TEMOZOLOMIDE for Locally advanced rectal cancer

Inclusion criteria

• {"criterion_text":"- Written informed consent to study procedures"}
• {"criterion_text":"- No evidence of enlarged lateral pelvic clinically positive lymph node (> 1 cm)"}
• {"criterion_text":"- No evidence of extramural vascular invasion (EMVI)"}
• {"criterion_text":"- No evidence of metastatic disease by CT scan of the chest and abdomen and total body FDG PET/CT scan"}
• {"criterion_text":"- No clear indication of involvement of the pelvic side walls by imagin"}
• {"criterion_text":"- Tumor must be amenable to curative resection (curative resection can include pelvic exenteration)"}
• {"criterion_text":"- No prior infiltrating tumors of the rectum"}
• {"criterion_text":"- Hematopoietic: absolute neutrophil count =1500/mm3; platelet count = 100,000/mm3; haemoglobin level = 10 g/dL"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Age = 18 years"}
• {"criterion_text":"- ECOG PS 0-1"}
• {"criterion_text":"- Life expectancy of at least 5 years (excluding diagnosis of cancer)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Locally advanced, resectable disease defined by the presence of at least one of the following features"}
• {"criterion_text":"- Distal tumor margin at <15 cm from the anal verge"}
• {"criterion_text":"- cT3N0 or cT1-3N1(with the definition of a clinically positive lymph node being any node = 1 cm)"}
• {"criterion_text":"- Less than four lymph nodes in the mesorectum showing morphological signs on MRI indicating metastatic disease"}

Exclusion criteria

• {"criterion_text":"- Dihydropyrimidine dehydrogenase (DPD) deficiency"}
• {"criterion_text":"- Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies"}
• {"criterion_text":"- Pregnant or lactating women"}
• {"criterion_text":"- Previous pelvic RT"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Uncontrolled coagulopathy"}
• {"criterion_text":"- Active infection requiring systemic therapy"}
• {"criterion_text":"- Infection with human immunodeficiency virus (HIV) plus CD4 cells <200/mm3 or AIDSdefining conditions despite HAART"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- Pathologic complete response (pCR), defined as complete histological regression with no available tumor cells (yT0N0) in the intention-to-treat population","definition_or_measurement_approach":"Defined as complete histological regression with no available tumor cells (ypT0N0) assessed on resected surgical specimen in the intention-to-treat population"}

Secondary endpoints

• {"endpoint_text":"- R0 resection rate (defined as the rate of microscopically margin-negative resections)","definition_or_measurement_approach":"Defined as the rate of microscopically margin-negative resections"}
• {"endpoint_text":"- Tumor downstaging rate (defined as the rate of reduction in the stage of the tumor as a result of therapy, from a more to a less threatening stage)","definition_or_measurement_approach":"Defined as the rate of reduction in tumor stage as a result of therapy (conversion from a more to a less advanced stage)"}
• {"endpoint_text":"- Sphincter preservation rate (defined as the percentage of patients with preserved anorectal sphincter after surgery)","definition_or_measurement_approach":"Defined as percentage of patients with preserved anorectal sphincter after surgery"}
• {"endpoint_text":"- Local recurrence rate (defined as the rate of detectable local disease at follow-up after study treatment completion)","definition_or_measurement_approach":"Defined as rate of detectable local disease at follow-up after study treatment completion"}
• {"endpoint_text":"- disease-free survival","definition_or_measurement_approach":"Time-to-event endpoint measuring time from index date (treatment) to recurrence or death (definition provided as 'disease-free survival')"}
• {"endpoint_text":"- overall survival","definition_or_measurement_approach":"Time-to-event endpoint measuring time from index date (treatment) to death from any cause (overall survival)"}

Italy

Earliest CTIS Part Ii Submission Date

19-06-2024

Latest Decision Or Authorization Date

05-08-2024

Processing Time Days

47

Number Of Sites

7

Number Of Participants

21

Primary sponsor

Full Name

Fondazione IRCCS Istituto Nazionale Dei Tumori

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy