A Phase II Study of Conversion Surgery After IP Paclitaxel With XELOX Chemotherapy in AGC With Peritoneal Dissemination

Peritoneal Carcinomatosis Clinical Trial

Official title:

A Phase II Study Evaluating Efficacy and Safety of Conversion Surgery After Intraperitoneal Paclitaxel in Combination With Systemic Capecitabine and Oxaliplatin Chemotherapy in Advanced Gastric Cancer Patients With Peritoneal Dissemination

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04797923
• Other study ID #: 3-2020-0237
• Status: Recruiting
• Phase: Phase 2
• Start date: December 1, 2019
• Est. completion date: December 30, 2021

Study information

• Verified date: March 2021
• Source: Gangnam Severance Hospital
• Contact: Seung Ho Choi, M.D., Ph.D.
• Phone: 82-2-2019-3374
• Email: choish[@]yuhs.ac
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Advanced gastric cancer combined with peritoneal seeind has dismal prognosis with poor response to systemic chemotherapy and with rapid aggravation of symptoms such as abdominal pain, ileus, and poor nutritional intake. Intraperitoneal (IP) chemotherapy through IP port or catheter has lower complication than HIPEC (hyperthermic intraperitoneal chemotherapy) and can deliver higher dose of chemotherapy with less systemic toxicity. IP chemotherapy combined with systemic chemotehrapy showed benefit in several clinical trials, despite lack of statistical significance in phase 3 clinical trial. Proper dose/combination of chemotherapeutic agents and indication of IP chemotherapy should be investigated through prospective, large-scale clinical trials. Conversion surgery after cytotoxic chemotherapy showed improved survival in retrospective studies. Our hypothesis is that IP chemotherapy combined with systemic chemotherpay (capecitabine + oxaliplatin) would improve success rate of conversion surgery with R0 resection. In the present study, the treatment regimen consists of intraperitoneal paclitaxel combined with oxaliplatin and capecitabine (XELOX), and will be performed following surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 43
• Est. completion date: December 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Histologically or cytologically confirmed advanced gastric cancer adenocarcinoma

2. Peritoneal metastasis histopathologically confirmed by laparoscopy or laparotomy and PCI <12 (including patients with no gross peritoneal lesion and cytology positive)

3. No prior surgery for curative aim and previous chemotherapy for recurrent/metastatic gastric cancer

4. Patient who is willing and able to provide written informed consent/assent for the trial

5. Age between 19 and 75 years

6. Measurable lesion according to RECIST 1.1 criteria

7. ECOG performance status 0-1

8. Have adequate organ function

• ANC = 2,000/uL,
• hemoglobin = 9.0g/dL
• platelet = 100,000/uL
• total Bilirubin: = 1.5 × upper normal limit
• Creatinine = 1.5 × upper normal limit or Creatinine clearance = 60ml/min
• AST/ALT = 3.0 x upper normal limit
• Albumin = 2.5 g/dL
• PT or INR, aPTT = 1.5 × upper normal limit

9. Should agree to use an adequate method of contraception

Exclusion Criteria:

1. Previous systemic chemotherapy for metastatic/recurrent advanced gastric cancer

2. 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.)

3. 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)

4. BMI = 18.5 kg/m2

5. HER2 positive patient (IHC 3+, 2+ with in situ hybridization +)

6. Remnant gastric cancer

7. Intolerable to oral intake of chemotherapeutic agent or have malabsorption syndrome

8. Known additional malignancy that is progressing or requires active treatment in recent 3 years (excluding skin basal cell carcinoma, skin squamous cell carcinoma, thyroid cancer, or in situ cervix cancer that has undergone potentially curative therapy)

9. Symtomatic CNS metastasis and/or leptomeningeal seeding

10. Autoimmune disease in recent 2 years requiring systemic therapy

11. Clinically significant heart disease

12. Peripheral neuropathy = Grade 2

13. Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment

14. History of HIV, HBV, or HCV

Related Conditions & MeSH terms

• Advanced Gastric Cancer
• Carcinoma
• Peritoneal Carcinomatosis
• Peritoneal Neoplasms
• Stomach Neoplasms

Intervention

Drug:
• 1. Treatment: IP chemotherapy + Systemic chemotherapy
1. Treatment: IP chemotherapy + Systemic chemotherapy Day1 + Day 8: IP Paclitaxel 40 mg/m2 every 3 weeks Day1: IV Oxaliplatin 100 mg/m2 every 3 weeks Day 1~14: Capecitabine 1000 mg/m2 PO, BID every 3 weeks

Procedure:
• 2. Response evaluation after 4 cycles of IP + systemic chemotherapy
2. Response evaluation after 4 cycles of IP + systemic chemotherapy Conversion surgery will be done following diagnostic laparoscopy after 4 cycles of IP + systemic chemotherapy. Additional 4 cycles of IP + systemic chemotherapy wille be done following surgery. If surgery is impossible after 4th cycle, four additional cycles of treatment will be done, and convertibility will be evaluated. IP chemotherapy should not exceed total of 8 cycles.

Locations

Country	Name	City	State
Korea, Republic of	Gangnam Severacne Hospital	Seoul	Gangnnam

Sponsors (1)

Lead Sponsor	Collaborator
Gangnam Severance Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of R0 resection	Success rate of conversion surgery (Rate of R0 resection)	30 days after the surgery