Short Course Neoadjuvant Chemo-radiotherapy Plus Toripalimab for Locally Advanced Resectble Squamous Cell Carcinoma of Esophagus

NCT05424432 | Unknown Phase 2

• 1 other identifier: SCALE-2
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

Adding PD-1 inhibitors to neoadjuvant chemoradiotherapy has shown promising results in locally advanced resectable esophageal squamous cell carcinoma (ESCC). However, there is a need to explore safer and more effective treatment doses and schedules. This is an open labeled, prospective, single-arm phase II trial to evaluate the safety and efficacy of the short course neoadjuvant chemo-radiotherapy plus Toripalimab for locally advanced resectble ESCC.

Conditions

Locally Advanced Esophageal Carcinoma

Keywords

esophageal carcinoma; short course neoadjuvant radiotherapy; Toripalimab; neoadjuvant chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response

  Pathologic complete response was defined as pT0N0M0 or pTisN0M0

  1 month after resection

Secondary Outcomes (6)

• Disease free survival

  3 years after resection

• 3-year overall survival

  3 years after enrollment

• Incidence of Treatment-related Adverse Events

  From the date of enrollment until surgery was applied during study period or up to at least 90 days after last dose

• Perioperative complication rate

  From date of surgery to 30 days later

• Health related quality of Life

  Measured before and after neoadjuvant therapy, before and 1, 3, 6, 9, 12 months after surgery.

Study Arms (1)

short course neoadjuvant chemoradiotherapy plus toripalimab

EXPERIMENTAL

Paclitaxel, carboplatin and toripalimab every 3 weeks for two cycles. Concurrent short course neoadjuvant radiotherapy (30 Gy in 12 fractions, 5 days per week, D3-D18). Surgery will be performed within 8-10 weeks after the completion of preoperative therapy described above.

Drug: Neoadjuvant Chemotherapy; Drug: Neoadjuvant Toripalimab; Radiation: Short Course Neoadjuvant Radiotherapy

Interventions

Neoadjuvant Chemotherapy DRUG

Paclitaxel (135 mg /m2) and carboplatin (AUC=5) every 3 weeks for two cycles (D1,D22)

short course neoadjuvant chemoradiotherapy plus toripalimab

Neoadjuvant Toripalimab DRUG

Toripalimab 240mg every 3 weeks for two cycles (D2,D23)

short course neoadjuvant chemoradiotherapy plus toripalimab

Short Course Neoadjuvant Radiotherapy RADIATION

30 Gy in 12 fractions, 1 fraction per day, 5 days per week, D3-D18

short course neoadjuvant chemoradiotherapy plus toripalimab

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able to provide written informed consent and understand and agree to follow the research requirements and evaluation schedule.
• Endoscopic biopsy of thoracic esophageal primary lesion histologically diagnosed as squamous cell carcinoma.
• Clinical stage T1-4aN+M0 or T3-4aN0M0 in the UICC-TNM classification 8th edition.
• The age is over 20 years old and under 75 on the enrollment date (including 20 and 75), including both female and male.
• PS 0-1.
• According to RECIST version 1.1, there were measurable or evaluable lesions.
• No medical history of treatment for cancer (No medical history of chemotherapy, radiotherapy and endocrine therapy, immune-therapy or other study drugs including treatment for other types of cancer).
• Bone marrow function: hemoglobin (Hb) \>=90g/L; white blood cell count (WBC) \>= lower limit of normal value; absolute neutrophil value (ANC) \>= 1.5x10\^9 /L; platelet count \>= 100x10\^9 / L;
• Renal function: Cr \<= 1.5 UNL, endogenous creatinine clearance rate (Ccr) \>= 60 ml/min（Cockcroft-Gault）;
• Liver function: total bilirubin \<= 1.5 ULN; ALT and AST \<= 2.5 ULN (patients with liver metastases can be relaxed to \<=5 ULN);
• Blood coagulation function: the international standardized ratio of prothrombin time \<= 1.5 ULN, and the partial thromboplastin time is within the normal range.
• Patients with hepatitis B virus (HBV) infection, inactive / asymptomatic HBV carriers, or patients with chronic or active HBV will be allowed to be enrolled if HBV DNA \< 500 IU / ml (or 2500 copies / ml) at screening. Patients with positive hepatitis C antibody will be allowed to be enrolled if HCV-RNA is negative during screening.Note: patients who can detect hepatitis B surface antigen (HBsAg) or HBV DNA should be treated with antiviral drugs for more than 2 weeks before enrollment, and the treatment should be continued for 6 months after the study drug treatment.
• Women of childbearing age (wocbp) should take the urine or serum pregnancy test, and the result of which should be negtive within ≤ 72 hours before treatment. For females, who have agreed with contraception from start of investigational drug administration to 5 months after last dose of investigational drug. For males who have agreed with contraception from start of investigational drug administration to 7 months after last dose of investigational drug.

You may not qualify if:

• Have received any treatment for esophageal squamous cell carcinoma in the past;
• Patients with evidence or high risk of gastrointestinal hemorrhage or fistula (esophagus / bronchus or esophagus / aorta);
• Patients with severe malnutrition, with body mass index lower than 18.5kg/m2, or PG-SGA score ≥9；
• Any active autoimmune disease or history of autoimmune disease (as follows, but not limited to: interstitial pneumonia, uveitis, enteritis, autoimmune hepatitis, pituitritis, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction); Subjects with vitiligo or who have had complete remission from childhood asthma without any intervention after adulthood may be included; Asthma requiring medical intervention with bronchodilators was not included.
• Has a previous radiotherapy, chemotherapy, hormone therapy, surgery, molecular targeted therapy or immune therapy for this malignancy or for any other past malignancy;
• Any condition requiring systemic corticosteroid therapy (prednisone with a dose higher than 10 mg / day or equivalent dose of similar drugs) or other immunosuppressants within 14 days before treatment. （Excluding the following steroid regimens：Local, ophthalmic, intra-articular, nasal and inhaled corticosteroids with minimal systemic absorption；Prophylactic short-term (≤ 7 days) use of corticosteroids (e.g., prevention of contrast media allergy) or for the treatment of non-autoimmune disorders (e.g., delayed hypersensitivity caused by exposure to allergens).
• Live vaccine injection was received in ≤ 4 weeks before treatment.
• A history of immunodeficiency, including HIV infection, other acquired or congenital immunodeficiency, or a history of organ or bone marrow implantation that need immunosuppressive medications.
• There are clinical symptoms or diseases of the heart that are not well controlled, such as: 1). heart failure above grade 2 by the Criteria of NYHA; 2). unstable angina pectoris; 3). myocardial infarction occurred within 1 year; 4). Clinically meaningful supraventricular or ventricular arrhythmias require treatment or intervention;
• Has severe infections （CTCAE\>2 grade）within 4 weeks before treatment; basal thoracic imaging indicating active pneumonia, or other infectious situation that need oral or intravenous antibiotic treatment (excluding Prophylactic medication for antibiotics).
• A history of interstitial lung disease, non-infectious pneumonia or uncontrolled disease, including pulmonary fibrosis, acute lung disease, etc.
• Allergic to any drug used in this study.
• Pregnant or lactating women；participants who unwilling to take contraception.
• Other factors that could lead to the termination of this study.

Sponsors & Collaborators

• Jiangsu Cancer Institute & Hospital: lead

Study Sites (1)

Jiangsu Cancer Hospital /Jiangsu Institute of Cancer Research

Nanjing, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Neoadjuvant 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)

Combined Modality Therapy; Therapeutics

Study Officials

• Xiangzhi Zhu, M.D.

  Jiangsu Cancer Institute & Hospital

  STUDY DIRECTOR

• Ming Jiang, M.D.

  Jiangsu Cancer Institute & Hospital

  STUDY DIRECTOR

• Feng Jiang, M.D.

  Jiangsu Cancer Institute & Hospital

  STUDY DIRECTOR

Central Study Contacts

Xiangzhi Zhu, M.D.

CONTACT

+86 25 83283535; 13182948068@163.com

Ning Jiang, M.D.

CONTACT

+86 25 83283535; njiang117@njmu.edu.cn

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: M.D.

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: June 21, 2022
• Study Start: April 29, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: June 27, 2022

Record last verified: 2022-06

Locations

CN (1)