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

A Prospective, Randomized Clinical Study of the Prevention or Treatment of Camrelizumab-induced Reactive Cutaneous Capillary Endothelial Proliferation (RCCEP) With Thalidomide

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

Study Overview

• Status: Recruiting
• Conditions: Esophageal Carcinoma; Lung Cancer, Nonsmall Cell
• Intervention / Treatment: Drug: Camrelizumab; Drug: Thalidomide 50mg; Drug: Chemotherapy; Drug: Thalidomide 100mg; Drug: Thalidomide 200mg

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

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ying Liu, MD; Phone Number: +86 137 8360 4602; Email: yaya7207@126.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Ying Liu
      • Principal Investigator: Ying Liu, MD
      • Contact: Ying Liu, MD; Phone Number: +8613783604602; Email: yaya7207@126.com
  • Shaanxi
    • Xi'an, Shaanxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Principal Investigator: Yu Yao, MD
      • Contact: Yu Yao, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prevention Cohort 1 Group A; Camrelizumab + chemotherapy+Thalidomide(50mg)	Drug: Camrelizumab; Camrelizumab 200mg intravenous (IV) on Day 1 of each 21-day cycle，until progression or unacceptable toxicity; Other Names: SHR-1210; Drug: Thalidomide 50mg; Thalidomide 50mg，po qd； Other Names: Thalidomide; Drug: Chemotherapy; Platinum-based chemotherapy: 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;; 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;; 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.; Other Names: Platinum-based chemotherapy
Experimental: Prevention Cohort 1 Group B; Camrelizumab + chemotherapy+Thalidomide(100mg)	Drug: Camrelizumab; Camrelizumab 200mg intravenous (IV) on Day 1 of each 21-day cycle，until progression or unacceptable toxicity; Other Names: SHR-1210; Drug: Chemotherapy; Platinum-based chemotherapy: 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;; 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;; 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.; Other Names: Platinum-based chemotherapy; Drug: Thalidomide 100mg; Thalidomide 100mg，po qd； Other Names: Thalidomide
Experimental: Treatment Cohort 2 Group A; Thalidomide(100mg)	Drug: Thalidomide 100mg; Thalidomide 100mg，po qd； Other Names: Thalidomide
Experimental: Treatment Cohort 2 Group B; Thalidomide(200mg)	Drug: Thalidomide 200mg; Thalidomide 200mg，po qd； Other Names: Thalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of RCCEP	Incidence rate of RCCEP	2 years
RCCEP response rate at 3 weeks	RCCEP response rate at 3 weeks	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of ≥G3 grade RCCEP	Incidence rate of ≥G3 grade RCCEP	2 years
Median time to RCCEP	Median time to RCCEP	2 years
Incidence rate of RCCEP at 6 weeks	Incidence rate of RCCEP at 6 weeks	6 weeks
Incidence rate of RCCEP at 9 weeks	Incidence rate of RCCEP at 9 weeks	9 weeks
Median time to response of RCCEP	Median time to response of RCCEP	2 years
Thalidomide treatment-related adverse events	Thalidomide treatment-related adverse events	2 years

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Collaborators: First Affiliated Hospital Xi'an Jiaotong University
• Investigators: Principal Investigator: Ying Liu, MD, Henan Cancer Hospital; Principal Investigator: Yu Yao, MD, First Affiliated Hospital Xi'an Jiaotong University

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2024
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: November 7, 2023
• First Submitted That Met QC Criteria: January 26, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Head and Neck Neoplasms; Esophageal Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Esophageal Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide
• Other Study ID Numbers: MA-RCCEP-II-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No