Clinical trial NCT03951337: 64Cu-ATSM PET/CT in Rectum Cancer (TEP 64Cu-ATSM-Rectum)
Official title: Evaluation of 64Cu-ATSM PET/CT in Predicting Neo Adjuvant Treatment Response in Locally Advanced Rectum Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: 64Cu-ATSM
neoadjuvant treatment
chemoradiotherapy
surgery
Positron Emission Tomography (PET)/CT scan
Prediction of response to treatment
Rodel score
Lead sponsor: Institut Cancerologie de l'Ouest
Sponsor class: OTHER
Collaborators: name: Fondation ARC
First posted: 2019-05-15
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Multicentric, open prospective study
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Relationship between early tumor uptake of 64Cu-ATSM PET/CT images and prediction of histological response to neo-adjuvant chemo-radiotherapy treatment
timeFrame: 4 months
Secondary outcomes:
measure: Relationship between late tumor uptake of 64Cu-ATSM PET/CT images and prediction of histological response to neo-adjuvant chemo-radiotherapy treatment
timeFrame: 4 months
measure: Correlation between 64Cu-ATSM uptake and oxidative stress markers
timeFrame: 4 months
measure: Progression free survival
timeFrame: 2 years
measure: 18FDG-PET/CT and 64Cu-PET/CT uptakes
timeFrame: 45 days
measure: Comparison between early and late 64Cu-ATSM uptakes in 64Cu-ATSM PET/CT images
timeFrame: 45 days
measure: 64Cu-ATSM toxicity
timeFrame: 45 days
Other outcomes:
Locations:
city: Angers
country: France
facility: Institut de Cancerologie de l'Ouest (ICO)
city: Brest
country: France
facility: CHU de BREST
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Herblain
country: France
facility: Institut de cancerologie de l'Ouest
Study officials:
affiliation: Institut de Cancerologie de l'Ouest
name: Mathilde COLOMBIE, MD
role: PRINCIPAL_INVESTIGATOR
References: