Study on the association of radiotherapy with capecitabine and temozolomide followed by surgery in patients with locally advanced rectal cancer

Phase 1

• Conditions: ocaly advanced low-risk rectal cancer, placed at less then 15 cm form the anal verge and staged as cT = 2 and cN0 or cT1-3 cN1 (TNM classification 8th edition), without evidence of distant metastases (cM0).The study requires central confirmation of tumor molecular status of microsatellitestability by multiplex polymerase chain reaction, lack of MGMT expression by immunohistochemistry (IHC) and evidence of MGMT promoter methylation by pyrosequencing.; MedDRA version: 20.0Level: HLTClassification code 10010023Term: Colorectal neoplasms malignantSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-002325-18-IT
• Lead Sponsor: FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-07-27
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

-Written informed consent to study procedures;
-Age = 18 years;
-ECOG PS 0-1;
-Life expectancy of at least 5 years (excluding diagnosis of cancer);
-Histologically confirmed diagnosis of rectal adenocarcinoma, with centrally confirmed mismatch repair proficiency by multiplex polymerase chain reaction (PCR), lack of MGMT expression by immunohistochemistry and MGMT promoter methylation by pyrosequencing;
-Locally advanced, resectable disease defined by the presence of at least one of the following features:
oDistal tumor margin at <15 cm from the anal verge;
ocT3N0 or cT1-3N1(with the definition of a clinically positive lymph node being any node = 1 cm);
oLess than four lymph nodes in the mesorectum showing morphological signs on MRI indicating metastatic disease;
oNo evidence of enlarged lateral pelvic clinically positive lymph node (> 1 cm);
oNo evidence of extramural vascular invasion (EMVI);
oNo evidence of metastatic disease by CT scan of the chest and abdomen and total body FDG PET/CT scan;
oNo clear indication of involvement of the pelvic side walls by imaging;
-Tumor must be amenable to curative resection (curative resection can include pelvic exenteration);
-Hematopoietic: absolute neutrophil count =1500/mm3; platelet count = 100,000/mm3; haemoglobin level = 10 g/dL;
-Hepatic total bilirubin =1.5 time upper limit of normal (ULN); alkaline phosphatase = 2 times ULN; AST and ALT = 2.5 times ULN Serum creatinine = 1.5 × ULN or renal creatinine clearance = 50 mL/min according to the Cockcroft-Gault formula (or local institutional standard methods).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 21
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

-Dihydropyrimidine dehydrogenase (DPD) deficiency;
-Previous pelvic RT;
-Any of the following in the 6 months prior to treatment start: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure (= New York Heart Association Classification Class II), cerebrovascular accident/stroke, transient ischemic attack, serious cardiac arrhythmia requiring medication or symptomatic pulmonary embolism;
-Uncontrolled coagulopathy;
-Active infection requiring systemic therapy;
-Infection with human immunodeficiency virus (HIV) plus CD4 cells <200/mm3 or AIDS-defining conditions despite HAART;
-Lack of upper gastrointestinal tract integrity or malabsorption syndrome; immune colitis; active inflammatory bowel disease (i.e., patients requiring current medical interventions or who are symptomatic);
-Patients with prior malignancies (with the exception of rectal cancer), including invasive colon cancer, are eligible provided they have been disease-free for = 3 years and are deemed by their physician to be at low risk for recurrence (patients with effectively treated squamous cell or basal cell skin cancer, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum are eligible even if diagnosed less than 3 years before study enrollment);
-Other severe acute or chronic medical conditions including immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study;
-Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies;
-Pregnant or lactating women.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified