Using contact X-ray brachytherapy to preserve the rectum in patients with intermediate rectal cancer

Multicenter Randomized Phase III Trial Evaluating Contact X-ray Brachytherapy for Rectal Preservation in Intermediate Substage Rectal Adenocarcinoma

This study is testing if adding a special type of radiation therapy to standard treatment can help people with intermediate rectal cancer keep their rectum and live longer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 212 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 11 sites (Avignon, France and 10 other locations)
• Trial ID: NCT06402864 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of contact X-ray brachytherapy (CXB) combined with total neoadjuvant therapy (TNT) in patients with intermediate low or mid rectal adenocarcinoma. Participants are randomly assigned to either a control group receiving TNT alone or an experimental group receiving TNT with additional CXB treatments. The primary goal is to assess whether the addition of CXB can improve organ preservation and survival rates in this patient population. Evaluations will be conducted after treatment to determine the best course of action based on clinical response.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed intermediate low or mid rectal adenocarcinoma meeting specific size and staging criteria.

Not a fit: Patients with rectal adenocarcinoma that does not meet the specified intermediate risk criteria or those with significant anal canal involvement may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance survival rates while allowing for rectal preservation in patients with intermediate rectal cancer.

How similar studies have performed: While the use of brachytherapy in rectal cancer is explored, this specific combination with TNT is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* Patient with histologically proven rectal adenocarcinoma
* Intermediate risk factors: size ≥ 3.1 cm and ≤ 6 cm, \< 66% circumference, cT2N1 or T3N0-1, M0 at diagnostic.
* Accessible by digital rectal exam, distal or middle rectum (\<11 cm from anal verge), not significantly involving the anal canal (external sphincter not involved) at diagnostic.
* Operable patient
* Patient who is about to start mFolfirinox chemotherapy. The registration is possible before, during or at the end of 4 cycles of mFolfirinox chemotherapy
* Age ≥ 18 years
* WHO status 0 or 1 at diagnosis
* Biological values within the following limits: Total Bilirubin ≤ 1.5 times the upper limit of normal (ULN); ASAT and ALAT ≤ 5 N; Creatinine ≤ 1.5 N and creatinine clearance\> 60 ml/min; Neutrophils ≥ 1.5. 109 / L; Platelets ≥ 150. 109 / L; Hemoglobin ≥ 9 g / dL (patients can be included even if they have been transfused); Albuminemia≥30g / L before starting mFolfirinox chemotherapy;
* Women of childbearing potential must have a negative serum β-HCG pregnancy test within 15 days prior to the administration of the first study treatment or urine pregnancy 72 hours prior to the administration of the first study treatment.
* Sexually active women of childbearing potential must agree to use a highly effective method of contraception,
* Sexually actives males patients must agree to use condom during the study and for at least 6 months after the last study treatment administration. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception for the same duration.
* Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.
* Patients must be affiliated to a social security system or beneficiary of the same

Exclusion Criteria:

* Other cancer in the 5 years prior to start m Folfirinox chemotherapy or concomitant (except in situ cancer of the cervix, or basal cell carcinoma of the skin).
* History of pelvic irradiation or pelvis surgery
* Early tumor (T1-2N0, size \< 3.1 cm) or advanced tumor (T3 \> 6cm of circumference, T4, N2, M1) at diagnostic
* Patient who stopped mFolfirinox after 3 cycles or less
* Dihydropyrimidine dehydrogenase (DPD) deficiency. The blood uracil level must be measured at screening. The uracilemia dosing result is mandatory prior the inclusion of patient.
* Given the oxaliplatin-related risk of prolongation of QT, patient with hypokalemia less than normal, hypomagnesemia, hypocalcemia, and QT/QTc interval longer than 450 msec for men and longer than 470 msec for women on the inclusion ECG should not be allowed at diagnostic.
* Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction in the last 3 months, significant arrhythmia).
* Unbalanced serious illness, underlying infection likely to prevent the patient from receiving treatment current pregnancy (obligatory pregnancy test at baseline) or breastfeeding.
* Psychiatric illness compromising the understanding of information or the conduct of the study.
* Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.
* Inability to sign informed consent or to undergo medical follow-up of the test for geographical, social or psychological reasons.
* Pregnant or breastfeeding women
* No other anti-tumour prior treatments (chemotherapy, hormone therapy, biologic response inhibitors, targeted therapy) may be used for rectal adenocarcinoma. All live vaccines are prohibited before starting mFolfirinox chemotherapy.
* The combination of warfarin (Coumadine®) with an mFOLFIRINOX regimen, FOLFOX or capecitabine is not recommended. It is preferable to use heparin or LMWH. If warfarin cannot be avoided, more frequent monitoring of prothrombin ratio and INR is necessary.
* Pimozide (Orap®), and cisapride (Prepulsid®) are formally contraindicated: increased risk of ventricular arrhythmias, especially torsades de pointes before starting mFolfirinox chemotherapy
* Known history of hypersensitivity to, fluorouracil, capecitabine, oxaliplatin, irinotecan, folinic acid, or to any of their excipients, according to the SmPCs of these products.
* Recent or concomitant treatment with brivudine, according to the SmPC of fluorouracile and of capecitabine before starting mFolfirinox chemotherapy;
* Chronic inflammatory bowel disease and/or bowel obstruction and in case of concomitant use with St John's Wort, according to the SmPC of irinotecan before starting mFolfirinox chemotherapy;
* Peripheral sensory neuropathy with functional impairment prior to first treatment, according to the SmPC of oxaliplatin before starting mFolfirinox chemotherapy

Where this trial is running

Avignon, France and 10 other locations

• Institut Sainte Catherine — Avignon, France, France (Recruiting)
• Centre Léon Bérard — Lyon, France, France (Recruiting)
• Centre de radiotéhrapie Charcot — Lyon, France, France (Recruiting)
• Hôpital Européen — Marseille, France, France (Recruiting)
• Centre d'oncologie et de radiothérapie — Mâcon, France, France (Recruiting)
• Centre de Haute Energie — Nice, France, France (Recruiting)
• Centre Antoine Lacassagne — Nice, France, France (Recruiting)
• CHU de Saint Etienne — Saint-Etienne, France, France (Recruiting)
• Institut de cancérologie de l'Ouest — Saint-Herblain, France, France (Recruiting)
• Institut Gustave Roussy — Villejuif, France, France (Recruiting)
• Orlam-Bayard — Villeurbanne, France, France (Recruiting)

Study contacts

• Principal investigator: Jérome Durand Labrunie, Dr — Gustave Roussy, Cancer Campus, Grand Paris
• Study coordinator: Jérome Durand Labrunie, Dr

Conditions Adult With Intermediate Low or Mid Rectal Adenocarcinoma