatin on Day 1 of each 21-day cycle for 4-6 cycles.

Treatment Cohort 2 Group A

Thalidomide(100mg)

Group Type: EXPERIMENTAL

Thalidomide 100mg

Intervention Type: DRUG

Thalidomide 100mg，po qd；

Treatment Cohort 2 Group B

Thalidomide(200mg)

Group Type: EXPERIMENTAL

Thalidomide 200mg

Intervention Type: DRUG

Thalidomide 200mg，po qd；

Interventions

Camrelizumab

Camrelizumab 200mg intravenous (IV) on Day 1 of each 21-day cycle，until progression or unacceptable toxicity

Intervention Type: DRUG

Thalidomide 50mg

Thalidomide 50mg，po qd；

Intervention Type: DRUG

Thalidomide 100mg

Thalidomide 100mg，po qd；

Intervention Type: DRUG

Thalidomide 200mg

Thalidomide 200mg，po qd；

Intervention Type: DRUG

Chemotherapy

Platinum-based chemotherapy:

1. Esophageal squamous cell carcinoma: cisplatin/carboplatin/nedaplatin/lobaplatin+ paclitaxel/albumin-bound paclitaxel/fluorouracil on Day 1 of each 21-day cycle for 4-6 cycles;

2. Non-small cell lung cancer (non-squamous cell carcinoma): pemetrexed plus carboplatin/cisplatin on Day 1 of each 21-day cycle for 4-6 cycles，pemetrexed every three weeks (Q3W) maintenance for the remainder of the study or until documented PD;

3. Non-small cell lung cancer (squamous cell carcinoma) : paclitaxel/albumin-bound paclitaxel + carboplatin/cisplatin on Day 1 of each 21-day cycle for 4-6 cycles.

Intervention Type: DRUG

Other Intervention Names

SHR-1210; Thalidomide; Thalidomide; Thalidomide; Platinum-based chemotherapy

Eligibility Criteria

Inclusion Criteria

• Prevention cohort 1:

1. Histopathology or cytology confirmed advanced non-small cell lung cancer or esophageal squamous cell carcinoma; no previous systemic therapy (patients who had progressed ≥6 months after [neo] adjuvant therapy were eligible).

2. A treatment regimen of Camrelizumab combined with platinum-containing chemotherapy is planned.

3. ECOG: 0-1;

4. Age ≥18 years old;

5. Have a life expectancy of at least 12 weeks;

6. No prior therapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (including any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

7. Can swallow pills normally;

8. Adequate organ and bone marrow function：Standard of blood routine examination (without transfusion within 14 days) : Hemoglobin (HB) ≥80 g/L; Neutrophil absolute value (ANC) ≥1.5×10^9/L; Platelet (PLT) ≥90×10^9/L;Biochemical examination should meet the following criteria: Total bilirubin (TBIL) ≤1.5 times the upper limit of normal value (ULN); Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3×ULN; Serum creatinine (Cr) ≤1.5 ULN;

9. Female Subjects of childbearing potential must have a negative serum pregnancy test within 72 hours before the first dose and must be willing to use very efficient barrier methods of contraception for the course of the study through 2 months after the last dose of study treatment. Male Subjects with a female partner(s) of child-bearing potential must be willing to use very efficient barrier methods of contraception for the course of the study through 2 months after the last dose of study treatment;

10. Subjects has voluntarily agreed to participate by giving written informed consent/assent for the trial.

• Treatment cohort 2:

1. Histopathology or cytology confirmed advanced lung cancer or esophageal carcinoma;

2. Subjects had≥G2 grade RCCEP for the first time after treatment with a Camrelizumab based regimen;

3. ECOG: 0-2;

4. Age ≥18 years old;

5. Have a life expectancy of at least 12 weeks;

6. Can swallow pills normally;

7. No ongoing grade 3 or higher adverse events except for RCCEP (according to CTCAE version 5.0).

8. Female Subjects of childbearing potential must have a negative serum pregnancy test within 72 hours before the first dose and must be willing to use very efficient barrier methods of contraception for the course of the study through 2 months after the last dose of study treatment. Male Subjects with a female partner(s) of child-bearing potential must be willing to use very efficient barrier methods of contraception for the course of the study through 2 months after the last dose of study treatment;

9. Subjects have voluntarily agreed to participate by giving written informed consent/assent for the trial.

Exclusion Criteria

• Prevention cohort 1:

1. Known allergy to the investigational drug or excipient, history of severe hypersensitivity reactions to other monoclonal antibodies.

2. Subjects with a condition requiring systemic treatment with other immunosuppressive medications within 14 days of first administration of study treatment.

3. Subjects had administration of a live, attenuated vaccine within 4 weeks of the first dose of study treatment or anticipation that such a live attenuated vaccine will be required during the study.

4. Advanced patients who have symptoms, have spread to the internal organs, and are at risk of developing life-threatening complications in the short term;

5. Subjects with a history of interstitial lung disease, or other disease may interfere with the detection or treatment of suspected drug-related lung toxicity.

6. Subjects with active, known or suspected autoimmune disease. Subjects in conditions not expected to recur in the absence of an external trigger, or not requiring systemic treatment are permitted to enroll.

7. HIV infection; Combined hepatitis B and hepatitis C co-infection

8. Subjects with active CNS metastases are excluded.

9. Subjects with clinically significant cardiovascular and cerebrovascular diseases.

10. Coagulation abnormalities, with bleeding tendency or are receiving thrombolytic or anticoagulant therapy;

11. Disposition evidence of hemoptysis in 2 months (bright red blood, 1/2 teaspoon).

12. History of hemorrhage within 3 months prior to the start of study treatment or clear tendency of hemorrhage

13. Thrombosis or thromboembolic event within 6 months prior to the start of study treatment;

14. Active infection (CTCAE> Grade 2)

15. Subjects had or plan to have allogeneic bone marrow transplantation or solid organ transplant.

16. Subjects are currently participating and receiving study therapy or had participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks or 5 half-value period life of the agent, before the first dose of trial treatment.

17. Subjects have known psychiatric or substance abuse disorder

18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.

• Treatment cohort 2:

1. Known allergy to the investigational drug or excipient

2. Advanced patients who have symptoms, have spread to the internal organs, and are at risk of developing life-threatening complications in the short term;

3. Subjects with a history of interstitial lung disease, or other disease may interfere with the detection or treatment of suspected drug-related lung toxicity.

4. HIV infection; Combined hepatitis B and hepatitis C co-infection

5. Active infection (CTCAE> Grade 2)

6. Subjects have known psychiatric or substance abuse disorder

7. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator

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

Sponsors

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role: collaborator

Henan Cancer Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Ying Liu

Deputy Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ying Liu, MD

Role: PRINCIPAL_INVESTIGATOR

Henan Cancer Hospital

Yu Yao, MD

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital Xi'an Jiaotong University

Locations

Ying Liu

Zhengzhou, Henan, China

Site Status: RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Site Status: NOT_YET_RECRUITING

Countries

China

Central Contacts

Ying Liu, MD

Role: CONTACT

yaya7207@126.com

+86 137 8360 4602

Facility Contacts

Ying Liu, MD

Role: primary

yaya7207@126.com

+8613783604602

Yu Yao, MD

Role: primary

Other Identifiers

MA-RCCEP-II-001

Identifier Type: -

Identifier Source: org_study_id