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

NCT02578368 | Completed Phase 3 DMC

• 1 other identifier: RENAISSANCE
• Study Type: interventional
• Target: 183
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastric Cancer

Keywords

gastric cancer; perioperative; FLOT; limited metastatic; GEJ cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  up to 5 years follow-up

Secondary Outcomes (8)

• Quality of life (QoL) adjusted OS

  up to 5 years follow-up

• QoL-response

  up to 5 years follow-up

• QoL mean scores

  up to 5 years follow-up

• OS in patients with lymph node metastases only

  up to 5 years follow-up

• Progression free survival (PFS)

  up to 5 years follow-up

Study Arms (2)

Arm A: FLOT chemotherapy + surgery (OP)

EXPERIMENTAL

4 cycles (8 weeks) FLOT pre-OP - surgery - 4-8 cycles FLOT (8-16 weeks) post-OP Docetaxel (50 mg/m2) in 250 ml sodium chloride (NaCl) 0.9% i.v. for 1 h, d1; Oxaliplatin (85 mg/m2) in 500 ml G5% (glucose 5%) i.v. for 2 h, d1; Leucovorin (Ca-folinate) (200 mg/m2) in 250 ml NaCl 0.9% i.v. for 1 h, d1\*; 5-FU (2600 mg/m2) continuous infusion for 24 h, d1; Repeated every two weeks (qd15). \* Leucovorin can be replaced by sodium folinate. Dose adjustment necessary if levo-leucovorin is used instead of racemic leucovorin mixture. For HER-2 positive disease, trastuzumab should be added: Trastuzumab 4 mg/kg body weight (6 mg loading dose at 1st administration), i.v. for 1 h, d1 For PD-L1 positive disease (CPS ≥ 5), nivolumab can be added according to SmPC: Nivolumab 240 mg i.v. for 30 min, d1, repeated every two weeks (q15d)

Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel; Drug: Trastuzumab; Drug: sodium folinate; Procedure: Surgery

Arm B: FLOT chemotherapy alone

ACTIVE COMPARATOR

4 cycles (8 weeks) FLOT followed by further 4-8 cycles FLOT (8-16 weeks) Docetaxel (50 mg/m2) in 250 ml sodium chloride (NaCl) 0.9% i.v. for 1 h, d1; Oxaliplatin (85 mg/m2) in 500 ml G5% (glucose 5%) i.v. for 2 h, d1; Leucovorin (Ca-folinate) (200 mg/m2) in 250 ml NaCl 0.9% i.v. for 1 h, d1\*; 5-FU (2600 mg/m2) continuous infusion for 24 h, d1; Repeated every two weeks (qd15). \* Leucovorin can be replaced by sodium folinate. Dose adjustment necessary if levo-leucovorin is used instead of racemic leucovorin mixture. For HER-2 positive disease, trastuzumab should be added: Trastuzumab 4 mg/kg body weight (6 mg loading dose at 1st administration), i.v. for 1 h, d1 For PD-L1 positive disease (CPS ≥ 5), nivolumab can be added according to SmPC: Nivolumab 240 mg i.v. for 30 min, d1, repeated every two weeks (q15d)

Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Docetaxel; Drug: Trastuzumab; Drug: sodium folinate

Interventions

5-Fluorouracil DRUG

2600 mg/m², d1 i.v., every 2 weeks

Also known as: 5-FU

Arm A: FLOT chemotherapy + surgery (OP); Arm B: FLOT chemotherapy alone

Leucovorin DRUG

200 mg/m², d1, i.v., every 2 weeks

Also known as: calcium folinate

Arm A: FLOT chemotherapy + surgery (OP); Arm B: FLOT chemotherapy alone

Oxaliplatin DRUG

85 mg/m², d1, i.v., every 2 weeks

Arm A: FLOT chemotherapy + surgery (OP); Arm B: FLOT chemotherapy alone

Docetaxel DRUG

50mg/m², d1, i.v., every 2 weeks

Arm A: FLOT chemotherapy + surgery (OP); Arm B: FLOT chemotherapy alone

Trastuzumab DRUG

4 mg/kg BW (6 mg loading dose at 1st administration), i.v. for 1 h, d1, i.v., every two weeks

Arm A: FLOT chemotherapy + surgery (OP); Arm B: FLOT chemotherapy alone

sodium folinate DRUG

can be used to replace leucovorin (calcium folinate)

Arm A: FLOT chemotherapy + surgery (OP); Arm B: FLOT chemotherapy alone

Surgery PROCEDURE

Aim of surgical resection is a complete (R0) resection of the primary tumor and the metastases or a complete macroscopic cytoreduction of the metastases.

Arm A: FLOT chemotherapy + surgery (OP)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed limited metastatic gastric or GEJ adenocarcinoma.\*
• Medical and technical operability of the primary.
• Metastatic lesions are resectable or can be controlled by local ablative procedure (central evaluation).
• No prior chemotherapy and no prior tumor resection.
• 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.
• ECOG (Eastern Cooperative Oncology Group) Performance Status 0 or 1
• 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
• Written informed consent of the patient.
• (\*) Definition of the limited metastatic status is:

You may not qualify if:

• Medical inoperability
• Inability to understand the aims of the study and/or protocol procedures
• Cirrhosis of the liver, pronounced alcohol abuse with anticipated detoxification, severe pulmonary infection with considerable reduction of pulmonary function
• Primary not resectable
• Hypersensitivity to 5-fluorouracil, leucovorin, oxaliplatin, or docetaxel
• Contraindication versus 5-fluorouracil, leucovorin, oxaliplatin, or docetaxel (see specific product information)
• Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA (New York Heart Association) III-IV
• Clinically significant valvular defect
• 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
• Known brain metastases
• Other severe internal disease or acute infection
• Peripheral polyneuropathy \> NCI grade II
• Serious hepatic impairment (AST/ALT\>3.5xULN, AP\>6xULN, bilirubin\>1.5xULN; ULN = upper limit of normal)
• Chronic inflammatory bowel disease
• Any other concurrent antineoplastic treatment including irradiation

Sponsors & Collaborators

• Krankenhaus Nordwest: lead
• German Research Foundation: collaborator
• Arbeitsgemeinschaft fur Internistische Onkologie: collaborator

Study Sites (1)

Krankenhaus Nordwest

Frankfurt am Main, 60488, Germany

Location

Related Publications (1)

• Al-Batran SE, Goetze TO, Mueller DW, Vogel A, Winkler M, Lorenzen S, Novotny A, Pauligk C, Homann N, Jungbluth T, Reissfelder C, Caca K, Retter S, Horndasch E, Gumpp J, Bolling C, Fuchs KH, Blau W, Padberg W, Pohl M, Wunsch A, Michl P, Mannes F, Schwarzbach M, Schmalenberg H, Hohaus M, Scholz C, Benckert C, Knorrenschild JR, Kanngiesser V, Zander T, Alakus H, Hofheinz RD, Roedel C, Shah MA, Sasako M, Lorenz D, Izbicki J, Bechstein WO, Lang H, Moenig SP. The RENAISSANCE (AIO-FLOT5) trial: effect of chemotherapy alone vs. chemotherapy followed by surgical resection on survival and quality of life in patients with limited-metastatic adenocarcinoma of the stomach or esophagogastric junction - a phase III trial of the German AIO/CAO-V/CAOGI. BMC Cancer. 2017 Dec 28;17(1):893. doi: 10.1186/s12885-017-3918-9.

  PMID: 29282088 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Docetaxel; Trastuzumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Salah-Eddin Al-Batran, MD

  Institute of Clinical Cancer Research (IKF), Krankenhaus Nordwest; University Cancer Center Frankfurt (UCT)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 16, 2015
• Study Start: February 1, 2016
• Primary Completion: August 27, 2024
• Study Completion: August 27, 2024
• Last Updated: November 12, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)