Neoadjuvant therapy with immunotherapy for esophageal cancer

Watch and Wait for NeoAdjuvant Concurrent Radiochemotherapy Combined With Camrelizumab in Patients With Resectable Esophageal Squamous Cell Carcinoma，A Prospective, Single-Center, Open Label，Phase II Cohort Study （WATCHER）

This study is testing a new treatment combining radiation, chemotherapy, and an immunotherapy drug to see if it helps people with esophageal cancer before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, camrelizumab
• Locations: 3 sites (Hanzhou, Zhejiang and 2 other locations)
• Trial ID: NCT05507411 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of a neoadjuvant treatment approach combining concurrent radiochemotherapy and the immunotherapy drug camrelizumab in patients with resectable esophageal squamous cell carcinoma. Eligible participants will receive a specific dosage of radiotherapy and chemotherapy, followed by evaluations to determine if they achieve clinical complete resection. Those who do will be randomly assigned to either undergo surgery or be monitored through a watchful waiting strategy. The study aims to assess the 1-year disease-free survival rate among participants.

Who should consider this trial

Good fit: Ideal candidates are patients with thoracic esophageal squamous cell carcinoma at clinical stages cT2-4aNanyM0 or cT1-3N+M0.

Not a fit: Patients with major associated pathological conditions that increase surgical risks or those with non-resectable esophageal cancer will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve disease-free survival rates and reduce the need for immediate surgery in patients with esophageal cancer.

How similar studies have performed: Other studies have shown promise with similar neoadjuvant therapies, but this specific combination of treatments is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Sign the informed consent. Participants signed and dated written informed consent. Informed consent must be signed prior to any protocol-related procedures that are not part of the participant's routine medical care； Participants must be willing and able to comply with scheduled visits, treatment regimens, and laboratory tests；
2. Participant type and target disease characteristics Eastern Collaboration Group (ECOG) physical status score 0-1； Histologically confirmed esophageal cancer with lesions located in the thoracic esophagus, AJCC/UICC esophageal cancer staging (eighth edition) clinical stage cT2-4aNanyM0, or cT1-3N+M0； Presence of measurable lesions according to RECIST criteria； Participants must have tumor tissue samples available for PD-L1 IHC testing； No major associated pathological conditions that increase the risk of surgery to unacceptable levels. Such as: esophageal perforation and active esophageal bleeding, obvious trachea, thoracic large blood vessel invasion； According to the surgeon's assessment, the total lung function can withstand the proposed esophageal cancer resection；
3. Age and reproductive status Age ≥18 years old and ≤75 years old； Females of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity of 25 IU/L or equivalent for HCG) within 24 hours prior to initiation of study treatment； Women must be non-nursing；

Exclusion Criteria:

1\) Medical condition There is locally advanced unresectable (regardless of stage) or metastatic disease.

Participants with Grade ≥2 Peripheral Neuropathy； Participants with active, known or suspected autoimmune disease. Participants with type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, skin disorders that do not require systemic treatment (eg, vitiligo, psoriasis, or alopecia), or disorders that are not expected to recur in the absence of external stimuli are eligible to be enrolled； Participants requiring systemic therapy with glucocorticoids (\>10 mg prednisone equivalent daily) or other immuno suppressive drugs within 14 days prior to treatment. In the absence of active autoimmune disease, inhaled or topical steroids and adrenal hormone replacement therapy at \>10 mg prednisone-equivalent daily are permitted； Known history of positive human immuno deficiency virus (HIV) test or known acquired immuno deficiency syndrome (AIDS)； Participants with serious or uncontrolled medical illness； previous/concomitant therapy； Received chest radiotherapy, chemotherapy, immunotherapy, or surgery of the esophagus, esophagus and gastric junction, or stomach prior to the start of the trial.

Patients with severe cardiovascular or pulmonary disease, interstitial pneumonia, or previous history of interstitial pneumonia； Patients with obvious esophageal ulcers, moderate pain in the chest and back, and esophageal perforation symptoms； Physical examination and laboratory test results

Laboratory screening values must meet the following criteria (using CTCAE 4th edition):

i) WBC \< 2000/μL； ii) Neutrophils \< 1500/μL； iii) Platelets \< 100x103/μL； iv) Hemoglobin \< 9.0 g/dL； v) Serum creatinine \<1.5 x ULN or calculated creatinine clearance (CrCl) \< 50 mL/min (using Cockcroft-Gault formula)； vi) AST \>3.0 x ULN； vii) ALT \> 3.0 x ULN； viii) Total bilirubin \>1.5 x ULN (except for Gilbert syndrome participants, who had total bilirubin \< 3.0 x ULN)； Participants had active hepatitis B (positive for hepatitis B surface antigen \[HBsAg\] or positive for hepatitis C virus (HCV) (positive for HCV RNA)； i) Participants with previous or recovered HBV infection (defined as having hepatitis B core antibody \[HBcAb\] and no HBsAg) are eligible. HBV DNA from these patients must be obtained prior to treatment. Participants who are HBV carriers or require antiviral therapy are not eligible； ii) Participants positive for HCV antibodies are eligible only if PCR for HCV RNA is negative.； Active malignancy within the past 3 years, except for locally curable cancers that have been significantly cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast； Participants with serious or uncontrolled medical conditions； Allergic Reactions and Adverse Drug Reactions； History of allergic reactions or hypersensitivity reactions to study drug components Other exclusion criteria； Patients who do not understand trial requirements, or who may not comply with trial requirements； Active infection requiring systemic therapy 14 days prior to first dose Some obvious diseases that the researchers believe should be excluded from this study；

Where this trial is running

Hanzhou, Zhejiang and 2 other locations

• The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU) — Hanzhou, Zhejiang, China (Not_yet_recruiting)
• Zhejiang Cancer Hospital — Hanzhou, Zhejiang, China (Recruiting)
• Ningbo Medical Center Lihuili Hospital — Ningbo, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Qixun Chen — Zhejiang Cancer Hospital
• Study coordinator: Qixun Chen

Conditions Esophageal Squamous Cell Carcinoma; NeoAdjuvant therapy; immunotherapy; Concurrent Radiochemotherapy; organ preservation