Individualized Intraperitoneal and System Chemotherapy Versus System Chemotherapy as First-line Chemotherapy for AGC

NCT03061058 | Unknown Phase 3

• 1 other identifier: AGC-PC
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 8

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.

Conditions

Stomach Neoplasms; Chemotherapy Effect; Chemotherapeutic Toxicity

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  the follow-up visit of PFS will be performed every 6 weeks

  up to 1 year

Secondary Outcomes (3)

• Overall Survival (OS)

  up to 2 years

• Objective Response Rate

  up to 24 weeks

• Adverse Events

  up to 1 months

Study Arms (2)

Individualized Group

EXPERIMENTAL

mRNA levels of BRCA1, topoisomerase I (TOPO1), and thymidylate synthase (TS) were assessed in tumor tissue. Chemotherapeutic agents were selected based on the mRNA levels. Patients with high level BRCA1 will receive intraperitoneal docetaxel (15mg/m\^2, d1, d15, q4w), intravenous docetaxel (30mg/m\^2, d1, d15, q4w), and oral S-1 (40mg/m\^2, d1-14, q4w). Patients with low level BRCA1 will receive intraperitoneal cisplatin (25mg/m\^2, d1, d15, q4w), intravenous oxaliplatin (75mg/m\^2, d1, d15, q4w), and oral S-1 (40mg/m\^2, d1-14, q4w). Patients with middle level BRCA1 and high level TOPO1 will receive intraperitoneal irinotecan (45mg/m\^2, d1, d15, q4w), intravenous docetaxel (90mg/m\^2, d1, d15, q4w), and oral S-1 (40mg/m\^2, d1-14, q4w). Patients with middle level BRCA1, low or middle level TOPO1, and low level TS will receive intraperitoneal pemetrexed (150mg/m\^2, d1, q3w), and intravenous pemetrexed (350mg/m\^2, d1, q3w).

Drug: Docetaxel; Drug: Oxaliplatin; Drug: Cisplatin; Drug: Irinotecan; Drug: Pemetrexed; Drug: S1

Control Group

ACTIVE COMPARATOR

mRNA levels of BRCA1, TOPO1, and TS were assessed in tumor tissue for every enrolled patients. Patients in control group will receive intravenous docetaxel (45mg/m\^2, d1, d15, q4w), and oral S-1 (40mg/m\^2, d1-14, q4w).

Drug: Docetaxel; Drug: S1

Interventions

Docetaxel DRUG

intraperitoneal and/or intravenous

Control Group; Individualized Group

Oxaliplatin DRUG

intravenous

Individualized Group

Cisplatin DRUG

intraperitoneal

Individualized Group

Irinotecan DRUG

intraperitoneal and/or intravenous

Individualized Group

Pemetrexed DRUG

intraperitoneal and/or intravenous

Individualized Group

S1 DRUG

oral

Control Group; Individualized Group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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 ).

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Study Sites (8)

Ma'anshan People's Hospital

Ma’anshan, Anhui, China

RECRUITING

Jiangyin People's Hospital

Jiangyin, Jiangsu, China

RECRUITING

Nanjing Gaochun People's Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Nanjing Lishui People's Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

The Comprehensive Cancer Center of Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

RECRUITING

Suqian People's Hospital

Suqian, Jiangsu, China

RECRUITING

Xuzhou Central Hospital

Xuzhou, Jiangsu, China

RECRUITING

Affiliated Hospital of Jiangsu University

Zhenjiang, Jiangsu, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Docetaxel; Oxaliplatin; Cisplatin; Irinotecan; Pemetrexed; S 1 (combination)

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Camptothecin; Alkaloids; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Central Study Contacts

Yang Yang, MD,PhD,MSCR

CONTACT

0086-18602568379; wing_young7@hotmail.com

Baorui Liu, MD, PhD

CONTACT

0086-13770621908; baoruiliu07@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: February 11, 2017
• First Posted: February 23, 2017
• Study Start: April 1, 2013
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: September 15, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (8)