Complete Cytoreduction Followed by IP and Systemic Chemotherapies for Gastric Cancer With Peritoneal Carcinomatosis

NCT04547725 | Recruiting DMC

• 1 other identifier: 202006125RINC
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Approximately 15% of gastric adenocarcinoma patients presents with peritoneal carcinomatosis (PC) at the first encounter and is regarded as an unresectable and end-stage disease. The recommended treatment with palliative chemotherapy alone yields a poor clinical efficacy. Emerging evidences suggest the survival benefits of complete cytoreductive surgery (CRS) combined with normothermic intraperitoneal chemotherapy (N-IPEC) for gastric adenocarcinoma with limited PC. Objective: To evaluate the 6-month disease control rate (DCR) of complete CRS combined with N-IPEC and systemic chemotherapy for gastric adenocarcinoma with limited PC. Patients and methods: Patients having gastric adenocarcinoma with PCI ≤ 10 (Arm-A) or positive peritoneal wash cytology (CY1/P0) (Arm-B) will be enrolled. Patients with other distant metastasis, including brain, lung, liver, bone, will be excluded. All patients should undergo ≥ D2 gastrectomy and complete CRS followed by N-IPEC (paclitaxel\] and systemic chemotherapy (high-dose fluorouracil and cisplatin \[P-HDFL\], or capecitabine and oxaliplatin \[CAPOX\]). N-IPEC (paclitaxel) will be administered in combination with systemic P-HDFL or CAPOX on day 1,8,15 or day 1,8 for each cycle, respectively. The disease status will be evaluated every 12 weeks based on the computed tomography scan, and the clinical evaluation (outpatient follow-up) will be performed every 2 weeks for whom receiving P-HDFL and every 3 weeks for whom receiving CAPOX. Patients will receive maximal 6 cycles N-IPEC with P-HDFL or 8 cycles N-IPEC with CAPOX. After N-IPEC is discontinued, P-HDFL or CAPOX will be continued alone until disease progression or death. The primary endpoint of this study is 6-month DCR, and the secondary endpoints include 6-month response rate for ascites, 1-year progression-free survival (PFS) and overall survival (OS), 3-year PFS and OS, and safety profiles. Based on Simon's minimax two-stage design, this trial will be carried out in two stages. In stage I, a total number of 13 (Arm-A) / 16 (Arm-B) patients is accrued. If there are ≤ 6 (Arm-A) / ≤ 14 (Arm-B) progression-free among these 13 (Arm-A) / 16 (Arm-B) patients, the study will be early stopped. Otherwise, additional 17 (Arm-A) / 2 (Arm-B) patients will be accrued in stage II, resulting in a total number sample size of 30 (Arm-A) / 18 (Arm-B). Expected result: A ≥ 75% (Arm-A) / ≥ 95% (Arm-B) 6-month DCR could be achieved for gastric adenocarcinoma patients with limited PC (Arm-A) / with CY1P0 (Arm-B) via this treatment strategy (complete CRS + N-IPEC + P-HDFL or CAPOX) -i.e., if there are ≥ 21 (Arm-A) / ≥ 16 (Arm-B) progression-free among the 30 (Arm-A) / 18 (Arm-B) enrolled patients, we will reject the null hypothesis and claim that the treatment is promising.

Conditions

Gastric Cancer; Peritoneal Carcinomatosis

Keywords

gastric cancer; peritoneal carcinomatosis; cytoreductive surgery; intraperitoneal chemotherapy

Outcome Measures

Primary Outcomes (1)

• 6-month disease control rate

  The 6-month disease control rate is defined as the percentage of patients with no occurrence of radiological PD (per RECIST 1.1), clinical PD (based on investigator's judgement), or death from any cause, after 24 weeks (\~ 6 months) from the beginning of combined IP and systemic chemotherapies.

  6 months

Secondary Outcomes (4)

• Progression-free survival (PFS)

  3 years

• Overall survival (OS)

  3 years

• 6-month response rate for ascites.

  6 months

• Safety evaluation

  9 months

Study Arms (2)

CRS-IP (Arm-A)

EXPERIMENTAL

Stage IV gastric cancer with limited peritoneal carcinomatosis (peritoneal carcinomatosis index \[PCI\] ≤ 10)

Other: CRS followed by IP and systemic chemotherapies

CRS-IP (Arm-B)

EXPERIMENTAL

Stage IV gastric cancer with positive peritoneal wash cytology (CY1/P0)

Other: CRS followed by IP and systemic chemotherapies

Interventions

CRS followed by IP and systemic chemotherapies OTHER

Complete cytoreductive surgery (CRS) + normothermic intraperitoneal chemotherapy (N-IPEC) + systemic chemotherapy

CRS-IP (Arm-A); CRS-IP (Arm-B)

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 20 to 75 years old.
• Blood tests:
• White blood cells \> 4,000/mm3, neutrophils \> 1,500/mm3, platelets \> 100,000/mm3.
• Serum creatinine \< 1.5 mg/dl or creatinine clearance \> 60 ml/min.
• Serum bilirubin \< 2 mg/dl.
• Eastern Cooperative Oncology Group (ECOG) Performance Status = 0 or 1.
• Not legal incapacity.
• Newly diagnosed gastric adenocarcinoma, including Siewert III adenocarcinoma of the cardia, with limited peritoneal carcinomatosis (PCI ≤ 10) or positive peritoneal wash cytology (CY1/P0) .

You may not qualify if:

• Prior malignancy within 3 years or with detectable signs of recurrence.
• Newly diagnosed gastric adenocarcinoma having been treated by preoperative systemic or intraperitoneal chemotherapy.
• Presence of comorbidities, including liver cirrhosis (≥ Child B), decompensated heart failure (New York Heart Association \[NYHA\] Class III or IV congestive heart failure), poorly-controlled chronic obstructive pulmonary disease.
• ≥ American Society of Anesthesiologists Classification (ASA Class) Class 3.
• Pregnancy or breastfeeding.
• Intolerability of chemotherapeutic agents in this study:
• N-IPEC paclitaxel (all patients).
• Capecitabine or oxaliplatin (patients who receive CAPOX regimen).
• Cisplatin or 5-fluorouracil (patients who receive P-HDFL regimen).
• Distant metastases (e.g. liver, lung, bone) except for the peritoneum, intra-abdominal lymph node, and ovary.
• Extensive PC (PCI \> 10).
• Siewert I or II adenocarcinoma of the cardia.
• Other patients inappropriate for this study in the opinion of the investigators.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Peritoneal Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• I-Rue Lai, MDPHD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hung-Hsuan Yen, MD

CONTACT

0910012718; yhhdean@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Arm-A: resectable advanced gastric adenocarcinoma with limited PC (PCI ≤ 10) Arm-B: resectable advanced gastric adenocarcinoma with positive peritoneal wash cytology (CY1/P0)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Complete cytoreductive surgery followed by intraperitoneal and systemic chemotherapies

Study Record Dates

• First Submitted: September 2, 2020
• First Posted: September 14, 2020
• Study Start: September 16, 2020
• Primary Completion: March 16, 2026
• Study Completion (Estimated): September 16, 2028
• Last Updated: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)