Neoadjuvant RCT Versus CT for Patients With Locally Advanced, Potentially Resectable Adenocarcinoma of the GEJ

NCT04375605 | Active Not Recruiting Phase 3 DMC

• 4 other identifiers: RACE2018-001728-20AIO-STO-01182024-516271-32-00
• Study Type: interventional
• Target: 342
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, prospective, randomized, stratified, controlled, open-label study comparing neoadjuvant radiochemotherapy with FLOT versus FLOT chemotherapy alone für patients with locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction (GEJ)

Conditions

Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Comparison of PFS between arms

  to compare PFS in patients with resectable GEJ adenocarcinoma receiving perioperative FLOT alone versus perioperative FLOT combined with neoadjuvant radiochemotherapy where PFS ist defined as the time from randomization to disease progression or disease recurrence after surgery or death from any cause

  up to 5 years

Secondary Outcomes (7)

• Overall survival (OS)

  up to 5 years

• R0 resection rate

  after surgery, approx. 12 weeks after randomization

• Number of harvested lymph nodes

  after surgery, approx. 12 weeks after randomization

• Site of tumor relapse

  5 years

• Overall survival rate at 1, 3 and 5 years

  1 year, 3 years, 5 years

Study Arms (2)

Arm A (control arm)

ACTIVE COMPARATOR

Patients randomized in control arm A will receive four cycles of neoadjuvant chemotherapy with FLOT every two weeks (5-FU 2600 mg/m² d1, folinc acid 200 mg/m² d1, oxaliplatin 85 mg/m² d1, docetaxel 50 mg/m² d1) followed by surgical resection 4-6 weeks after day 1 of the last cycle of neoadjuvant therapy. 6-12 weeks after surgery adjuvant chemotherapy starts with 4 cycles of FLOT (total treatment period 25-32 weeks).

Drug: 5-Fluorouracil; Drug: Calcium folinate; Drug: Oxaliplatin; Drug: Docetaxel

Arm B (experimental arm)

EXPERIMENTAL

Patients randomized in experimental arm B will receive two cycles of neoadjuvant induction chemotherapy with FLOT (5-FU 2600 mg/m² d1, folinic acid 200 mg/m² d1, oxaliplatin 85 mg/m² d1, docetaxel 50 mg/m² d1) every two weeks (4 weeks of therapy) followed by radiochemo-therapy beginning at day 21 after day one of the last cycle of chemotherapy. Radiochemotherapy consists of oxaliplatin 45 mg/m² weekly (d1, 8, 15, 22, 29) and continuous infusional 5-FU 225 mg/m² plus concurrent radiotherapy given in 5/week fractions with 1.8 Gy to a dose of 45 Gy over 5 weeks. Resection is performed 4-6 weeks after last treatment with chemotherapy / radiation. Adjuvant treatment starts 6-12 weeks after surgery and consists of 4 cycles of FLOT (total treatment period of 26 - 33 weeks).

Drug: 5-Fluorouracil; Drug: Calcium folinate; Drug: Oxaliplatin; Drug: Docetaxel; Radiation: Radiation; Drug: Oxaliplatin during radiotherapy; Drug: 5-Fluorouracil during radiotherapy

Interventions

5-Fluorouracil DRUG

Day 1 q2w: 2600 mg/m² IV over 24 hours

Arm A (control arm); Arm B (experimental arm)

Calcium folinate DRUG

Day 1 q2w: 200 mg/m² IV over 2 hours

Also known as: Folinic Acid

Arm A (control arm); Arm B (experimental arm)

Oxaliplatin DRUG

Day 1 q2w: 85 mg/m² IV over 2 hours

Arm A (control arm); Arm B (experimental arm)

Docetaxel DRUG

Day 1 q2w: 50 mg/m² IV over 2 hours

Arm A (control arm); Arm B (experimental arm)

Radiation RADIATION

25 fractions (5 each week over 5 weeks) each 1,8 Gy to a total of 45 Gy

Arm B (experimental arm)

Oxaliplatin during radiotherapy DRUG

Day 1, 8, 15, 22, 29: 45 mg/m² IV over 2 hours

Arm B (experimental arm)

5-Fluorouracil during radiotherapy DRUG

day 1 - 33: 225 mg/m²/day IV continuously

Arm B (experimental arm)

Eligibility Criteria

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

You may qualify if:

• Histologically proven, locally advanced and potentially resectable adenocarcinoma of the gastroesophageal junction (GEJ) (Siewert I- III) that is: cT3-4, any N, M0 or cT2 N+, M0 according to AJCC 8th edition
• Patients\* must be candidates for potential curative resection as determined by the treating surgeon
• ECOG performance status 0-1
• Age 18 years or above
• Adequate hematologic function with absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/l, platelets ≥ 100 x 10\^9/l and hemoglobin ≥ 9.0 mg/dl
• INR \<1.5 and aPTT\<1.5 x upper limit of normal (ULN) within 7 days prior to randomization
• Adequate liver function as measured by serum transaminases (ASAT, ALAT) ≤ 2.5 x ULN and total bilirubin ≤ 1.5 x ULN
• Adequate renal function with serum creatinine ≤ 1.5 x ULN
• QTc interval (Bazett\*) ≤ 440 ms
• Written informed consent obtained before randomization
• Negative pregnancy test for women of childbearing potential within 7 days of commencing study treatment. Males and females of reproductive potential must agree to practice highly effective\*\*\* contraceptive measures during the study and for 6 months after the end of study treatment. Male patients must also agree to refrain from father a child during treatment and up to 6 months afterwards and additionally to use a condom during treatment period. Their female partner of childbearing potential must also agree to use an adequate contraceptive measure.
• \*There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.
• \*\* formula for QTc interval calculation (Bazett): QTc= ((QT) ̅" (ms)" )/√(RR (sec))= ((QT) ̅" (ms)" )/√(60/(Frequence (1/min)))
• \*\*\* highly effective (i.e. failure rate of \<1% per year when used consistently and correctly) methods: intravaginal and transdermal combined (estrogen and progestogen containing) hormonal contraception; injectable and implantable progestogen-only hormonal contraception; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence (complete abstinence is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments).

You may not qualify if:

• Past or current history (within the last 5 years prior to treatment start) of other malignancies. Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible
• Evidence of peripheral sensory neuropathy \> grade 1 according to CTCAE version 4.03
• Patients with other significant underlying medical conditions that may be aggravated by the study treatment or are not controlled
• Pregnant or lactating females
• Patients medically unfit for chemotherapy and radiotherapy
• Patients receiving any immunotherapy, cytotoxic chemotherapy or radiotherapy other than defined by the protocol. The participation in another clinical trial with the use of investigational agents, chemotherapy or radiotherapy during the trial is not permitted
• Known hypersensitivity against 5-FU, folinc acid, oxaliplatin or docetaxel
• Other known contraindications against 5-FU, folinic acid, oxaliplatin, or docetaxel
• Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA III-IV
• Clinically significant valvular defect
• Other severe internal disease or acute infection
• Peripheral polyneuropathy \> NCI Grade II according to CTCAE version 4.03
• Chronic inflammatory bowel disease

Sponsors & Collaborators

• Universitätsmedizin Mannheim: lead
• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: collaborator
• Deutsche Krebshilfe e.V., Bonn (Germany): collaborator

Study Sites (1)

Unversity Hospital Mannheim

Mannheim, 68167, Germany

Location

Related Publications (1)

• Lorenzen S, Biederstadt A, Ronellenfitsch U, Reissfelder C, Monig S, Wenz F, Pauligk C, Walker M, Al-Batran SE, Haller B, Hofheinz RD. RACE-trial: neoadjuvant radiochemotherapy versus chemotherapy for patients with locally advanced, potentially resectable adenocarcinoma of the gastroesophageal junction - a randomized phase III joint study of the AIO, ARO and DGAV. BMC Cancer. 2020 Sep 15;20(1):886. doi: 10.1186/s12885-020-07388-x.

  PMID: 32933498 DERIVED

MeSH Terms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Docetaxel; Radiation

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; Physical Phenomena

Study Officials

• Ralf-Dieter Hofheinz, Prof. Dr.

  Universitätsmedizin Mannheim

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: May 5, 2020
• Study Start: June 3, 2020
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 7, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)