Comparing preoperative chemotherapy alone to chemotherapy with radiotherapy for rectal cancer

Non Inferiority Multicenter Phase III Randomized Trial Comparing Preoperative Chemotherapy Only to Chemotherapy Followed by Chemoradiotherapy for Locally Advanced Resectable Rectal Cancer (Intergroup FRENCH-GRECCAR- PRODIGE)

This study is testing whether chemotherapy alone before surgery is just as effective as chemotherapy combined with radiation for people with locally advanced rectal cancer.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 540 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Le Kremlin-Bicêtre, Île-de-France Region)
• Trial ID: NCT03875781 on ClinicalTrials.gov

What this trial studies

This phase III non-inferiority trial aims to compare the effectiveness of preoperative chemotherapy using modified FOLFIRINOX alone against a combination of chemotherapy followed by chemoradiotherapy in patients with locally advanced rectal cancer. The study will enroll 540 patients across 42 academic centers in France, randomizing them into two treatment arms. The primary endpoint is the 3-year progression-free survival rate, with a focus on assessing the overall treatment strategy's effectiveness. Patients will undergo reassessment with MRI after the preoperative treatment and before surgery to evaluate their response.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically proven mid or low rectal carcinoma that is resectable and meets specific imaging criteria.

Not a fit: Patients with rectal tumors larger than 10 cm from the anal verge or those with cT4 tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide an effective treatment option that avoids the need for pelvic irradiation, potentially reducing side effects for patients with rectal cancer.

How similar studies have performed: Other studies have shown success with similar chemotherapy approaches, but this specific comparison of preoperative chemotherapy alone versus combined treatment is novel.

Eligibility criteria

Inclusion Criteria:

* Histologically proven middle or low rectal carcinoma, ≤ 10 cm from the anal verge on MRI (sagittal slide)
* cT3N0 and/or cT1-T3N+ on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound),
* Pretreatment predictive circumferential margin \> 2mm on pretreatment imaging work up (pelvic contrast enhanced MRI)
* Patients must be 18 years old or older
* A World Health Organization (WHO/ECOG) performance status of 0 or 1
* Informed consent signed
* Patients of childbearing / reproductive potential should use adequate birth control measures during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

Exclusion Criteria:

* Rectal tumor \> 10 cm from the anal verge on MRI (sagittal slide)
* cT4 tumor on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound) or involvement of external sphincter
* Circumferential margin ≤ 2 mm on pretreatment imaging work up (pelvic contrast enhanced MRI)
* Metastatic disease
* Prior pelvic irradiation or any contraindication to pelvic irradiation
* Contraindication to oxaliplatin or irinotecan or 5FU based chemotherapy
* Concomitant treatment with warfarin is contraindicated and warafarin must be replaced whenever possible to allow for inclusion.
* Recent or concomitant treatment with brivudine is contraindicated
* contraindications to 5-FU: complete and permanent insufficiency in dihydropyrimidine dehydrogenase, bone marrow insufficiency, chronic and severe infection
* contraindication to irinotecan : inflammatory bowel disease, bilirubin serum level \> 3 times the upper limit of the normal rate, severe bone marrow insufficiency, WHO/ECOG performence status \> 2,
* Concomitant treatment with millepertuis.
* contraindication to oxaliplatin :

  \*bone marrow insufficiency before treatment initiation (neutrophil count \<2x109/L and/or platelet count \<100x109/L), peripheral neuropathy with permanent invalidity before treatment initiation
* severe renal insufficiency (Creatinin clearance \<30 ml/min)
* contraindications to folinic acid : Biermer anemia and other anemia related to B12 vitamin insufficiency
* contraindications to capecitabin : severe renal insufficiency (Creatinin clearance \<30 ml/min), complete and permanent insufficiency in dihydropyrimidine dehydrogenase
* live attenuated vaccine should not be used during and 6 months after preoperative treatment.
* Previous colorectal cancer
* Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for \>5 years
* Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
* protected adults
* Pregnancy or breastfeeding
* Patient with no national health or universal plan affiliation coverage.

Where this trial is running

Le Kremlin-Bicêtre, Île-de-France Region

• BENOIST — Le Kremlin-Bicêtre, Île-de-France Region, France (RECRUITING)

Study contacts

• Study coordinator: Stéphane BENOIST, MD,PHD

Conditions: Rectal Cancer, Advanced Cancer, Rectal cancer, FOLFIRINOX,, chemotherapy, radiochemotherapy, surgery