Window-of-opportunity umbrella platform trial of short-course pre-operative targeted treatments in patients with molecularly selected and resectable primary colorectal cancer: the UNICORN study.

Trial details

Who runs it

Fondazione GONO G.I.

Trial code

EU 2022-501308-90-00

Record updated

2026. június 3.

Original description

To assess the activity of each specific short-course preoperative targeted treatment as measured in terms of pathological complete response (pCR) plus major response (pMR) rate in each cohort. For patients enrolled in cohorts 11 and 12, a co-primary endpoint consists in timely surgery, which is defined as the performance of planned surgery with a delay of no more than 14 days beyond the pre-specified 35 days after treatment start owing to treatment-related adverse events.Read full original descriptionShow less

WINDOW-OF-OPPORTUNITY UMBRELLA PLATFORM TRIAL OF SHORT-COURSE PRE-OPERATIVE OR NEOADJUVANT TARGETED TREATMENT IN PATIENTS WITH MOLECULARLY SELECTED AND RESECTABLE PRIMARY COLORECTAL CANCER: THE UNICORN STUDY

To assess the activity of each specific short-course preoperative targeted treatment as measured in terms of pathological complete response (pCR) plus major response (pMR) rate in each cohort. For patients enrolled in cohorts 11 and 12, a co-primary endpoint consists in timely surgery, which is defined as the performance of planned surgery with a delay of no more than 14 days beyond the pre-specified 35 days after treatment start owing to treatment-related adverse events.

Inclusion: General inclusion criteria for the study population. • Provide a signed and dated informed consent document prior to any study procedure. • Age ≥ 18 years at time of informed consent. • ECOG PS of 0 or 1. • Histologically confirmed colorectal adenocarcinoma that is judged as initially resectable with elective surgery aimed at radical intent with R0 margins as per multidisciplinary team assessment. • Radiological stage cT3-4, N0-2, M0 using computed tomography (CT) as in the pivotal FOxTROT study (see Section 5.1.1). • Patients with rectal cancer candidate for R0 resection, not requiring pre-operative radiotherapy based on multidisciplinary team assessment, with the following characteristics on high-resolution thin slice (3 mm) contrast-enhanced magnetic resonance imaging (MRI). • Absence of distant metastases at baseline as defined by negativity of chest/abdomen/pelvis contrast-enhanced computed tomography (CT). • Able to provide enough archival FFPE tumor specimen that is already available from initial diagnostic procedures for the purpose of molecular pre-screening. • Presence of one of the selected molecular profile/alteration after central pre-screening and necessary for the assignment to a matching treatment cohort. • No prior systemic treatment for colorectal cancer or neoadjuvant radiation therapy for rectal cancer. • Adequate bone marrow function characterized by the following at screening. • Adequate renal function characterized by serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 50 mL/min at screening. • Adequate hepatic function characterized by the following at screening. • Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. • Subjects and their partners must be willing to avoid pregnancy during the trial and until a specific time interval after the last trial treatment: 4 months after last dose of trastuzumab-deruxtecan, 3 months for durvalumab, botensilimab and balstilimab and 2 months for panitumumab alone or in combination with sotorasib. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the Investigator (barrier contraceptive measure or oral contraception). • Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion: General exclusion criteria for the study population Patients meeting any of the following criteria will be excluded from the study: • Distant metastases at any site. • Risk criteria for obstructing disease at radiology or endoscopy as defined in the pivotal FOxTROT study (see Section 5.1.1). • Need to receive neoadjuvant radiation or chemoradiation in patients with rectal cancer. • Patients with known hypersensitivity to the study drug of the assigned cohort or to its excipients or to drugs belonging to the same drug class. • Previous or concurrent malignancy within 2 years of study entry. • Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: history of acute myocardial infarction, acute coronary syndromes (including unstable angina, coronary artery bypass graft, coronary angioplasty or stenting) ≤ 6 months prior to start of study treatment; symptomatic congestive heart failure (i.e., Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality ≤ 6 months prior to start of study treatment, except atrial fibrillation and paroxysmal supraventricular tachycardia. • Known history of HIV infection. • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible only in case of negativity of HBV DNA. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. • Other severe acute or chronic diseases that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study. • Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with trial requirements. • Women in pregnancy or lactation condition. Women with child-bearing potential or sexually-active men not willing to use adequate contraception during whole study period. • Use of any disallowed drug, as explained in Section 9.2, that cannot be suspended ≤ 1 week before study treatment start.

EU CTIS 2022-501308-90-00