OXALIPLATIN for Rectal cancer | Intermediate and high-risk rectal cancer

Inclusion criteria

• {"criterion_text":"- Male and female patients with histologically confirmed diagnosis of rectal adenocarcinoma localised 0 – 12 cm from the anocutaneous line as measured by rigid rectoscopy (i.e. lower and middle third of the rectum).\n- Staging requirements: High-resolution, thin-sliced (i.e. 3 mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.\n- MRI-defined inclusion criteria: presence of at least one of the following high-risk conditions: any cT3 if the distal extent of the tumor is < 6 cm from the anocutaneous line, or cT3c/d in the middle third of the rectum (≥ 6-12 cm) with MRI evidence of extramural tumor spread into the mesorectal fat of more than 5 mm (>cT3b), or cT3 with clear cN+ based on strict MRI-criteria (see appendix) cT4 tumors, or Tany middle/low third of rectum with clear MRI criteria for N+, mrCRM+ (≤1mm), or Extramural venous invasion (EMVI+).\n- Transrectal endoscopic ultrasound (EUS) is additionally used when MRI is not definitive to exclude early cT1/T2 disease in the lower third of the rectum or early cT3a/b tumors in the middle third of the rectum.\n- Spiral-CT of the abdomen and chest to exclude distant metastases.\n- Aged at least 18 years. No upper age limit.\n- WHO/ECOG Performance Status ≤1.\n- Adequate haematological, hepatic, renal and metabolic function parameters: Leukocytes ≥ 3.000/mm3 , ANC ≥ 1.500/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.\n- Informed consent of the patient."}

Exclusion criteria

• {"criterion_text":"- Lower border of the tumor localised more than 12 cm from the anocutaneous line as measured by rigid rectoscopy.\n- Other concomitant antineoplastic therapy.\n- Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder.\n- Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6 months before enrolment.\n- 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.\n- Known allergic reactions on study medication.\n- Known dihydropyrimidine dehydrogenase deficiency (activity score < 1,5 after genetic testing of DPYD variants)\n- 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).\n- Distant metastases (to be excluded by CT scan of the thorax and abdomen).\n- Prior antineoplastic therapy for rectal cancer.\n- Prior radiotherapy of the pelvic region.\n- Major surgery within the last 4 weeks prior to inclusion.\n- Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.\n- Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).\n- On-treatment participation in a clinical study in the period 30 days prior to inclusion.\n- Previous or current drug abuse."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint of this trial, organ preservation, is defined as follows: survival with rectum intact, no major surgery, no stoma.","definition_or_measurement_approach":"Primary endpoint (organ preservation) defined as survival with rectum intact, no major surgery, no stoma. The endpoint is not reached if any of the following occurs: (1) death, (2) any major surgery other than local excision (R0) performed after randomization, during TNT, at re-staging scheduled 22-24 weeks after start of TNT due to clinical non-cCR, or for any locoregional regrowth after initial cCR requiring salvage-TME, (3) any locoregional regrowth not amenable to salvage surgery, or (4) any stoma (non-re-converted protective stoma within 6 months after completion of TNT, or any stoma needed for toxicity or poor function), whichever occurs first."}

Secondary endpoints

• {"endpoint_text":"- Disease-free survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Rate of clinical complete response after TNT","definition_or_measurement_approach":""}
• {"endpoint_text":"- Rate of immediate TME after TNT","definition_or_measurement_approach":""}
• {"endpoint_text":"- Cumulative incidence of locoregional regrowth after cCR","definition_or_measurement_approach":""}
• {"endpoint_text":"- Rate of salvage surgery (LE/TME with or without APR/stoma) after locoregional regrowth","definition_or_measurement_approach":""}
• {"endpoint_text":"- Cumulative incidence of local recurrence after (salvage) surgery","definition_or_measurement_approach":""}
• {"endpoint_text":"- Postoperative complications of (salvage) surgery","definition_or_measurement_approach":""}
• {"endpoint_text":"- Rate of sphincter-sparing (salvage) surgery","definition_or_measurement_approach":""}
• {"endpoint_text":"- Pathological TNM-staging","definition_or_measurement_approach":""}
• {"endpoint_text":"- R0 resection rate; negative circumferential resection rate","definition_or_measurement_approach":""}
• {"endpoint_text":"- Tumor regression grading according to Dworak","definition_or_measurement_approach":""}
• {"endpoint_text":"- Neoadjuvant rectal score","definition_or_measurement_approach":""}
• {"endpoint_text":"- Quality of TME according to MERCURY","definition_or_measurement_approach":""}
• {"endpoint_text":"- Acute and late toxicity assessment according to NCI CTCAE V.5.0)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Quality of life and functional outcome based on treatment arm and surgical procedures/organ preservation","definition_or_measurement_approach":""}
• {"endpoint_text":"- Cumulative incidence of distant metastases","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Translational / biomarker studies","definition_or_measurement_approach":""}

Germany

Earliest CTIS Part Ii Submission Date

17-09-2024

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

520

Number Of Participants

688

Primary sponsor

Full Name

Goethe University Frankfurt

Organisation Type

Educational Institution

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH","duties_or_roles":"[1,5,6,8]","organisation_type":"Pharmaceutical company"}