Status:
RECRUITING
Preoperative FOLFOX Versus Postoperative Risk-adapted Chemotherapy in Patients With Locally Advanced Rectal Cancer
Lead Sponsor:
Ralf Hofheinz
Collaborating Sponsors:
Deutsche Krebshilfe e.V., Bonn (Germany)
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Conditions:
Rectal Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief Summary
This is a multicenter, prospective, randomized, stratified, controlled, open-label study comparing preoperative FOLFOX versus postoperative risk-adapted chemotherapy in patients with locally advanced ...
Detailed Description
Patients with locally advanced rectal cancer are generally treated with preoperative 5-FU- or capecitabine-based chemo-radiotherapy (CRT) and total mesorectal excision (TME) surgery in order to decrea...
Eligibility Criteria
Inclusion
- Male and female patients with histologically confirmed diagnosis of rectal adenocarcinoma localised 0 - 16 cm from the anocutaneous line as measured by rigid rectoscopy (i.e. lower, middle and upper third of the rectum), depending on MRI-defined inclusion criteria (see below).
- Staging requirements: High-resolution magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
- Transrectal endoscopic ultrasound (EUS) is used to help discriminate between T1/2 and early T3 tumors.
- MRI-defined inclusion criteria:
- Lower third (0-6 cm): cT1/2 with clear cN+ based on MRI-criteria (see SOP in chapter 13.3 of the appendix), provided CRM- and EMVI- (defined as MRI-EMVI score 0-3; see SOP in chapter 13.3 of the appendix)
- Middle third (≥ 6-12 cm): cT1/2 with clear cN+ provided CRM- and EMVI-; cT3a/b, i.e. evidence of extramural tumor spread into the mesorectal fat of ≤ 5 mm provided N-, CRM-, and EMVI-
- Upper third (≥ 12-16 cm): cT1/2 with clear cN+ provided CRM- and EMVI-; any cT3-4 irrespective of nodal status.
- Spiral-CT of the abdomen and chest to exclude distant metastases.
- Aged at least 18 years. No upper age limit.
- WHO/ECOG Performance Status ≤1.
- Adequate haematological, hepatic, renal and metabolic function parameters:
- Leukocytes ≥ 3.000/mm³, ANC ≥ 2.000/mm³, platelets ≥ 100.000/mm³, Hb \> 9 g/dl
- Serum creatinine ≤ 1.5 x upper limit of normal
- Bilirubin ≤ 2.0 mg/dl, SGOT-SGPT, and AP ≤ 3 x upper limit of normal.
- QTc interval (Bazett\*\*) ≤ 440 ms
- Informed consent of the patient.
- "\*\*" Formula for QTc interval calculation (Bazett): QTc= ((QT) ̅" (ms)" )/√(RR (sec))= ((QT) ̅" (ms)" )/√(60/(frequency (1/min)))
Exclusion
- Distant metastases (to be excluded by CT scan of the thorax and abdomen).
- Prior antineoplastic therapy for rectal cancer.
- Prior radiotherapy of the pelvic region.
- Major surgery within the last 4 weeks prior to inclusion.
- Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
- Subject (male or female) is not willing to use highly effective\*\*\* methods of contraception during treatment and for 6 months (male or female) after the end of treatment Male patients treated with Oxaliplatin should take legal advice concerning sperm conservation before start of therapy and should additionally use a condom during treatment period. Their female partner of childbearing potential should also use an appropriate contraceptive measure.
- On-treatment participation in a clinical study in the period 30 days prior to inclusion.
- Previous or current drug abuse.
- Other concomitant antineoplastic therapy.
- Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder.
- Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6 months before enrolment.
- Chronic diarrhea (\> grade 1 according NCI CTCAE).
- Prior or concurrent malignancy ≤ 3 years prior to enrolment in study (Exception: non-melanoma skin cancer or cervical carcinoma FIGO stage 0-1), if the patient is continuously disease-free.
- Known allergic reactions or hypersensitivity on study medication or to any of the other excipients.
- Evidence of peripheral sensory neuropathy \> grade 1 according to CTCAE version 5.0 (see appendix).
- Severe kidney dysfunction (creatinine clearance \< 30 ml/min).
- Recent or concurrent treatment with brivudine.
- Pernicious or other megaloblastic anaemia caused by vitamin B12 deficiency.
- Known dihydropyrimidine dehydrogenase deficiency.
- Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (these conditions should be discussed with the patient before registration in the trial).
- "\*\*\*"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; vasectomized partner; sexual abstinence (complete abstinence is defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments).
Key Trial Info
Start Date :
September 30 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
August 1 2030
Estimated Enrollment :
818 Patients enrolled
Trial Details
Trial ID
NCT04495088
Start Date
September 30 2020
End Date
August 1 2030
Last Update
November 18 2023
Active Locations (1)
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1
Unversity Hospital Mannheim
Mannheim, Germany, 68167