Efficacy of Neoadjuvant PD-1 Blockade Plus Chemotherapy for Esophageal Squamous Cell Carcinoma

NCT04225364 | Completed Phase 2 DMC

• 1 other identifier: NIC-ESCC2019
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the efficacy of Camrelizumab plus concurrent chemotherapy as neoadjuvant approach for patients with opearble esophageal squamous cell carcinoma. In addition, potential clinical utility of ctDNA in monitoring tumor burden and dynamics of tumor clonality during neoadjuvant immunotherapy will be assessed as well. At the same time, CD8 and PD-L1 will also be used as monitoring indicators.

Conditions

Esophageal Squamous Cell Carcinoma; Immunotherapy

Keywords

neoadjuvant immunotherapy; Stage II-IVA; esophageal squamous cell carcinoma; ctDNA; neoadjuvant chemotherapy

Outcome Measures

Primary Outcomes (1)

• Pathologic complete remission (PCR)

  Primary tumor or lymph node surgery specimen pathological examination without residual tumor cell

  4 weeks after surgery

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  At the end of Cycle 2 (each cycle is 21 days)

• 2-year progression-free survival (PFS)

  every 2 months (up to 24 months)

• Progression-free survival (PFS)

  every 2 months (up to 24 months)

• Overall survival (OS)

  every 2 months (up to 24 months)

Other Outcomes (4)

• safety of neoadjuvant PD-1 Blockade Plus Chemotherapy

  Every 3 weeks (up to 3 months after surgery)

• Evaluation of molecular features and ctDNA changing in pre, per and post-treatment plasma

  every 2 months (up to 12 months)

• Evaluation of Immunomicroenvironment changing in pre, per and post-treatment plasma

  every 2 months (up to 12 months)

Study Arms (1)

camrelizumab plus concurrent chemotherapy

EXPERIMENTAL

Neoadjuvant immunotherapy, PD-1, plus concurrent chemotherapy（albumin-bound paclitaxel + Cisplatin） will be applied to patients with operable esophageal squamous cell carcinoma before surgery.

Drug: camrelizumab; Drug: Paclitaxel for injection (albumin-bound); Drug: Cisplatin

Interventions

camrelizumab DRUG

Participants will receive camrelizumab, 200mg, intravenously over 30 - 60 minutes, day 1 of every 3 weeks for 6 weeks. Discontinuation will be considered due to toxicity, withdrawal of consent, or end of study. Every 3-week treatment period was considered to be a cycle.

Also known as: SHR-1210

camrelizumab plus concurrent chemotherapy

Paclitaxel for injection (albumin-bound) DRUG

Paclitaxel for injection (albumin-bound): 260mg/m2(in total), ivgtt d1, d8, q3w，for 2 cycle

Also known as: paclitaxel

camrelizumab plus concurrent chemotherapy

Cisplatin DRUG

75mg/m2(in total), ivgtt d1-d3, q3w, for 2 cycles

Also known as: CDDP

camrelizumab plus concurrent chemotherapy

Eligibility Criteria

• Age: 17 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged ≥18 years, ≤70 years.
• Gastroscope/ultrasound gastroscopy biopsy, Histologically or cytologically confirmed esophageal squamous cell carcinoma. Clinically diagnosed as II-IVA esophageal squamous cell carcinoma (cT2N1-3M0/cT3N0-3M0/cT4N0-3M0).
• Non-Cervical Esophageal Cancer
• Previously received no systemic or topical treatment for esophageal cancer, at least one measurable lesion for neoadjuvant treatment imaging evaluation according to RECIST 1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Estimated survival time ≥ 12 months;
• Subjects had no major organ dysfunction, and the investigators assessed thyroid, lung, liver, kidney function, and cardiac function as normal.
• Women of childbearing age must have taken reliable Contraception or have the negative predictive value of urine/ serum pregnancy test within 7 days prior to enrollment. They are also willing to use appropriate methods of contraception during the trial and 8 weeks after the last administration of the test drugs. For men, They must agree to use contraception or surgical sterilization during the trial and 8 weeks after the last administration of the test drug.
• Subjects voluntarily joined the study and signed informed consent. patients who accept blood sample collection at multiple time points. Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.

You may not qualify if:

• Have a history of gastrectomy or have surgical contraindications
• The investigator assessed that the patient had other serious illnesses that may affect follow-up and short-term survival;
• There are any active autoimmune diseases or a medical history of autoimmune (including, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, thyroid function Decreased. Subjects with vitiligo or adults who have had childhood asthma but have fully relieved without any intervention may be included. However, subjects who require bronchodilators for medical intervention cannot be included.)
• Cardiac clinical symptoms or diseases that are not well controlled, such as: a. Heart Failure NYHA \> Class Ⅱ, b. unstable angina, c. myocardial infarction within 1 year; d. Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
• Subjects with congenital or acquired immunodeficiency (such as HIV-infected), or active hepatitis (hepatitis B reference: HBsAg-positive, HBV DNA ≥ 2000 IU/ml or copy number ≥ 104/ml; hepatitis C reference: HCV antibody-positive.)
• Uncontrollable history of diabetes;
• Patients who have used other clinical trial study drugs within 4 weeks prior to the first dose.
• Severe allergic reactions to monoclonal antibodies or allergy to paclitaxel or human albumin.
• Peripheral blood neutrophil count is less than 1500/mm3
• Patients who have received or are undergoing other chemotherapy, radiation therapy or targeted therapy.
• According to the investigator's assessment, there are other factors that may lead to the termination of the study, such as other serious diseases (including mental illness) requiring combined treatment. Any other condition and social/psychological problems, etc., the investigator judged that the patient was not suitable for participation in the study.

Sponsors & Collaborators

• Guangzhou Institute of Respiratory Disease: lead
• BGI-Shenzhen: collaborator
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

Study Sites (1)

Jingpei Li

Guangzhou, Guangdong, China

Location

Related Publications (3)

• Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. doi: 10.1016/S0140-6736(17)31827-5. Epub 2017 Oct 6.

  PMID: 28993052 BACKGROUND

• Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-1098. doi: 10.1016/S1470-2045(15)00040-6. Epub 2015 Aug 5.

  PMID: 26254683 BACKGROUND

• Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. doi: 10.1200/JCO.2018.79.1483. Epub 2018 Aug 8.

  PMID: 30089078 BACKGROUND

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

camrelizumab; Paclitaxel; Injections; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Drug Administration Routes; Drug Therapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Jun liu, Ph.D, M.D

  The First Affiliated Hospital of Guangzhou Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical professor, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University

Model Details: Patients with II-IVA stage with pathologically diagnosed squamous cell lung carcinoma will be enrolled in this study. Camrelizumab plus chemotherapy will be administrated intravenously per 3 weeks at the dosage of 200mg. Contrast-CT evaluation and peripheral blood collected will be performed at pre-neoadjuvant therapy and pre-operation. 6 weeks after neoadjuvant therapy, participants who meet the indication will be assigned to operation. Another peripheral blood sample will be harvested 3-4 weeks after operation.

Study Record Dates

• First Submitted: December 23, 2019
• First Posted: January 13, 2020
• Study Start: January 17, 2020
• Primary Completion: January 15, 2021
• Study Completion: January 31, 2021
• Last Updated: February 2, 2021

Record last verified: 2021-01

Locations

CN (1)