Rectal Cancer
Conditions
Keywords
64Cu-ATSM, neoadjuvant treatment, chemoradiotherapy, surgery, Positron Emission Tomography (PET)/CT scan, Prediction of response to treatment, Rodel score
Brief summary
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
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.
Interventions
DRUG64Cu-ATSM
64 Cu-ATSM PET/CT scan
Sponsors
Fondation ARC
Institut Cancerologie de l'Ouest
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Multicentric, open prospective study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relationship between early tumor uptake of 64Cu-ATSM PET/CT images and prediction of histological response to neo-adjuvant chemo-radiotherapy treatment | 4 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between 64Cu-ATSM uptake and oxidative stress markers | 4 months | 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 |
| Progression free survival | 2 years | Progression Free survival is the delay between surgery and the date of documented disease progression |
| Relationship between late tumor uptake of 64Cu-ATSM PET/CT images and prediction of histological response to neo-adjuvant chemo-radiotherapy treatment | 4 months | 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) |
| Comparison between early and late 64Cu-ATSM uptakes in 64Cu-ATSM PET/CT images | 45 days | Early and Late tumor uptake of 64Cu-ATSM will be assessed by SUV (Standardized Uptake Value) measurement |
| 64Cu-ATSM toxicity | 45 days | 64Cu-ATSM toxicity will be assessed by vital signs monitoring within 2 hours after 64Cu-ATSM injection |
| 18FDG-PET/CT and 64Cu-PET/CT uptakes | 45 days | Correlation between 18FDG-PET/CT and 64Cu-PET/CT uptakes |
Countries
France
Outcome results
None listed