Overview

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

Status:
Recruiting

Trial end date:
2028-08-01

Target enrollment:
0

Participant gender:
All

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)

Phase:

Phase 3

Accepts Healthy Volunteers?

Details

Lead Sponsor:

Universitätsmedizin Mannheim

Collaborators:

Deutsche Krebshilfe e.V., Bonn (Germany)
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Treatments:

Calcium
Docetaxel
Fluorouracil
Leucovorin
Levoleucovorin
Oxaliplatin

Criteria

Inclusion Criteria:

1. 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

2. Patients* must be candidates for potential curative resection as determined by the
treating surgeon

3. ECOG performance status 0-1

4. Age 18 years or above

5. 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

6. INR <1.5 and aPTT<1.5 x upper limit of normal (ULN) within 7 days prior to
randomization

7. Adequate liver function as measured by serum transaminases (ASAT, ALAT) ≤ 2.5 x ULN
and total bilirubin ≤ 1.5 x ULN

8. Adequate renal function with serum creatinine ≤ 1.5 x ULN

9. QTc interval (Bazett*) ≤ 440 ms

10. Written informed consent obtained before randomization

11. 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).

Exclusion Criteria:

1. Evidence of metastatic disease (exclusion of distant metastasis by CT of thorax and
abdomen, bone scan or MRI [if osseous lesions are suspected due to clinical signs])

2. 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

3. Evidence of peripheral sensory neuropathy > grade 1 according to CTCAE version 4.03

4. Patients with other significant underlying medical conditions that may be aggravated
by the study treatment or are not controlled

5. Pregnant or lactating females

6. Patients medically unfit for chemotherapy and radiotherapy

7. 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

8. Known hypersensitivity against 5-FU, folinc acid, oxaliplatin or docetaxel

9. Other known contraindications against 5-FU, folinic acid, oxaliplatin, or docetaxel

10. Clinically significant active coronary heart disease, cardiomyopathy or congestive
heart failure, NYHA III-IV

11. Clinically significant valvular defect

12. Other severe internal disease or acute infection

13. Peripheral polyneuropathy > NCI Grade II according to CTCAE version 4.03

14. Chronic inflammatory bowel disease