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FOLFOX before surgey compared to risk-adapted chemotherapy after surgery in patients with locally advanced rectal cancer and low risk for local failure
EU CTIS ID: 2024-518077-34-00
What this study is testing
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. We hypothesize that the 3-year DFS probability would improve from 76% in the standard arm to 85% in the investigational arm (hazard ratio of 0.60). With a power of 90% at a two-sided significance level of 5%, the sample size required to obtain a statistically significant difference is 550 patients (161 events) in total.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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.
- 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 Formula for QTc interval calculation (Bazett): 𝑄𝑇𝑐=𝑄𝑇̅̅̅̅(ms)√ (𝑠𝑒𝑐)=𝑄𝑇̅̅̅̅(ms)√60𝐹𝑒𝑞𝑢𝑒𝑧 (1𝑚𝑖)
- Informed consent of the patient.
- Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
You likely can't join if
- Distant metastases (to be excluded by CT scan of the thorax and abdomen).
- Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder.
- Clinically significant cardiovascular disease (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.
See the full eligibility criteria
Who can join
- 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.
- 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 Formula for QTc interval calculation (Bazett): 𝑄𝑇𝑐=𝑄𝑇̅̅̅̅(ms)√ (𝑠𝑒𝑐)=𝑄𝑇̅̅̅̅(ms)√60𝐹𝑒𝑞𝑢𝑒𝑧 (1𝑚𝑖)
- Informed consent of the patient.
- Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
- Transrectal endoscopic ultrasound (EUS) is mandatory and 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 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.
- 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 hematological, hepatic, renal and metabolic function parameters:
- Leukocytes ≥ 3.000/mm³, ANC ≥ 2.000/mm³, platelets ≥ 100.000/mm³, Hb > 9 g/dl
What rules you out
- Distant metastases (to be excluded by CT scan of the thorax and abdomen).
- Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder.
- Clinically significant cardiovascular disease (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 (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
- Prior antineoplastic therapy for rectal cancer.
- 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).
- 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. ****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).
- On-treatment participation in a clinical study in the period 30 days prior to inclusion.
- Previous or current drug abuse.
- Other concomitant antineoplastic therapy.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.