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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS Istituto Nazionale Dei Tumori

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Dec 2021 → ongoing

Decision date (initial)

2024-08-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513931-26-00

EudraCT number

2021-002325-18

ClinicalTrials.gov

NCT05136326

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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.

Secondary objectives 1

1. To assess the activity of the addition of temozolomide to the standard concurrent capecitabine-based chemoradiation in terms of R0 resection rate, downstaging rate and sphincter preservation rate in patients with low-risk locally advance rectal cancer molecularly selected formicrosetellite stability, MGMT negative IHC and MGMT promoter methylation. To estimate the local recurrence rate (defined as the rate of detectable local disease at follow-up after study treatment completion), the progression-free survival and overall survival of this treatment strategy and to further evaluate the safety profile of the combination of temozolomide with capecitabine as radiosensitizing agents in neoadjuvant treatment for locally advanced rectal cancer.

Conditions and MedDRA coding

locally advanced rectal cancer (LARC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Written informed consent to study procedures
2. Age = 18 years
3. ECOG PS 0-1
4. Life expectancy of at least 5 years (excluding diagnosis of cancer)
5. 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
6. Locally advanced, resectable disease defined by the presence of at least one of the following features
7. Distal tumor margin at <15 cm from the anal verge
8. cT3N0 or cT1-3N1(with the definition of a clinically positive lymph node being any node = 1 cm)
9. Less than four lymph nodes in the mesorectum showing morphological signs on MRI indicating metastatic disease
10. No evidence of enlarged lateral pelvic clinically positive lymph node (> 1 cm)
11. No evidence of extramural vascular invasion (EMVI)
12. No evidence of metastatic disease by CT scan of the chest and abdomen and total body FDG PET/CT scan
13. No clear indication of involvement of the pelvic side walls by imagin
14. Tumor must be amenable to curative resection (curative resection can include pelvic exenteration)
15. No prior infiltrating tumors of the rectum
16. Hematopoietic: absolute neutrophil count =1500/mm3; platelet count = 100,000/mm3; haemoglobin level = 10 g/dL
17. 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)

Exclusion criteria 11

1. Dihydropyrimidine dehydrogenase (DPD) deficiency
2. Previous pelvic RT
3. 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
4. Uncontrolled coagulopathy
5. Active infection requiring systemic therapy
6. Infection with human immunodeficiency virus (HIV) plus CD4 cells <200/mm3 or AIDSdefining conditions despite HAART
7. 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)
8. 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)
9. 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
10. Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies
11. Pregnant or lactating women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pathologic complete response (pCR), defined as complete histological regression with no available tumor cells (yT0N0) in the intention-to-treat population

Secondary endpoints 6

1. R0 resection rate (defined as the rate of microscopically margin-negative resections)
2. 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)
3. Sphincter preservation rate (defined as the percentage of patients with preserved anorectal sphincter after surgery)
4. Local recurrence rate (defined as the rate of detectable local disease at follow-up after study treatment completion)
5. disease-free survival
6. overall survival

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Istituto Nazionale Dei Tumori

Sponsor organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Address

Via Giacomo Venezian 1

City

Milan

Postcode

20133

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Filippo Pietrantonio

Public contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Ufficio Relazioni con il pubblico

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications