eoadjuvant Radiochemotherapy versus Chemotherapy for Patients with Locally Advanced, Potentially Resectable Adenocarcinoma of the Gastroesophageal Junction (GEJ).
- Conditions
- ocally Advanced, Potentially Resectable Adenocarcinoma of the Gastroesophageal Junction (GEJ)MedDRA version: 20.1Level: PTClassification code 10062878Term: Gastrooesophageal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-001728-20-DE
- Lead Sponsor
- Ruprecht-Karls-Universität Heidelberg
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 340
1.Histologically proven, locally advanced and potentially resectable adenocarcinoma of the gastroesophageal junction (GEJ) (Siewert I- III) that is: cT3-4, any N, 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) given in protocol
***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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 340
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 340
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 (see appendix)
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, folinic 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine if adding radiochemotherapy to neoadjuvant chemotherapy before undergoing oncologically adequate resection improves progression free survival of patients with resectable GEJ adenocarcinoma<br>;Secondary Objective: • To evaluate overall survival, including survival rates after 1, 3 and 5 years<br>• To assess the R0 resection rate<br>• To assess the number of lymph nodes harvested during surgery<br>• To determine the site of tumor relapse<br>• To assess the perioperative morbidity and mortality rate<br>• To assess Safety and toxicity by NCI CTC criteria<br>• To assess the quality of life (QoL) by using the EORTC QLQ-C30 and the esophagogastric module OG25;Primary end point(s): Progression-free survival (PFS) due to the addition of preoperative radiochemotherapy compared to perioperative chemotherapy alone in patients undergoing oncologically adequate surgery in the treatment of resectable GEJ adenocarcinoma;Timepoint(s) of evaluation of this end point: After surgery
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Overall survival, including survival rates after 1, 3 and 5 years<br>R0 resection rate<br>Number of harvested lymph nodes<br>Site of tumor relapse<br>Perioperative morbidity and mortality rate<br>Satefy and toxicity by NCI CTC criteria<br>Quality of life (QoL) by using the EORTC QLQ-C30 and the esophagogastric module OG25;Timepoint(s) of evaluation of this end point: Overall survival, including survival rates: after 1, 3 and 5 years<br>R0 resection rate: after surgery<br>Number of harvested lymph nodes: after surgery<br>Site of tumor relapse.<br>Perioperative morbidity and mortality rate: after surgery<br>Satefy and toxicity by NCI CTC criteria<br>Quality of life (QoL) by using the EORTC QLQ-C30 and the esophagogastric module OG25