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

ABSTRACT: Primary objectives: The main objective of the trial is to evaluate the activity, in terms of pathologic complete response, of the addition of temozolomide to standard concurrent capecitabine-based chemoradiation, in moleculary selected patient with low-risk locally advance rectal cancer molecularly selected formicrosetellite stability, MGMT negative IHC and MGMT promoter methylation. Primary endpoints: Pathologic complete response (pCR), defined as complete histological regression with no available tumor cells (yT0N0) in the intention-to-treat population.

DISEASE(S): Adenocarcinoma Del Retto Localmente Avanzato A Basso Rischio, Stadiato Clinicamente, Secondo La Classificazione Tnm (8° Edizione) Come Ct=2 Ed N0 Oppure Ogni Ct1-3 Cn1, Senza Evidenza Di Metastasi A Distanza (cm0) E Localizzato A Meno Di 15 Cm Dallo Sfintere Anale Esterno. Presenza Di Stabilità Microsatellitare, Negatività Di Espressione Immunoistochimica Di Mgmt Sul Materiale Istologico Ed Evidenza Di Metilazione Del Promotore Del Gene Mgmt In Pirosequenziamento.,Localy 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.,Colorectal Neoplasms Malignant

PROVIDER: 2541423 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Surgical resection is curative for 75% of stage II and 50% of stage III colon cancer patients. The magnitude of benefit of adjuvant chemotherapy in terms of disease-free (DFS) and overall survival (OS) varies according to TNM stage and microsatellite status. Standard adjuvant chemotherapy includes fluoropyrimidine and oxaliplatin regimens for up to six months. Circulating tumor DNA (ctDNA) detected after surgical resection reflects the presence of micrometastatic disease and pivotal observational studies addressed the prognostic value of ctDNA in the post-surgical setting. Adjuvant chemotherapy can promote the clearance of ctDNA, and ctDNA clearance after adjuvant chemotherapy is prognostic for better DFS in patients with stage III resected cancers and post-operative positive ctDNA. ctDNA may be investigated as a potential real-time surrogate biomarker of the efficacy of adjuvant therapy, but suggest that patients with ctDNA persistence after standard chemotherapy might be "molecularly metastatic" and may benefit from additional "consolidation" non-cross resistant strategies aimed at clearing micrometastatic disease. Temozolomide has modest but non-negligible activity (about 10%) in chemo-refractory patients with MGMT methylated mCRC. The response rate to temozolomide-based therapy in pretreated patients is increased to up to 20% when restricting the focus on those with MGMT IHC-negative/MGMT methylated and MSS cancers Significant activity (ORR 26%) and favorable safety profile were reported by the combination of temozolomide and irinotecan (TEMIRI regimen) in patients with pretreated MGMT methylated/MSS mCRC, thus suggesting that the two agents may have synergist activity in line with preclinical data. Based on all these considerations, there is a strong rationale for investigating TEMIRI regimen as consolidation non-cross resistant therapy in a liquid-biopsy driven interventional trial. Eligible patients with MGMT-silenced, MSS, radically resected CRC and detectable ctDNA after standard chemotherapy will be enrolled and will receive 6-month post-adjuvant/consolidation TEMIRI (given for up to 6 monthly cycles).

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

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