Upfront Trastuzumab-Deruxtecan Plus Capecitabine and Bevacizumab for Patients With HER-2 Positive Metastatic Colorectal Cancer.

Recruiting now · Phase 2

Conditions studied: Colorectal Cancer, Colorectal Adenocarcinoma, Rectal Adenocarcinoma, Rectal Cancer, Adenocarcinoma, Rectal Cancer, Metastatic, Colon Cancer Metastatic, Colon Cancer Adenocarcinoma

In brief

The aim of this study is to evaluate the activity of first-line trastuzumab-deruxtecan, capecitabine and bevacizumab in terms of overall response rate for patients with HER-2 positive metastatic/locally advanced unresectable colorectal cancer

Key facts

Study ID

NCT07407465

Run by

Gruppo Oncologico del Nord-Ovest

People needed

42

Starts

2025-10-20

Expected to finish

2027-10-20

Last updated by the study team

2026-02-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Written informed consent obtained from the patient/legal representative before performing any protocol-related procedures, including screening evaluations.
• Patient state to comply with all the study procedures and treatments. Patients must be accessible for treatment and follow-up. Patients registered for this trial must be treated and followed at the participating Centre.
• Age ≥ 18 years at the time of informed consent.
• ECOG Performance Status ≤ 2.
• Life expectancy of ≥ 3 months.
• Have histologically documented adenocarcinoma of the colon or rectum, which is initially metastatic or unresectable locally advanced.
• Subjects must be willing to provide the most recently available formalin-fixed paraffin-embedded tumor tissue blocks (or at least 25 freshly sectioned slides) for translational analyses (sampled before 1st treatment course). If archival tissue is not available for HER2 testing or for exploratory aims, then a newly obtained baseline biopsy of an accessible tumor lesion is required before Cycle 1 Day 1 timeframe. Biopsy must contain adequate tissue for analysis; the following biopsy types are acceptable: resection, excision, punch (skin lesions only) and core needle biopsies.
• Presence of locally determined HER2 overexpression/amplification defined as IHC 3+ or 2+/ISH amplified on archival/newly obtained tumor tissue, according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for gastric/gastroesophageal cancer.
• Have RAS known status and pMMR/MSS status by standard local testing.
• Have radiographically measurable disease per RECIST v1.1.
• Have adequate hematological, hepatic, renal, cardiac and coagulation function, as defined below, obtained ≤ 7 days prior to enrollment (Cycle 1 Day 1):
• Absolute neutrophil count (ANC) ≥ 1500/mm3. (Granulocyte-colony stimulating factor administration is not allowed within 1 week prior to C1D1).
• Platelet count ≥ 100000/mm3. (Platelet transfusion is not allowed within 1 week prior to C1D1)
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (≤ 5 x ULN if liver metastases are present).
• Serum albumin ≥ 2.5 g/dL.
• Creatinine clearance ≥ 60 mL/min as determined by Cockcroft-Gault (using actual body weight).
• Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before enrollment.
• International normalized ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 x ULN.
• Have had adequate washout period from previous treatment before screening, defined as:
• ≥ 4 weeks from major surgery.
• ≥ 4 weeks from radiation therapy, including palliative stereotactic radiation therapy to the chest.
• ≥ 3 weeks from anti-cancer chemotherapy [immunotherapy (non-antibody-based therapy)], retinoid therapy, hormonal therapy.
• ≥ 4 weeks from antibody-based anti-cancer therapy

You may not qualify if…

• Have previously received any systemic anticancer therapy for CRC in the metastatic/locally advanced unresectable setting or have participated in any interventional clinical trial for CRC in the metastatic/locally advanced unresectable setting. Subjects may have received prior fluoropyrimidine with or without oxaliplatin for CRC in the adjuvant or neoadjuvant setting if it was completed > 6 months before enrollment.
• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.
• Have previously been treated with an anti-HER2 agent and/or a topoisomerase I inhibitor.
• Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medications.
• Have substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, 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 (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Subjects with troponin levels above ULN at screening (as defined by the manufacturer) and without any myocardial-related symptoms should undergo a cardiologic consultation before enrollment to rule out MI.
• Corrected QT interval (QTcF) prolongation to > 470 msec (females) or > 450 msec (males) based on average of the screening 12-lead ECG.
• Symptomatic arterial hypertension or uncontrolled arterial hypertension, as determined by the investigator.
• Have a history of (non-infectious) ILD/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.).
• Any autoimmune, connective tissue, or inflammatory disorders (e.g., Rheumatoid arthritis, Sjögren's, sarcoidosis etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.
• Prior pneumonectomy (complete).
• A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
• Have unresolved toxicities from previous anticancer therapy, defined as toxicity (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to Grade > 2 for at least 3 months before enrollment/cycle 1 day 1 and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy such as: chemotherapy-induced neuropathy and fatigue.
• Patients with known hypersensitivity to the study drug or to its excipients.
• Patients with known hypersensitivity to other monoclonal antibodies.
• Pregnant or breastfeeding female patients, or patients who are planning to become pregnant. Sexually active men not willing to use adequate contraception during whole study period.
• Previous or concurrent malignancy within 3 years of study entry. Exceptions are adequately resected non-melanoma skin cancer, curatively treated in-situ diseases, and other solid tumors that have been curatively treated.
• Presence of any of the following dihydropyrimidine dehydrogenase (DPYD) polymorphism, based on local laboratory testing: DPYD 2a (c.1905+1G>A); DPYD13 (c.1679 T>G); DPYD D949V (c.2846 A>T). French and German patients may undergo baseline uracilemia assessment as detailed below in spite of polymorphism testing.
• Have a history of transient ischemic attack, cerebrovascular accident, myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery within 6 months prior to enrollment (Cycle 1 Day 1).
• Have a history of a significant bleeding event (e.g., bleeding needing medical intervention) within 6 months prior to enrollment (Cycle 1 Day 1) unless the source of bleeding has been definitively treated.
• Have a history of GI perforation within 12 months prior to enrollment (Cycle 1 Day 1).
• Major surgical procedure or significant traumatic injury ≤ 28 days prior to enrollment (≤ 56 days for hepatectomy, open thoracotomy or major neurosurgery) or anticipation of need for major surgical procedure during the course of the study.
• Serious, non-healing wound, ulcer, or bone fracture.
• Prior organ transplantation, including allogenic stem-cell transplantation.

Where it is running

• Hopital Prive Jean Mermoz — Lyon, France (enrolling)
• Hôpital La Timone - APHM — Marseille, France (enrolling)
• Hopital Saint Louis — Paris, France (enrolling)
• Centre Hospitalier Universitaire Reims — Reims, France (enrolling)
• Groupe Hospitalier Rance Emeraude — St-Malo, France (enrolling)
• Charite Universitaetsmedizin — Berlin, Germany (enrolling)
• Krankenhaus Nordwest — Frankfurt, Germany (enrolling)
• Istituto Tumori Bari Giovanni Paolo II — Bari, Bari, Italy (enrolling)
• A.O.U Careggi — Florence, Firenze, Italy (enrolling)
• Istituto Europeo Di Oncologia S.r.l. — Milan, Italy, Italy (enrolling)
• Azienda Unita Sanitaria Locale Della Romagna — Ravenna, Italy, Italy (enrolling)
• Humanitas Mirasole S.p.A. — Rozzano, Italy, Italy (enrolling)
• Azienda Ospedaliera Card. G. Panico — Tricase, LE, Italy (enrolling)
• Fondazione IRCCS Istituto Nazionale dei Tumori - Milano — Milan, Milan, Italy (enrolling)
• Azienda Ospedaliero Universitaria di Modena — Modena, Missouri, Italy (enrolling)
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma, RM, Italy (enrolling)
• Policlinico Tor Vergata Roma — Roma, Roma, Italy (enrolling)
• IFO-Regina Elena Institute for Cancer Research — Roma, Roma, Italy (enrolling)
• Azienda Sanitaria Universitaria Friuli Centrale — Udine, Udine, Italy (enrolling)
• Azienda Ospedaliera Universitaria Luigi Vanvitelli — Naples, Italy (enrolling)
• IRCCS Istituto Nazionale Tumori "Fondazione Giovanni Pascale" — Naples, Italy (enrolling)
• Fondazione IRCCS Istituto Oncologico Veneto — Padova, Italy (enrolling)
• U.O. Oncologia Medica 2 Universitaria - Azienda Ospedaliero-Universitaria Pisana Dipartimento di Ricerca Traslazionale e Nuove Tecnologie - University of Pisa — Pisa, Italy (enrolling)
• Hospital del Mar — Barcelona, Spain (enrolling)
• Hospital Universitario Virgen de las Nieves — Granada, Spain (enrolling)

Full record on ClinicalTrials.gov

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