BridgeMD
New treatment option for Colorectal Cancer
Official title Pre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN)
ClinicalTrials.gov ID: NCT05845450
What this study is testing
What is Trastuzumab deruxtecan?
Trastuzumab deruxtecan is an investigational medicine, given as an once-daily injection under the skin, being studied as a potential treatment for colorectal cancer.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This is a window-of-opportunity umbrella platform trial enrolling non-metastatic resectable colorectal patients selected for the presence of a specific targetable molecular alteration. The study aims to test the activity of specific targeted agents/combinations given as a short-course pre-operative strategy, matched with the specific alteration detected, followed by standard of care surgery.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- General Provide a signed and dated informed consent document.
- Age ≥ 18 years at time of informed consent.
- ECOG PS of 0 and 1.
- Histologically confirmed colorectal cancer adenocarcinoma that is judged as initially resectable with elective surgery aimed at radical intent with...
- Radiological stage cT3-4, N0-2, M0 using computed tomography (CT) as in the pivotal FOxTROT study.
You likely can't join if
- General exclusion criteria
- Distant metastases at any site, as defined by negativity of chest/abdomen/pelvis contrast-enhanced computed tomography (CT).
- Risk criteria for obstructing disease at radiology or endoscopy as defined in the pivotal FOxTROT study.
- 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.
See the full eligibility criteria
Who can join
- General Provide a signed and dated informed consent document.
- Age ≥ 18 years at time of informed consent.
- ECOG PS of 0 and 1.
- Histologically confirmed colorectal cancer 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.
- 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)...
- ≤ T3a defined at the MRI (perivisceral fat infiltration \<2 mm) and clinical N0
- Upper-medium, defined as tumors with distal margin ≥ 5 cm from the anal verge.
- Absence of mesorectal fascia invasion, as defined as a distance ≥ 1 mm between tumor and the mesorectal fascia.
- 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 (absolute neutrophil count ≥ 1.5 × 109/L; platelet count ≥ 100 × 109/L; hemoglobin ≥ 9.0 g/dL)
- 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 (serum total bilirubin ≤ 1.5 × ULN and \< 2 mg/dL. Note: Patients who have a total bilirubin level 1.5 × ULN will be allowed if their indirect bilirubin level is ≤ 1.5 × ULN; Alanine...
- Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for...
- people and their partners must be willing to avoid pregnancy during the trial and until a specific time interval after the last trial treatment: 7 months for female and 4 for male patients after last dose of...
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. Specific for each Cohort COHORT 1: pMMR/MSS status and HER2-positive status and LVEF ≥ 50% within 28 days...
What rules you out
- General exclusion criteria
- Distant metastases at any site, as defined by negativity of chest/abdomen/pelvis contrast-enhanced computed tomography (CT).
- Risk criteria for obstructing disease at radiology or endoscopy as defined in the pivotal FOxTROT study.
- 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...
- Known history of HIV infection.
- Active infection including tuberculosis, hepatitis B, 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...
- 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...
- 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 drugs. Specific exclusion criteria for each Cohort: COHORT 1:
- Previous treatment with a DXd-containing ADC or any anti-HER2 agent.
- Has LVEF\< 50% within 28 days before enrolment.
- Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening. (eg, pulmonary emboli within 3...
- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the enrolment, severe asthma, severe chronic...
- Any autoimmune, connective tissue, or inflammatory disorders where there is documented, or a suspicion of, pulmonary involvement at the time of Screening.
- Prior pneumonectomy.
- Has substance abuse or any other medical conditions that may interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
- Patients with a medical history of myocardial infarction within 6 months before randomization/enrolment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), people with troponin...
- Corrected QT interval (QTcF) prolongation to \> 470 msec (females) or \>450 msec (males) based on average of the screening triplicate12-lead ECG.
- A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). COHORT 2, 4, 5, 6, 7, 10 and Cohort 1 of UNICORN part 2:
- History of autoimmune diseases or history of bone marrow or organ transplantation that requires immunosuppressive therapy.
- History of active primary immunodeficiency.
- Any condition requiring systemic treatment with corticosteroids at doses equal or superior to 10 mg daily of prednisone or equivalents, or other immunosuppressive drugs within 14 days from the inclusion in the study.
- Administration of live vaccines within 4 weeks from the inclusion in the study. Note: patients, if enrolled, should not receive live vaccine while receiving study drug(s) and up to 30 days after the last dose of study...
- Prior treatment with anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents. COHORT 3 and 8
- History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan.
- Magnesium below the LNL.
- Prior treatment with an EGFR inhibitor. COHORT 8:
- Patients who are unable to take a drug by mouth or previous clinical conditions or surgical resection that may affect the absorption of the study drug.
- Use of CYP3A4 or P-gp substrates with a narrow therapeutic window within 14 days or 5 half-lives of the drug or its major active metabolite, whichever is longer.
- Use of any herbal medications/supplements.
- Tumors with KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations, except KRAS G12C.
- Prior treatment with a KRAS G12C inhibitor. COHORT 9 and 10:
- Prior treatment with EP4 receptor antagonists.
- Inability to swallow medications.
- Presence of portal hypertension and/or oesophageal varices.
- Known severe gastritis, duodenal or gastric ulcer, or any other condition that may lead to bleeding or perforation. COHORTS 11 and 12:
- Prior treatment with an anti-EGFR and/or MET inhibitor.
- History of interstitial lung disease (e.g. pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan
- Clinically active infectious liver disease
- Any ophthalmologic condition that is clinically unstable
The study team makes the final eligibility decision.
Where it's taking place
- Milan, Lombardia/MI, Italy
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Milan, Lombardia/MI, Italy. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.