A Phase Ib/II Study of Efficacy and Feasibility of Cytoreductive Surgery, Extensive Peritoneal Lavage, Hyperthermicintraperitoneal Chemotherapy and Post-operative Intraperitoneal Chemotherapy Combination in Gastric Cancer With Peritoneal Metastasis

This is an open-label, non-randomized, single-center, phase Ib/II study, evaluating efficacy and feasibility of cytoreductive surgery(CRS), extensive peritoneal lavage, hyperthermic intraperitoneal chemotherapy(HIPEC) and post-operative intraperitoneal chemotherapy combination in gastric cancer with peritoneal metastasis

Study Overview

• Status: Completed
• Conditions: Gastric Cancer With Peritoneal Metastasis (PCI<12)
• Intervention / Treatment: Drug: CRS+HIPEC

Detailed Description

Peritoneal metastases in gastric cancer are considered to indicate terminal disease due to poor prognosis because systemic chemotherapy is unlikely to accumulate in peritoneal nodules in cytotoxic concentrations. Cytoreductive surgery (CRS) along with hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested to improve survival in select patients with limited peritoneal spread, resulting in a median overall survival (OS) of 8 to 14 months. It remains unclear, however, which regimen is best and who have benefits from CRS and HIPEC. Herein, we has conducting prospective phase Ib/II trial of CRC and HIPEC with intraperitoneal paclitaxel and cisplatin, and oral S-1 in gastric cancer with peritoneal metastasis.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Department of Surgery, Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient age of 19 years or older and age of 75 years or younger.
2. Histologically proven gastric or esophagogastric junction adenocarcinoma with peritoneal metastasis under diagnostic laparoscopy.
3. Primary tumor measured as resectable in preoperative images.
4. Performance status based on ECOG : 0~1
5. No prior treatment (chemotherapy, radiotherapy, etc.)

6. Adequate hepatic, renal, and hematologic function

   • ANC≥1,500/uL,
   • hemoglobin≥9.0g/dL
   • platelet≥100,000/uL
   • total Bilirubin: ≤ 1.5 × upper normal limit
   • Creatinine<1.5mg/dL
   • AST/ALT, ALP ≤ 2.5 x upper normal limit
7. Patients who can understand this study and sign the consent form.

Exclusion Criteria:

1. Patient who has distant metastasis or para-aortic lymph node metastasis or retroperitoneal metastasis except peritoneal metastasis. (But the patient who has ovarian metastasis with resectable status can be enrolled.)
2. Primary tumor cannot be resected because of direct invasion to other important organ. (But, if the invaded organ can be resected together, such as spleen, gallbladder, distal pancreas, and liver, the patient can be enrolled)
3. HER2 positive patient
4. Patient with active viral infection (for example, HIV, HBV, HCV, except stable status of HBV infection)
5. Pregnant patient, or patient in breast-feeding, or who is planning pregnancy.

6. Patients in exclusion criteria of TS-1, cisplatin, paclitaxel

   • Patients with a history of severe hypersensitivity to these drugs
   • Patients with severe bone marrow depression
   • patients who has severe hepatic, renal disorder
   • patients who has hereditary problem or galactose intolerance, lapp lactase deficiency, or glucose-galactose malabsorption

7. Patients who has important medical problem or infection

   • Cerebrovascular accident(CVA) within 1 year
   • Heart attack within 6 months, uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure(CHF), severe arrhythmia
   • Major operation or injury within 28 days
   • Severe and not recovered wound, ulcer, fracture
   • Uncontrolled bleeding disease
   • Recent active gastric infection
8. Patient with another primary cancer within last 5 years
9. Patient on medication which can interact with the drugs used in this study (fluoropyrimidine-group antineoplastic agents, flucytosine, phenytoin, etc)
10. Patients with other systemic chemotherapy or radiotherapy
11. Patients with psychiatric or neurologic disorder so that he or she cannot understand and sign the consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: anti-cancer drug

Drug: CRS+HIPEC; IbDose-escalation of intraperitoneal paclitaxel will follow a modified 3 + 3 dose escalation procedure.; II① CRS If PCI <12, CRS will be performed by gastrectomy with D2-lymphadenectomy and resection of any involved adjacent structures.If PCI≥12, instead of CRS, 3 times of IP paclitaxel +cisplatin and oral S-1 chemotherapy every 3 weeks, and then PCI <12, CRS will be done.② Extensiveintraperitoneal lavage Peritoneal lavage after CRS will be done with 10 L before HIPEC.③ HIPEC Following surgery HIPEC will be performed using CDDP (60 mg/m2) and PTX (P2RD mg/m2). IP chemotherapy will be performed.④ Post-operative intraperitoneal chemotherapy Postoperative chemotherapy will be done 8 cycles of IP paclitaxel+ cisplatin and oral S-1 after 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ib: Maximum tolerate dose	Ib: To determine the MTD of orally administered S-1 + intraperitoneal paclitaxel +cisplatin in gastric cancer with peritoneal metastasis.	3 months
II: Safety	II:To assess the safety and tolerability of CRS +HIPEC (Clavien-Dindo classification of surgical complication & NCI-common terminology criteria for adverse events(CTC-AE) for chemotherapy]	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS (overall survival)	the length of time from the patient signing the consent form until the patient is still alive	12 months
PFS (Progression-free survival)	the length of time from the patient signing the consent form until the patient shows disease progression	12 months
RR (response rate)	the proportion of complete response to partial response These will be estimated by the Kaplan-Meire method.	12 months

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2017
• Primary Completion (Actual): April 19, 2022
• Study Completion (Actual): May 5, 2022

Study Registration Dates

• First Submitted: December 14, 2016
• First Submitted That Met QC Criteria: December 14, 2016
• First Posted (Estimated): December 19, 2016

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Stomach Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: 4-2016-0252

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No