Neoadjuvant Toripalimab for dMMR/MSI-H Gastric Cancer

NCT05994456 | Unknown Phase 2

• 1 other identifier: HP001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open phase II clinical trial to evaluate the tolerability, safety and efficacy of toriparib monotherapy in the treatment of locally advanced dMMR/MSI-H gastric or gastroesophageal junction adenocarcinoma.

Conditions

Gastric or Gastroesophageal Junction Adenocarcinoma

Keywords

dMMR/MSI-H; Gastric cancer

Outcome Measures

Primary Outcomes (1)

• Pathological complete remission (pCR) rates

  Percentage of patients who achieve pathological complete remission (pCR)

  12 weeks

Secondary Outcomes (4)

• R0 resection rates

  12 weeks

• three-year disease-free survival rate, DFS

  3 years

• three-year Overall survival rate,OS

  3 years

• Incidence of Treatment-Related Adverse Events

  3 years

Study Arms (1)

PD-1 inhibitor

EXPERIMENTAL

Neoadjuvant therapy with PD-1 inhibitor (Toripalimab)

Drug: PD-1 inhibitor

Interventions

PD-1 inhibitor DRUG

240mg, Q3W. The opportunity for surgery was evaluated after 2 cycles of treatment and surgical treatment was performed after 2-4 cycles of treatment. Postoperatively, adjuvant therapy was continued according to the neoadjuvant regimen, and direct treatment met the criteria for termination of treatment.

Also known as: Toripalimab

PD-1 inhibitor

Eligibility Criteria

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

You may qualify if:

• \. Aged 18-75 years, regardless of gender 2. Patients with histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction and confirmed dMMR or MSI-H 3. Preoperative CT or MRI staging meeting the following criteria: T2 and above, with or without lymph node involvement, without clear distant metastasis 4. ECOG score of 0-1. 5. Expected survival ≥ 2 years. 6. Good organ function (no blood transfusion, no hematopoietic stimulating factor, no albumin or blood product transfusion within 14 days prior to the examination).
• Platelet (PLT) count ≥ 90\*109/L.
• Neutrophil count (ANC) ≥ 1.5\*109/L.
• Hemoglobin (Hb) level ≥ 9.0 g/dl.
• International normalized ratio (INR) ≤ 1.5.
• Prothrombin time (PT) and active partial thromboplastin time (APTT) ≤ 1.5 x ULN.
• Glycated hemoglobin (HbA1c) \<7.5%.
• Total bilirubin (TBIL) level ≤ 1.5 times the upper limit of normal (ULN).
• Alanine amino transaminase (ALT) and aspartate amino transaminase (AST) levels ≤ 2.5 x ULN.
• Serum creatinine (Cr) level ≤ 1.5 x ULN and creatinine clearance ≥ 60 ml/min.
• Thyrotropin (TSH) ≤ ULN; serum free thyroid hormone (T4) normal; serum free triiodothyronine (T3) normal; (except for those who have received previous thyroid surgery or have a history of head and neck radiotherapy)
• Serum amylase ≤ 1.5 x ULN.
• Lipase ≤ 1.5×ULN. 7. Women of childbearing age must have a negative pregnancy test and must use contraception and avoid breastfeeding during the study and for 3 months after the last dose; male subjects must agree to use contraception during the study and for 3 months after the last dose.
• Be able to understand and willing to sign a written informed consent form.

You may not qualify if:

• Previously received chemotherapy, radiotherapy or immunotherapy for gastric cancer
• Previously diagnosed any other malignancy with a primary site or histological type different from gastric cancer within 5 years prior to study entry, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• With known hypersensitivity to the study drug or excipients, or to similar drugs
• Received major surgery or open biopsy, or had a major trauma within 4 weeks prior to the start of study treatment
• Received immunosuppressive drugs (excluding inhaled corticosteroids or ≤10 mg/day prednisone or equivalent pharmacophysiologic doses of other systemic steroids) within 2 weeks prior to the start of study treatment
• Planned live attenuated vaccination within 4 weeks prior to the start of study treatment or during the study period
• Inability to discontinue CYP3A4 inducers or inhibitors within 1 week prior to the start of study treatment and during the study period
• Presence of any autoimmune disease or history of autoimmune disease.
• Human immunodeficiency virus (HIV) infection (HIV antibody positive), or active hepatitis C virus (HCV) infection (HCV antibody positive), or active hepatitis B virus (HBV) infection (HBsAg positive and HBV-DNA ≥ 2000 IU/ml copies/ml)), or other serious infection requiring antibiotics for systemic therapy, or during screening/study Unexplained temperature \>38.5°C prior to the start of treatment.
• Presence of the following diseases within 6 months prior to the start of study treatment: myocardial infarction, severe/unstable angina, NYHA class 2 or higher congestive heart failure, poorly controlled arrhythmias, etc.
• Non-well-controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg under optimal treatment)
• Arterial/venous thrombotic events such as cerebrovascular accidents (transient ischemic attack, cerebral hemorrhage, cerebral infarction, etc.), deep vein thrombosis, vasculitis, etc. within 3 months prior to the start of study treatment
• Urine routine suggesting urine protein up to +++ and confirmed 24-hour urine protein quantification up to 1.0g.
• The presence of a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
• Seizures requiring medication (e.g., steroids or antiepileptic drugs) for treatment.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Immune Checkpoint Inhibitors; toripalimab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Dongsheng Zhang, PhD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dongsheng Zhang, PhD

CONTACT

86-2087343795; zhangdsh@sysucc.org.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: Professor

Study Record Dates

• First Submitted: August 9, 2023
• First Posted: August 16, 2023
• Study Start: March 9, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: August 16, 2023

Record last verified: 2023-08

Locations

CN (1)