Oxaliplatin for Locally advanced rectal cancer | Rectal carcinoma

Inclusion criteria

• {"criterion_text":"- Male and female patients* with histologically confirmed diagnosis of rectal adenocarcinoma localized 0 – 16 cm from the anal verge as measured by rigid rectoscopy (i.e. lower, middle and upper third of the rectum), depending on MRI-defined inclusion criteria (see below). *Thera are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.\n- Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.\n- Transrectal endoscopic ultrasound (EUS) is mandatory and used to help discriminate between T1/2 and early T3 tumors.\n- 4.\tMRI-defined inclusion criteria: - Lower third (0-6 cm): cT1/2 with clear cN+ based on MRI-criteria and cT3a-b (i.e. infiltration up to 5mm into the perirectal fat) (see SOP in chapter 12.3 of the appendix), provided CRM >2mm and EMVI-** (defined as MRI-EMVI score 0-3; see SOP in chapter 12 of the appendix) - Middle third (≥ 6-12 cm): cT1/2 with clear cN+ provided CRM- and EMVI-; cT3 irrespective of the depths of infiltration into the perirectal fat, provided no evidence that tumor is adjacent to (defined as within 2 mm of) the mesorectal fascia on MRI (i.e. CRM > 2 mm), N0 or N1, EMVI-** - Upper third (≥ 12-16 cm): cT1/2 with clear cN+, irrespective of CRM and EMVI; any cT3-4 irrespective of nodal status, CRM and EMVI.\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 hematological, hepatic, renal and metabolic function parameters:\n- Leukocytes ≥ 3.000/mm³, ANC ≥ 2.000/mm³, platelets ≥ 100.000/mm³, Hb > 9 g/dl\n- Serum creatinine ≤ 1.5 x upper limit of normal\n- Bilirubin ≤ 2.0 mg/dl, SGOT-SGPT, and AP ≤ 3 x upper limit of normal.\n- QTc interval (Bazett***) ≤ 440 ms Formula for QTc interval calculation (Bazett): 𝑄𝑇𝑐=𝑄𝑇̅̅̅̅(ms)√ (𝑠𝑒𝑐)=𝑄𝑇̅̅̅̅(ms)√60𝐹𝑒𝑞𝑢𝑒𝑧 (1𝑚𝑖)\n- Informed consent of the patient."}

Exclusion criteria

• {"criterion_text":"- 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 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. ****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).\n- On-treatment participation in a clinical study in the period 30 days prior to inclusion.\n- Previous or current drug abuse.\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 (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 6 months before enrolment.\n- Chronic diarrhea (> grade 1 according NCI CTCAE).\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 or hypersensitivity on study medication or to any of the other excipients.\n- Evidence of peripheral sensory neuropathy > grade 1 according to CTCAE version 5.0 (see appendix).\n- Severe kidney dysfunction (creatinine clearance < 30 ml/min).\n- Recent or concurrent treatment with brivudine.\n- Pernicious or other megaloblastic anaemia caused by vitamin B12 deficiency.\n- Known dihydropyrimidine dehydrogenase deficiency (activity score < 1,5 after genetic testing of DPYD variants).† † For adjustments of chemotherapy for patients with DPYD activity score = 1,5 see Protocol section 4.2.4.3\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)."}

Primary endpoints

• {"endpoint_text":"- The primary endpoint of this trial is disease-free survival, defined as the time from randomisation to one of the following events: no surgery or non-radical (R2) surgery of the primary tumour, locoregional recurrence after R0/1 resection of the primary tumour, second primary colorectal or other cancer, metastatic disease or progression, or death from any cause, whichever occurred first.","definition_or_measurement_approach":"Disease-free survival (DFS): measured as time from randomisation to first of listed events (no surgery or non-radical (R2) surgery of the primary tumour; locoregional recurrence after R0/1 resection; second primary colorectal or other cancer; metastatic disease or progression; or death from any cause)."}

Secondary endpoints

• {"endpoint_text":"- Acute and late toxicity assessment according to NCI CTCAE version 5.0","definition_or_measurement_approach":"Assessed and graded according to NCI CTCAE version 5.0"}
• {"endpoint_text":"- Compliance (completion rate) of chemotherapy","definition_or_measurement_approach":"Measured as chemotherapy completion rate (completion of planned chemotherapy per protocol)"}
• {"endpoint_text":"- Surgical morbidity and complications","definition_or_measurement_approach":""}
• {"endpoint_text":"- Pathological UICC-staging, including pCR (ypT0N0) rate","definition_or_measurement_approach":""}
• {"endpoint_text":"- R0 resection rate; negative circumferential resection rate (CRM > 1mm)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Tumor regression grading according to Dworak in the experimental arm","definition_or_measurement_approach":"Tumor regression grading performed according to Dworak system (as stated)"}
• {"endpoint_text":"- Rate of sphincter-sparing surgery","definition_or_measurement_approach":""}
• {"endpoint_text":"- Rate of W&W with or without local regrowth","definition_or_measurement_approach":""}
• {"endpoint_text":"- Cumulative incidence of local and distant recurrences","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Quality of life and functional outcome based on treatment arm, and surgical procedures","definition_or_measurement_approach":"Quality of life assessments referenced in trial documents (patient-facing QoL forms: QLQ-C30, QLQ-CR29)"}

Germany

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

06-05-2026

Processing Time Days

561

Number Of Participants

550

Primary sponsor

Full Name

Heidelberg University

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":"sponsorDuties codes: 1,5,6,8","organisation_type":"Pharmaceutical company"}