Preoperative FOLFOX Versus Postoperative Risk-adapted Chemotherapy in Patients With Locally Advanced Rectal Cancer

• Status: Recruiting
• Trial end date: 2030-08-01
• Target enrollment: 0
• Participant gender: All

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 rectal cancer and low risk for local failure

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ralf Hofheinz
• Collaborators: Deutsche Krebshilfe e.V., Bonn (Germany); German Rectal Cancer Study Group; Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
• Treatments: Capecitabine; Fluorouracil; Folic Acid; Leucovorin; Levoleucovorin; Oxaliplatin

Criteria

Inclusion Criteria:

1. 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).

2. Staging requirements: High-resolution magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.

3. Transrectal endoscopic ultrasound (EUS) is used to help discriminate between T1/2 and early T3 tumors.

4. 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.

5. Spiral-CT of the abdomen and chest to exclude distant metastases.

6. Aged at least 18 years. No upper age limit.

7. WHO/ECOG Performance Status ≤1.

8. Adequate haematological, hepatic, renal and metabolic function parameters:

9. Leukocytes ≥ 3.000/mm³, ANC ≥ 2.000/mm³, platelets ≥ 100.000/mm³, Hb > 9 g/dl

10. Serum creatinine ≤ 1.5 x upper limit of normal

11. Bilirubin ≤ 2.0 mg/dl, SGOT-SGPT, and AP ≤ 3 x upper limit of normal.

12. QTc interval (Bazett**) ≤ 440 ms

13. Informed consent of the patient.

"**" Formula for QTc interval calculation (Bazett): QTc= ((QT) ̅" (ms)" )/√(RR (sec))= ((QT) ̅" (ms)" )/√(60/(frequency (1/min)))

Exclusion Criteria:

1. Distant metastases (to be excluded by CT scan of the thorax and abdomen).

2. Prior antineoplastic therapy for rectal cancer.

3. Prior radiotherapy of the pelvic region.

4. Major surgery within the last 4 weeks prior to inclusion.

5. Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.

6. 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.

7. On-treatment participation in a clinical study in the period 30 days prior to inclusion.

8. Previous or current drug abuse.

9. Other concomitant antineoplastic therapy.

10. Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder.

11. Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6 months before enrolment.

12. Chronic diarrhea (> grade 1 according NCI CTCAE).

13. 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.

14. Known allergic reactions or hypersensitivity on study medication or to any of the other excipients.

15. Evidence of peripheral sensory neuropathy > grade 1 according to CTCAE version 5.0 (see appendix).

16. Severe kidney dysfunction (creatinine clearance < 30 ml/min).

17. Recent or concurrent treatment with brivudine.

18. Pernicious or other megaloblastic anaemia caused by vitamin B12 deficiency.

19. Known dihydropyrimidine dehydrogenase deficiency.

20. 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).