Preoperative Chemoradiotherapy With CApecitabine and Temozolomide in MGMT Silenced, MSS, Locally Advanced RecTal Cancer (CATARTIC)
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|ClinicalTrials.gov Identifier: NCT05136326|
Recruitment Status : Recruiting
First Posted : November 29, 2021
Last Update Posted : February 8, 2022
In patients with locally advanced rectal cancer (LARC), preoperative chemo-radiotherapy (CTRT) is considered the standard of care. Preoperative CTRT approach often results in a significant tumor downstaging and local control, with evidence of complete pathological response (pCR) rate of about 15% in high volume institutions. In high-risk LARC a new strategy called total neoadjuvant therapy (TNT) has emerged, in which systemic chemotherapy with fluorouracil and oxaliplatin (RAPIDO trial) or with the triplet FOLFIRINOX (as was used in the PRODIGE 23 study) is incorporated before or after the administration of short-course RT or neoadjuvant CTRT and prior to surgery. However, given the fact that TNT may represent an overtreatment for a subset of patients, additional therapeutic strategies are warranted to improve the outcomes also in patients with lower risk that are not good candidate for a TNT.
In the era of personalized medicine, tumor molecular profiling may lead to the identification of therapeutic targets for pharmacological intervention potentially useful to enhance treatment outcomes.
O(6)-methylguanine-DNA-methyltransferase (MGMT) repairs DNA damage induced by alkylating agents and MGMT inactivation due to promoter methylation confers enhanced sensitivity to alkylating agents such as temozolomide (TMZ).
TMZ has modest activity in patients with MGMT-methylated pretreated metastatic colorectal cancer and responses are restricted to tumors with complete MGMT loss by immunohistochemistry (IHC) and microsatellite stable (MSS) status.
Both capecitabine and temozolomide induces deoxythymidine triphosphate thymidine pool depletion might induce deoxyribonucleic acid (DNA)-double strand breaks and eventually apoptosis in rapidly dividing cells. On the basis of such evidences, there is a strong biological and clinical rationale for testing the addition of TMZ to capecitabine-based CTRT in patients with MGMT silenced and MSS technically resectable LARC.
The aim of this trial is investigating whether the addition of TMZ to standard concurrent capecitabine-based long-course chemoradiation may increase pCR rate as compared to historical control in patients with locally advanced rectal cancer not candidate to TNT and molecularly selected for the presence of MGMT silencing and microsatellite stable status.
|Condition or disease||Intervention/treatment||Phase|
|Rectal Cancer||Radiation: External-beam radiation Drug: Capecitabine Drug: Temozolomide||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Phase II, multicentre, non-randomized, open-label trial|
|Masking:||None (Open Label)|
|Official Title:||Multicenter Phase II Study of Preoperative Chemoradiotherapy With CApecitabine Plus Temozolomide in Patients With MGMT Silenced and Microsatellite Stable Locally Advanced RecTal Cancer: the CATARTIC Trial|
|Actual Study Start Date :||December 1, 2021|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2026|
Experimental: Catartic: chemoradiotherapy plus temozolomide
External-beam radiation: 50.4 GY (45 Gy in 25 fractions + Boost 5.4 Gy in 3 fractions over 5 weeks) in association with:
Capecitabine 825 mg/sqm/bid per os (p.o.) 5 days/week for 5 weeks plus Temozolomide 75 mg/sqm p.o. 5 days/week for 5 weeks.
Radiation: External-beam radiation
External-beam radiation 50.4 GY (45 Gy in 25 fractions + Boost 5.4 Gy in 3 fractions over 5 weeks)
825 mg/sqm/bid per os (p.o.) 5 days/week for 5 weeks;
75 mg/sqm p.o. 5 days/week for 5 weeks
- To evaluate the rate of complete pathologic response (pCR) [ Time Frame: 24 months ]pCR, defined as complete histological regression with no available tumor cells yT0N0
- To assess the R0 resection rate [ Time Frame: 24 months ]R0 defined as the rate of microscopically margin-negative resections
- To assess the tumor downstaging rate [ Time Frame: 24 months ]Tumor downstaging rate defined as the rate of reduction in the stage of the tumor as a result of pre-operative therapy, from a more to a less threatening stage at the radiologic assessment after the the end of CTRT
- To assess the rate of sphincter preservation [ Time Frame: 24 months ]Sphincter preservation rate defined as the percentage of patients with preserved ano-rectal sphincter after surgery
- To assess the rate of local recurrence rate [ Time Frame: 24 months ]Local recurrence rate defined as the rate of detectable local disease at follow-up after study treatment completion
- To assess the disease-free survival [ Time Frame: The disease-free survival will be evaluated during a follow up of 5 years ]Disease-free survival defined as the time from the enrollment in the study to the occurrence of disease relapse (local and/or distant) or death from any cause
- To assess the overall survival [ Time Frame: The overall survival will be evaluated during a follow up of 5 years ]Overall survival defined as the time from the enrollment in the study to the occurrence of death.
- To assess the incidence, nature, and severity of adverse events [ Time Frame: 24 months ]Adverse events defined and graded according to the NCI CTCAE v5.0
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05136326
|Contact: Filippo Pietrantonio, MD||+39 firstname.lastname@example.org|
|Contact: Federica Morano, MD||+39 email@example.com|