Clinical trial NCT03061058: Individualized Intraperitoneal and System Chemotherapy Versus System Chemotherapy as First-line Chemotherapy for AGC
Official title: An Open-label, Randomized, Phase III, Multicenter Clinical Trial Comparing the Efficacy and Safety of Individualized Intraperitoneal and System Chemotherapy Versus System Chemotherapy as First-line Chemotherapy for Advanced Gastric Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Stomach Neoplasms
Chemotherapy Effect
Chemotherapeutic Toxicity
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2017-02-23
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Tumor messenger ribonucleic acid (mRNA) expression levels may have a promising role as potential predictive biomarkers for chemotherapy.

Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Intraperitoneal chemotherapy is widely accepted strategy in the treatment of peritoneal dissemination.

In this study, our aim is to evaluate the impact of individualized selection of chemotherapeutics and intraperitoneal combined with system chemotherapy on overall survival, disease free survival, response rate, and safety of advanced gastric cancer patients.


Eligibility criteria: Inclusion Criteria:

* Patients must have histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable locally advanced or metastatic disease, not amenable to curative therapy.
* Patients must have measurable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1), assessed using imaging techniques (CT or MRI).
* Patients must have enough tumor tissue for mRNA expression test.
* Women of childbearing potential must be non-pregnant (negative pregnancy test within 72 hours prior to chemotherapy, postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential) and nonlactating, and men and women must be willing to exercise an effective form of birth control (abstinence/contraception) while on study and for 6 months after therapy completed
* Eastern Cooperative Oncology Group (ECOG) Performance status 0, 1 or 2.
* Absolute neutrophil count (ANC) \>=1,500/ul
* Platelets (PLT) \>=75,000/ul
* Serum bilirubin \<= 1.5 × upper limit of normal (ULN)
* Aspartate transaminase (AST) or alanine aminotransferase (ALT) \<= 2.5 × ULN (or \<= 5 × ULN in patients with liver metastases)
* Alkaline phosphatase \<= 2.5 × ULN (or \<= 5 × ULN in patients with liver metastases, or \<= 10 × ULN in patients with bone but no liver metastases)
* Albumin \>= 25 g/L.
* Creatinine clearance \>= 60 mL/min.
* Life expectancy of at least 3 months.
* Signed informed consent.

Exclusion Criteria:

* Previous chemotherapy for advanced/metastatic disease (prior adjuvant/neoadjuvant therapy is allowed if at least 6 months has elapsed between completion of adjuvant/neoadjuvant therapy and enrolment into the study; the total dose of cisplatin should be less than 300mg/m\^2).
* Patients with active (significant or uncontrolled) gastrointestinal bleeding.
* Residual relevant toxicity resulting from previous therapy (with the exception of alopecia), e.g. neurological toxicity ≥ grade 2 NCI-CTCAE 4.0.
* Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma.
* History of documented congestive heart failure; angina pectoris requiring medication;evidence of transmural myocardial infarction on ECG; poorly controlled hypertension (systolic BP \> 180 mmHg or diastolic BP \> 100 mmHg); clinically significant valvular heart disease; or high risk uncontrollable arrhythmias.
* Baseline left ventricular ejection fraction (LVEF) \< 50% (measured by echocardiography or MUGA).
* Patients with dyspnoea at rest due to complications of advanced malignancy or other disease, or who require supportive oxygen therapy.
* Patients receiving chronic or high dose corticosteroid therapy. (Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed).
* Clinically significant hearing abnormality.
* Known dihydropyrimidine dehydrogenase (DPD) deficiency.
* History or clinical evidence of brain metastases.
* Serious uncontrolled systemic intercurrent illness, e.g. infections or poorly controlled diabetes.
* Positive serum pregnancy test in women of childbearing potential.
* Received any investigational drug treatment within 4 weeks of start of study treatment.
* Radiotherapy within 4 weeks of start of study treatment (2 week interval allowed if palliative radiotherapy given to bone metastatic site peripherally and patient recovered from any acute toxicity;prior adjuvant radiotherapy is allowed if complete at least 6 months ).
* Major surgery within 4 weeks of start of study treatment, without complete recovery.
* Patients with known active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV).
* Known hypersensitivity to any of the study drugs.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: up to 1 year
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: up to 2 years
measure: Objective Response Rate
timeFrame: up to 24 weeks
measure: Adverse Events
timeFrame: up to 1 months
Other outcomes:
Locations:
city: Ma'anshan
country: China
facility: Ma'anshan People's Hospital
state: Anhui
city: Jiangyin
country: China
facility: Jiangyin People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Gaochun People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Lishui People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The Comprehensive Cancer Center of Nanjing Drum Tower Hospital
state: Jiangsu
city: Suqian
country: China
facility: Suqian People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Zhenjiang
country: China
facility: Affiliated Hospital of Jiangsu University
state: Jiangsu
Study officials:
References: