Interest of PET-MRI in the Evaluation of the Response After Neoadjuvant Treatment of Locally Advanced Rectal Adenocarcinoma

Study Overview
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Brief Summary
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With 50 patients included, this trial would be the largest pilot study evaluating the value of MRI PET in locally advanced rectal cancer. On the other hand, it would be the only pilot study performing several MRI PET during neoadjuvant treatment. Presumably, the response assessed at the 2nd MRI PET (before cycle 4 or induction chemotherapy) would be predictive of the overall response at the end of neoadjuvant treatment. Then, it would be possible to predict precociously the tumor response.

Detailed Description
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The management of localized rectal cancer is done in two phases. The first phase, medical, combines a possible first chemotherapy, followed by a concomitant chemoradiotherapy. The second phase, 6 to 8 weeks later, consists of surgery of the rectum. Magnetic resonance imaging (MRI) of the pelvis allows staging of the tumor and its possible lymph node extensions. MRI can also be used to assess tumor response after the first phase of treatment and before surgery. But MRI of the pelvis is partially imperfect. PET-MRI is an examination that combines MRI with an injection of [18 F]fluorodeoxyglucose (18F-FDG). It is known to be more sensitive in assessing tumor stage and lymph node extensions compared to MRI and more sensitive in assessing tumor response before surgery. The aim of this study is to determine predictive parameters for response to the first phase of treatment by accurately identifying the characteristics of tumors that have responded or not to treatment with chemotherapy and chemoradiotherapy.

Official Title
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Interest of PET-MRI in the Evaluation of the Response After Neoadjuvant Treatment of Locally Advanced Rectal Adenocarcinoma

Conditions
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Rectal Cancer

Intervention / Treatment
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* Other: PET-MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) 0 to 2 Histologically proven rectal cancer clinical tumor classification (cT) : cT3 - cT4 or all T / N+ / M0 Tumor resectable or considered resectable after chemoradiotherapy Decision chemotherapy followed by neoadjuvant chemoradiotherapy decided at the organ Multidisciplinary Meeting Absence of distant metastases Adequate contraception for women of childbearing potential Adequate hematologic function Adequate liver function Free, signed and informed consent For women of childbearing potential : negative pregnancy test Exclusion Criteria: Subject with Uncontrolled diabetes Contraindication to surgery Contraindication to MRI Contraindication to PET scan Contraindication to chemotherapy History of pelvic radiotherapy History of major co-morbidity that may prevent treatment and no active infection (HIV or chronic hepatitis B or C) Hypofractionated radiotherapy according to the Swedish protocol (25 Gy in 5 fractions) Colloid (mucinous) adenocarcinoma Presence of distant metastases Contraindication to 5-FluoroUracil (FU), oxaliplatin or irinotecan History of known Gilbert's disease Patient with known UGT1A1 genotype Known Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency Medical history of chronic diarrhea or inflammatory disease of the colon or rectum Medical history of angina or myocardial infarction. Active progressive infection or any other serious medical condition that could compromise the administration of the treatment Other concurrent cancer, or medical history of cancer other than treated in situ cervical carcinoma or basal cell carcinoma or squamous cell carcinoma Patient enrolled in another clinical trial testing an investigational agent Pregnant or breastfeeding woman Persons deprived of their freedom or under guardianship or incapable of giving consent Any psychological, familial, sociological or geographic condition that may interfere with the study protocol or follow-up schedule

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult population with rectal cancer<br> | Other: PET-MRI<br>* Each patient will have a pre-treatment PET-MRI (PET-MRI 1) within 21 days before the start of treatment. Induction chemotherapy may be performed at another center than the investigating center. After 3 cycles of induction chemotherapy and before the 4th cycle, a second PET MRI (PET MRI 2) will be performed. In patients who have received less than 3 cycles of induction chemotherapy, this mid-therapy PET-MRI will not be performed. A 3rd PET-MRI will be performed prior to radiation therapy (PET-MRI 3). A final MRI PET (MRI PET 4) will take place before surgery. A total of 4 PET MRI scans will be performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of the correlation between the PET-MRI changes after neo-adjuvant treatment and the histological response after surgery in terms of metabolic criteria. | The purpose of this study is to determine predictive parameters for response to the first phase of treatment by accurately identifying the characteristics of tumors that have responded or not to chemotherapy and chemoradiotherapy. Metabolic criteria will be measured with the SUVmax values that will be determined on the 4 PET-MRI scans. | At the surgery | 
| Description of the correlation between the PET-MRI changes after neo-adjuvant treatment and the histological response after surgery in terms of MRI criteria. | MRI criteria will be measured with the Apparent Diffusion Coefficient (ADC) values that will be determined on the 4 PET-MRI scans. | At the surgery | 
| Description of the correlation between the PET-MRI changes after neo-adjuvant treatment and the histological response after surgery in terms of anatomopathological criteria. | Anatomopathological criteria will be measured with the histopathological response to treatment which will be defined according to the tumor regression grade (TRG) | At the surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the first PET-MRI staging with standard of care imaging, namely pelvic MRI in terms of tumor volumes | Record of tumor volumes on MRI PET 1 | At the PET MRI pretherapy (= PET MRI 1) | 
| Comparison of the first PET-MRI staging with standard of care imaging, namely pelvic MRI in terms of SUVmax values | Record of SUVmax on MRI PET 1 | At the PET MRI pretherapy (= PET MRI 1) | 
| Comparison of the first PET-MRI staging with standard of care imaging, namely pelvic MRI in terms of ADC values | Record of ADC on MRI PET 1 | At the PET MRI pretherapy (= PET MRI 1) | 
| Description of the specific PET-MRI responses at mid-treatment of the neoadjuvant chemotherapy in terms of delta tumor volume | Record of delta tumor volume, compared to baseline (PET MRI 1) | At the 2nd PET (PET2), up to 28 months | 
| Description of the specific PET-MRI responses at mid-treatment of the neoadjuvant chemotherapy in terms of delta SUVmax values | Record of delta SUVmax, compared to baseline (PET MRI 1) | At the 2nd PET (PET2), up to 28 months | 
| Description of the specific PET-MRI responses at mid-treatment of the neoadjuvant chemotherapy in terms of delta ADC values | Record of delta ADC, compared to baseline (PET MRI 1) | At the 2nd PET (PET2), up to 28 months | 
| Description of the specific PET-MRI responses to neoadjuvant chemotherapy in terms of delta tumor volume | Record of delta tumor volume, compared to baseline (PET MRI 1) | At the 3rd PET (PET3), up to 28 months | 
| Description of the specific PET-MRI responses to neoadjuvant chemotherapy in terms of delta SUVmax values | Record of delta SUVmax, compared to baseline (PET MRI 1) | At the 3rd PET (PET3), up to 28 months | 
| Description of the specific PET-MRI responses to neoadjuvant chemotherapy in terms of delta ADC values | Record of delta ADC, compared to baseline (PET MRI 1) | At the 3rd PET (PET3), up to 28 months | 
| Description of the specific PET-MRI responses to neoadjuvant radiochemotherapy in terms of delta tumor volume | Record of delta tumor volume, compared to PET3 | At the 4th PET (PET4), up to 28 months | 
| Description of the specific PET-MRI responses to neoadjuvant radiochemotherapy in terms of delta SUVmax values | Record of delta SUVmax, compared to PET3 | At the 4th PET (PET4), up to 28 months | 
| Description of the specific PET-MRI responses to neoadjuvant radiochemotherapy in terms of delta ADC values | Record of delta ADC, compared to PET3 | At the 4th PET (PET4), up to 28 months | 
| Propose standardized criteria to differentiate responders from non-responders | Record of clinical and iconographic data predictive of good response to treatment | Data record throughout the study, up to 28 months |