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

Sponsor

Institut Cancerologie de l'Ouest (Other)

Overall Status

Recruiting

CT.gov ID

NCT03951337

Collaborator

Fondation ARC (Other)

Enrollment

Locations

Arm

47.2

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Drug: 64Cu-ATSM	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Multicentric, open prospective studyMulticentric, open prospective study

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Apr 26, 2019

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: 64Cu ATSM

pretherapeutic 64Cu-ATSM PET/CT scan

Drug: 64Cu-ATSM

64 Cu-ATSM PET/CT scan

Outcome Measures

Primary Outcome Measures

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

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)
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
18FDG-PET/CT and 64Cu-PET/CT uptakes [45 days]
Correlation between 18FDG-PET/CT and 64Cu-PET/CT uptakes
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Institut de Cancerologie de l'Ouest (ICO)	Angers	France	49055
2	CHU de BREST	Brest	France	29200
3	Centre Eugene Marquis	Rennes	France	35045
4	Centre Henri Becquerel	Rouen	France	76038
5	Institut de cancerologie de l'Ouest	Saint Herblain	France	44805