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

• ClinicalTrials.gov Identifier: NCT03061058
• Recruitment Status: Unknown
• First Posted: February 23, 2017
• Last Update Posted: September 15, 2017
• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Information provided by (Responsible Party): Yang Yang, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Tracking Information

• First Submitted Date: February 11, 2017
• First Posted Date: February 23, 2017
• Last Update Posted Date: September 15, 2017
• Actual Study Start Date: April 1, 2013
• Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2017)

Progression-free Survival (PFS) [ Time Frame: up to 1 year ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 17, 2017)

• Overall Survival (OS) [ Time Frame: up to 2 years ]
  OS means that from the first dose of treatment drug to death or lost, the follow-up visit will be performed every 3 months till death or lost
• Objective Response Rate [ Time Frame: up to 24 weeks ]
  CT/MRI will be performed every 2 cycles of treatment for efficacy evaluation
• Adverse Events [ Time Frame: up to 1 months ]
  participants will be followed for the duration of hospital stay

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment

Condition

• Stomach Neoplasms
• Chemotherapy Effect
• Chemotherapeutic Toxicity

Intervention

• Drug: Docetaxel
  intraperitoneal and/or intravenous
• Drug: Oxaliplatin
  intravenous
• Drug: Cisplatin
  intraperitoneal
• Drug: Irinotecan
  intraperitoneal and/or intravenous
• Drug: Pemetrexed
  intraperitoneal and/or intravenous
• Drug: S1
  oral

Study Arms

• Experimental: Individualized Group

  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).

  Interventions:

  • Drug: Docetaxel
  • Drug: Oxaliplatin
  • Drug: Cisplatin
  • Drug: Irinotecan
  • Drug: Pemetrexed
  • Drug: S1
• Active Comparator: Control Group

  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).

  Interventions:

  • Drug: Docetaxel
  • Drug: S1

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: September 13, 2017): 240
• Original Estimated Enrollment (submitted: February 17, 2017): 120
• Estimated Study Completion Date: December 2019
• Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03061058
• Other Study ID Numbers: AGC-PC
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Yang Yang, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Study Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Verification Date: September 2017