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

Phase 2

Active, not recruiting

• Conditions: Rectal Cancer
• Interventions: Drug: 64Cu-ATSM

• Registration Number: NCT03951337
• Lead Sponsor: Institut Cancerologie de l'Ouest

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.

Study Timeline

• Study Start: 2019-04-26
• Study First Submitted: 2019-04-26
• Study First Submitted QC: 2019-05-14
• Study First Posted: 2019-05-15
• Status Verified: 2024-02
• Last Update Submitted: 2024-03-11
• Last Update Posted: 2024-03-12
• Primary Completion: 2024-07
• Study Completion: 2026-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 70

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
64Cu ATSM	64Cu-ATSM	pretherapeutic 64Cu-ATSM PET/CT scan

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
64Cu-ATSM toxicity	45 days	64Cu-ATSM toxicity will be assessed by vital signs monitoring within 2 hours after 64Cu-ATSM injection
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)
Progression free survival	2 years	Progression Free survival is the delay between surgery and the date of documented disease progression
18FDG-PET/CT and 64Cu-PET/CT uptakes	45 days	Correlation between 18FDG-PET/CT and 64Cu-PET/CT uptakes
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
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

Trial Locations

Locations (5)

Institut de Cancerologie de l'Ouest (ICO); 🇫🇷 Angers, France

Centre Eugene Marquis; 🇫🇷 Rennes, France

Institut de cancerologie de l'Ouest; 🇫🇷 Saint Herblain, France

CHU de BREST; 🇫🇷 Brest, France

Centre Henri Becquerel; 🇫🇷 Rouen, France