Acronym
STARTREC-3
Name of the study
STARTREC-3: Can we Save the rectum by watchful waiting or transanal microsurgery following shorT-course radiotherapy and Additional local oR systemic Treatment for early-stage REctal Cancer?
Researchers and contact information
Principal investigators:
Prof. dr. J.H.W. de Wilt, dept. Surgery, Radboud University Medical Center
Dr. B.A. Grotenhuis, dept. Surgery, Antoni van Leeuwenhoek
Prof. dr. C.A.M. Marijnen, dept. Radiotherapy, Antoni van Leeuwenhoek
Study coordinator:
Drs. S.E.N de Vries, dept. Surgery, Antoni van Leeuwenhoek & Radboudumc
Plesmanlaan 121, 1066 CX Amsterdam
E: s.d.vries@nki.nl / star-trec@radboudumc.nl
Phone: 020-5129001
Summary study
Objective:
Aim of the STARTREC-3 phase 2 platform study is to improve the organ preservation rate for early-stage rectal cancer: From 60% to at least 80% organ preservation rate at 2 year after onset of treatment (SCRT) for early rectal cancer (cT1-3abN0) and from 30% to at least 60% organ preservation rate at 2 year after onset of treatment (SCRT) for early-intermediate rectal cancer (cT1-3abN1 (≤3 nodes ≤8mm))
Study population: Patients with early-stage rectal cancer, defined as early rectal cancer cT1-3abN0M0 or early-intermediate rectal cancer cT1-3abN1(≤3 nodes ≤8mm)M0, of whom the tumor is ≤40mm in size and located in the mid or distal part of the rectum, and with a wish for organ preservation, can participate in the current study.
Study design: The STARTREC-3 is a non-randomized multicenter phase 2 platform study, which aims to increase organ preservation rates in early-rectal cancer patients by investigating different ways of neoadjuvant treatment intensification. Participating centres have indicated prior to the start of the study in which of the 3 study arms they will include their patients. All arms will start with SCRT, followed by either an additional local radiotherapy boost (either an internal radiotherapy boost by contact X-ray brachytherapy (CXB) or an external beam radiotherapy boost on an MR-guided linear accelerator (EBRT)) or by additional systemic chemotherapy (CTX) in terms of 3 cycles CAPOX. Response evaluations will be performed at certain time intervals to assess the degree of response and to decide whether organ preservation is feasible.
Endpoints: The primary endpoint is the proportion of patients with successful organ preservation at 24 months from the start date of SCRT. Organ preservation is considered to have failed (a) if the rectum is removed; (b) if the patient develops unequivocal locoregional cancer recurrence or (c) if the patient has a stoma. Secondary endpoints include treatment related toxicity, patient reported quality of life, functional and oncological outcomes.
Inclusion criteria:
- Biopsy proven adenocarcinoma of the rectum
- Early- or early-intermediate stage rectal cancer, defined as Magnetic Resonance Imaging (MRI)-T1-3ab, N0/N1 (≤3 mesorectal lymph nodes ≤8mm), MX/M0 rectal tumour
- Maximum tumour diameter ≤40mm (measured from everted edges on sagittal MRI)
- Tumour located in the distal (without extension into the anal canal) or mid-rectum in which TME-surgery is required
- MDT determines that the following treatment options are all reasonable considering tumour details and patient’s characteristics: (a) TME surgery, (b) SCRT, (c) additional radiotherapy boost (internal (CXB) or external (EBRT) boost) and (d) systemic chemotherapy (3 cycles CAPOX)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Age 18 years or older
- Patient able and willing to provide written informed consent for the study
Exclusion criteria:
- Concomitant or previous malignancies within 3 years prior to trial entry, except those that in the opinion of the MDT are unlikely to relapse within 3 years or lead to death within 5 years
- Tumour located in the proximal rectum in which PME-surgery can be performed
- MRI suspicious lymph nodes cN1 (1-3 lymph nodes > 8mm) or cN2
- MRI extramural vascular invasion (mriEMVI) present (defined by protocol guidelines)
- MRI defined mucinous tumour
- Mesorectal fascia threatened by tumour (≤ 1mm on MRI)
- Maximum tumour diameter >40mm (measured from everted edges on sagittal MRI)
- Any form of (endoscopic/surgical) local excision of the primary tumour prior to study-entry
- Prior pelvic radiotherapy
- Definite evidence of regional or distant metastases (M1) in opinion of MDT
- Pre-existing faecal incontinence, leading to an expected impaired quality of life post-treatment
- Pregnant or lactating women
- For study arm 3 (+ additional CAPOX cycles) only: deficient MMR tumours (MSI)
- For study arm 3 (+ additional CAPOX cycles) only: DPD (dihydropyrimidine dehydrogenase) deficiency
Intervention
- ARM 1 CXB boost: A dose of additional 90 Gy is applied in an outpatient setting by means of contact X-ray brachytherapy in 3 fractions of 30 Gy each as an internal boost. CXB will start 2-3 weeks after SCRT, with an interval of 2 weeks between each fraction.
- ARM 2 EBRT boost: Immediately after finishing SCRT, additional 4 fractions of 5 Gy (additional 20 Gy) will be given on the primary tumour as external boost; as EBRT can only be applied by MR Linac or MRIdian, it is recommended to apply the SCRT also by MR Linac/MRIdian.
- ARM 3 CTx: 3 courses of CAPOX (capecitabine b.i.d.1000 mg/m2 (twice daily) day 1-14 every 3 weeks, oxaliplatin 130 mg/m2 day 1 every 3 weeks; adjuvant systemic treatment will start 2-3 week after SCRT.
Participating centres:
- Radboud University Medical Center - opening soon
- Antoni van Leeuwenhoek - open
- Amphia Hospital - opening soon
- Amsterdam University Medical Center - opening soon
- Catharina Hospital Eindhoven - open
- Deventer Hospital - opening soon
- Diakonessenhuis Utrecht - opening soon
- Elisabeth-TweeSteden Hospital - opening soon
- IJselland Hospital - opening soon
- Isala Zwolle - opening soon
- Leiden University Medical Center - opening soon (17-12-2024)
- Martini Hospital - opening soon
- Medical Center Leeuwarden - opening soon
- Rijnstate - opening soon
- Spaarne Gasthuis - opening soon