Chemotherapy Alone vs. Chemotherapy + Surgical Resection in Patients With Limited-metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

• Status: Recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Previously untreated patients with limited metastatic stage (see protocol for details on criteria) will receive 4 cycles of FLOT (5-Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel). Patients without disease progression will be randomized 1:1 to receive additional chemotherapy cycles (4-8 cycles of FLOT) or surgical resection followed by subsequent chemotherapy (4-8 cycles of FLOT). Main objective of the study is overall survival. Most important secondary objective is the quality of life under treatment and during follow-up.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Krankenhaus Nordwest
• Collaborators: Arbeitsgemeinschaft fur Internistische Onkologie; German Research Foundation
• Treatments: Docetaxel; Fluorouracil; Leucovorin; Levoleucovorin; Oxaliplatin; Trastuzumab

Criteria

Inclusion Criteria:

1. Histologically confirmed limited metastatic gastric or GEJ adenocarcinoma.*

2. Medical and technical operability of the primary.

3. Metastatic lesions are resectable or can be controlled by local ablative procedure (central evaluation).

4. No prior chemotherapy and no prior tumor resection.

5. Female and male patients ≥ 18 years. Patients in reproductive age must be willing to use adequate contraception during the study and 3 months after the end of the study (appropriate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of: intrauterine device, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap)). Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start.

6. ECOG (Eastern Cooperative Oncology Group) Performance Status 0 or 1

7. Adequate hematological, hepatic and renal function parameters:

• Leukocytes ≥ 3000/µl

• Platelets ≥ 100,000/µl

• Serum creatinine ≤ 1.5 x upper limit of normal, or glomerular filtration rate (GFR) > 40 ml/min

• Bilirubin ≤ 1.5 x upper limit of normal

• AST (aspartate aminotransferase) and ALT (alanine transaminase) ≤ 3.5 x upper limit of normal

• Alkaline phosphatase ≤ 6 x upper limit of normal

8. Written informed consent of the patient.

(*) Definition of the limited metastatic status is:

1. Retroperitoneal lymph node metastases (RPLM) (e.g., para-aortal, intra-aorto-caval, parapancreatic or mesenterial lymph nodes) only (Note: in duodenum invading gastric cancer, retropancreatic nodes are not regarded M1) or/and

2. at maximum one organ involved with or without RPLM according to the following schema:

I. Localized potentially operable peritoneal carcinomatosis: stage P1 according to classification of the "Japanese Research Society for Gastric Cancer" (Clinically visible carcinomatosis of the peritoneum or of the pleura and >P1 peritoneal carcinomatosis are not allowed!) or II. Liver: maximum of 5 metastatic lesions that are potentially resectable or III. Lung: unilateral involvement, potentially resectable or IV. Uni- or bilateral Krukenberg tumors (ovarian met.) in the absence of macroscopic peritoneal carcinomatosis or V. Uni- or bilateral adrenal gland metastases or VI. Extra-abdominal lymph node metastases such as supraclavicular or cervical lymph node involvement or VII. Localized bone involvement (defined as being within one radiation field) or VIII. Other metastatic disease location that is considered limited by the investigator and is confirmed by the review committee

Exclusion Criteria:

1. Medical inoperability

2. Inability to understand the aims of the study and/or protocol procedures

3. Metastatic disease not fulfilling the criteria of limited disease mentioned in the inclusion criteria or non-metastatic stage (cM0)

4. Cirrhosis of the liver, pronounced alcohol abuse with anticipated detoxification, severe pulmonary infection with considerable reduction of pulmonary function

5. Primary not resectable

6. Hypersensitivity to 5-fluorouracil, leucovorin, oxaliplatin, docetaxel, or trastuzumab (in HER-2 positive tumors)

7. Contraindication versus 5-fluorouracil, leucovorin, oxaliplatin, docetaxel (see specific product information), or trastuzumab (in HER-2 positive tumors)

8. Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA (New York Heart Association) III-IV

9. Clinically significant valvular defect

10. Past or current history of other malignancies unless curatively treated and without evidence of disease for more than 3 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix

11. Known brain metastases

12. Other severe internal disease or acute infection

13. Peripheral polyneuropathy > NCI grade II

14. Serious hepatic impairment (AST/ALT>3.5xULN, AP>6xULN, bilirubin>1.5xULN; ULN = upper limit of normal)

15. Chronic inflammatory bowel disease

16. Any other concurrent antineoplastic treatment including irradiation

17. Participation in another clinical study

18. Pregnancy or lactation