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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: 64Cu-ATSM

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 Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers, France, 49055
    • Institut de Cancérologie de l'Ouest (ICO)
  • Brest, France, 29200
    • CHU de Brest
  • Rennes, France, 35045
    • Centre Eugène Marquis
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint Herblain, France, 44805
    • Institut de Cancérologie de l'Ouest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 64Cu ATSM; pretherapeutic 64Cu-ATSM PET/CT scan	Drug: 64Cu-ATSM; 64 Cu-ATSM PET/CT scan

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Institut Cancerologie de l'Ouest
• Collaborators: Fondation ARC
• Investigators: Principal Investigator: Mathilde COLOMBIE, MD, Institut de Cancérologie de l'Ouest

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2019
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: April 26, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (Actual): May 15, 2019

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: surgery; neoadjuvant treatment; chemoradiotherapy; 64Cu-ATSM; Positron Emission Tomography (PET)/CT scan; Prediction of response to treatment; Rodel score
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: ICO-N-2017-14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No