Clinical trial NCT04515615: Adjuvant Chemotherapy in Combination With Camrelizumab for Stage III Gastric Cancer (FOCUS-02)
Official title: A Multi-center, Phase II Study to Evaluate Safety and Efficacy of Adjuvant Chemotherapy With Tegafur Gimeracil Oteracil Potassium Capsule Plus Oxaliplatin and Camrelizumab for Stage III Gastric Cancer (FOCUS-02)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer Stage III
Keywords: Gastric cancer
Camrelizumab
Chemotherapy
Phase II
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
First posted: 2020-08-17
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a prospective, single arm, multi-center phase II clinical trial. The primary study objective is to evaluate the safety of tegafur gimeracil oteracil potassium capsule plus oxaliplatin and Camrelizumab as adjuvant therapy in stage III gastric cancer, including the incidences and types of adverse events. The secondary study objective is to observe and evaluate the disease-free survival (DFS), overall survival (OS) and treatment completion rate.

Detailed description: 1. Study population: participants with stage III gastric cancer confirmed by postoperative pathology according to American Joint Committee on Cancer (AJCC) / Union for International Cancer Control (UICC) 8th Tumor Node Metastasis (TNM) staging classification.
2. Sample size: single arm design was used in this study and 52 participants were estimated to be enrolled.
3. Research content: In this study, within 4-6 weeks after the completion of the operation, the participants were selected and qualified for this study, and were scheduled to receive 200mg camrelizumab once intravenous infusion on the first day (q3w), then 130mg/m\^2 oxaliplatin on the first day (q3w), and tegafur gimeracil oteracil potassium capsule was taken as follow: surface area is less than 1.25, 80mg per day, twice a day; ≥1.25 \~ \<1.5, 100mg per day, twice a day; ≥1.5, 120mg per day, twice a day, and oral administration for 1-14 days every 3 weeks. Three weeks as a course of treatment, a total of 8 courses, after treatment, safety visit and survival follow-up will be carried out. A total of 3 years follow-up time is scheduled since the first medication, and the frequency is once every 3-6 months within 2 years, and once every 6-12 months for the third year.
4. Adverse events (AEs) management: To minimize the risk of AEs, the investigators will monitor carefully to determine whether or not they are within the expected range. The degree of AEs is evaluated according to The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.0). Investigators will also conduct a thorough examination and adopt an appropriate system to take any necessary measures to deal with AEs.

Eligibility criteria: Inclusion Criteria:

1. Voluntary participation in the clinical study; fully understands and is informed of the study and has signed the Informed Consent Form (ICF).
2. The gender is not limited. Age: ≥ 18 years and ≤ 75 years old.
3. Gastric or gastroesophageal junction adenocarcinoma confirmed by pathology.
4. Without evidence of distant metastatic disease before operation by imaging.
5. Received D2 or D2+ radical gastrectomy by open surgery (R0 resection).
6. Stage III gastric cancer confirmed by postoperative pathology (AJCC/UICC 8th TNM staging classification).
7. Participants with a performance status of 0 \~ 1 on the Eastern Cooperative Oncology Group (ECOG) within 7 days before the first dose of study treatment.
8. Life expectancy ≥ 6 months.
9. The functions of the vital organs meet requirements as follow (within 14 days before the first dose of study treatment, participant has not received treatment of blood transfusion, albumin, recombinant human thrombopoietin or granulocyte stimulating factor):

   A. Hematological function：
   * White blood cell count (WBC): 3.5 × 10 \^ 9 / L \~12.0 × 10 \^ 9 / L；
   * Absolute neutrophil count (ANC) ≥ 1.5 × 10 \^ 9 / L；
   * Platelet count (PLT) ≥ 100 × 10 \^ 9 / L；
   * Hemoglobin (Hb) ≥ 90 g / L.

   B. Hepatic function：
   * Total bilirubin (TBIL) ≤ 1.5 × ULN (upper limit of normal);
   * Aspartate aminotransferase (AST) ≤ 2.5 × ULN;
   * Alanine aminotransferase (ALT) ≤ 2.5 × ULN;
   * Albumin (ALB) ≥ 30 g / L.

   C. Renal function：
   * Creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 60 ml / min for those with creatinine level \> 1.5 × ULN.

   D. Coagulation function：
   * International normalized ratio (INR) ≤ 1.5;
   * Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
10. Female of childbearing age must meet requirements: urine pregnancy test must be negative within 7 days before the first dose of study treatment, and she must agree to use adequate contraception methods or keep abstinence (starting with the ICF is signed through 120 days after the last dose of camrelizumab, or 180 days after the last dose of chemotherapy, whichever is longer, and should not be breastfeeding. For the male participants must meet requirements: agree to use adequate contraception methods or keep abstinence (starting with the ICF is signed through 120 days after the last dose of camrelizumab, or 180 days after the last dose of chemotherapy, whichever is longer).

Exclusion Criteria:

1. Received previous chemotherapy, radiotherapy, targeted therapy or immunotherapy.
2. Previous or concurrent have other active malignant tumors (except for basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate cancer or cervical cancer or breast cancer in situ that has undergone curative therapy).
3. Existence of unrecovered complications after radical gastrectomy before the first dose of study treatment (including but not limited to: infection, gastrointestinal bleeding/ obstruction, anastomotic fistula, pancreatic fistula and anastomotic stenosis).
4. Myocardial infarction within 6 months before the first dose of study treatment, uncontrolled angina, arrhythmia which need medical intervention (including but not limited to cardiac pacemaker), congestive heart failure (New York Heart Association (NYHA) class III or IV), echocardiogram shows left ventricular ejection fraction (LVEF) \< 50%.
5. Existence of chronic diarrhea (watery diarrhea: ≥ 5 times per day).
6. Participants with active infection within 14 days before the first dose of study treatment which need medical intervention.
7. Participants with active tuberculosis.
8. Previous or concurrent diagnosed with interstitial lung disease by imaging or symptoms.
9. Any of the following test is positive: Human Immunodeficiency Virus (HIV) antibody, Hepatitis B surface Antigen (HBsAg), or Hepatitis C Virus (HCV) antibody.
10. Females who are pregnant or breastfeeding or expecting to conceive during the study period.
11. Participants who need long-term systemic steroid therapy (\> 10 mg/d prednisone equivalent) or any other form of immunosuppressive therapy within 14 days before the first dose of study treatment or during the study period.
12. Concurrent or previous have severe allergic reaction to any antibody-based drugs.
13. Existence of any concurrent autoimmune disease, excepting participants with diabetes mellitus type I, hypothyroidism requiring only hormone replacement therapy and skin diseases without systemic treatment (such as vitiligo, psoriasis or alopecia).
14. Receive live vaccines within 28 days before the first dose of study treatment or during the study period, excepting inactivated viral vaccines for seasonal influenza.
15. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
16. Existence of systemic disease that is difficult to control despite treatment with several agents, for example, diabetes mellitus, hypertension, etc.
17. Existence of other serious physical or mental diseases or serious laboratory abnormalities that may increase the risk of participating in the study. Participants who were judged unsuitable as subjects of this trial by investigator.

Primary outcomes:
measure: The incidences and types of adverse events
timeFrame: 9 months
Secondary outcomes:
measure: Disease-free survival (DFS)
timeFrame: 3 years
measure: Overall survival (OS)
timeFrame: 3 years
measure: Treatment completion rate
timeFrame: 6 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
city: Lishui
country: China
facility: Lishui Central Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The Second Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Zhejiang University
name: Jiren Yu
role: PRINCIPAL_INVESTIGATOR
References: