64Cu-ATSM PET/CT in Rectum Cancer (TEP 64Cu-ATSM-Rectum)

Study Overview
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Brief Summary
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This phase II trial is assessing how 64Cu-ATSM (64Cu-copper(II) diacetylbis(N4-methylthiosemicarbazone)) PET/CT scan could predict neo adjuvant treatment response in rectum cancer locally advanced

Detailed Description
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The purpose of this study is to evaluate early and late tumor uptake of 64Cu-ATSM in predicting histological response to neo-adjuvant chemo-radiotherapy treatment in patients with locally advanced rectal cancer. Patients receive pre-therapeutic CT scan, Pelvic MRI and 18FDG (fluorodeoxyglucose) PET/CT (positron emission tomography) scan within 45 days before enrollment. 64Cu-ATSM PET/CT scan is done before chemoradiotherapy treatment start. About 3 MBq/Kg of 64Cu-ATSM are injected intravenously, two acquisition sequences are performed 1 hour and 23 to 25 hours after injection in order to evaluate early and late tumor uptake of 64Cu-ATSM. Patients are treated for 5 weeks by Capecitabine chemotherapy (1600 mg/m2/day) combined to 50 Gy radiotherapy. Pelvic MRI is performed 4 weeks after chemotherapy in order to evaluate the treatment efficacy. Surgery is scheduled 6 to 8 weeks after chemoradiotherapy. Tissue samples from previously collected rectal biopsy (obtained for diagnosis) and from surgery are used for assessing oxidative stress markers by Immuno-histochemical analysis. Chest, abdomen and pelvis CT scan is performed every 6 months after surgery in order to assess progression free survival.

Official Title
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Evaluation of 64Cu-ATSM PET/CT in Predicting Neo Adjuvant Treatment Response in Locally Advanced Rectum Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: 64Cu-ATSM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed rectum adenocarcinoma Locally advanced, non metastatic disease, with or without locoregional lymph node involvement (greater than or equal to T3 +/- N), first-line therapy 18 Years and older Performance Status equal to 0 or 1 Fertile patients must use effective contraception Hemoglobin greater than 9g/dl, neutrophils greater than 1 500/mm3, platelets greater than 100 000/mm3 Creatinine clearance greater than or equal to 50ml/min Plan to receive treatment with concurrent chemotherapy and radiation therapy followed by surgery Totality of the tumor included in the radiotherapy field Written informed consent Patient must be affiliated to a Social Health Insurance Exclusion Criteria: metastatic disease Patient contraindicated for capecitabine or 5FU (5-Fluoro-Uracile) derivatives (history of severe and unexpected reactions to fluoropyrimidine-containing therapy, known hypersensitivity to 5FU, to any of the excipients, or known total DPD (dihydropyrimidine déshydrogénase) deficiency) Known Contraindication to perform MRI Previous treatment with pelvic radiotherapy Chronic inflammatory bowel disease, malabsorption, lack of colonic integrity Diarrhea grade greater than 2 Contraindication to surgery Bilateral total hip prosthesis Other malignancy treated within the last 5 years (except non-melanoma skin cancer or in situ carcinoma of the cervix) Pregnant or nursing patient Individual deprived of liberty or placed under the authority of a tutor Impossibility to submit to the medical follow-up of this clinical trial for geographical, social or psychological reasons Agitation; impossibility of lying motionless for at least 1 hour, or known claustrophobia

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Multicentric, open prospective study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 64Cu ATSM<br>pretherapeutic 64Cu-ATSM PET/CT scan | Drug: 64Cu-ATSM<br>* 64 Cu-ATSM PET/CT scan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between early tumor uptake of 64Cu-ATSM PET/CT images and prediction of histological response to neo-adjuvant chemo-radiotherapy treatment | Early tumor uptake of 64Cu-ATSM will be assessed by SUV (Standardized Uptake Value) measurement, histological response Will be assessed by Rodel grading (Tumor Regression Grading) | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between late tumor uptake of 64Cu-ATSM PET/CT images and prediction of histological response to neo-adjuvant chemo-radiotherapy treatment | Late tumor uptake of 64Cu-ATSM will be assessed by SUV (Standardized Uptake Value) measurement, histological response Will be assessed by Rodel grading (Tumor Regression Grading) | 4 months | 
| Correlation between 64Cu-ATSM uptake and oxidative stress markers | Aggressive zones corresponding to high redox potential areas will be assessed by Immuno-histochemical analysis on the surgical sample and on the pre-therapeutic biopsy | 4 months | 
| Progression free survival | Progression Free survival is the delay between surgery and the date of documented disease progression | 2 years | 
| 18FDG-PET/CT and 64Cu-PET/CT uptakes | Correlation between 18FDG-PET/CT and 64Cu-PET/CT uptakes | 45 days | 
| Comparison between early and late 64Cu-ATSM uptakes in 64Cu-ATSM PET/CT images | Early and Late tumor uptake of 64Cu-ATSM will be assessed by SUV (Standardized Uptake Value) measurement | 45 days | 
| 64Cu-ATSM toxicity | 64Cu-ATSM toxicity will be assessed by vital signs monitoring within 2 hours after 64Cu-ATSM injection | 45 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rodel score, 64Cu-ATSM, neoadjuvant treatment, chemoradiotherapy, surgery, Positron Emission Tomography (PET)/CT scan, Prediction of response to treatment