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New treatment option for Colorectal Cancer
Official title Upfront Trastuzumab-Deruxtecan Plus Capecitabine and Bevacizumab for Patients With HER-2 Positive Metastatic Colorectal Cancer.
ClinicalTrials.gov ID: NCT07407465
What this study is testing
What is Trastuzumab-Deruxtecan (T-DXd)?
Trastuzumab-Deruxtecan (T-DXd) is an investigational medicine, given as an infusion into a vein, 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
- 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
- Phase 2: a mid-size study of how well it works
- This is a blinded study.
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
- Written informed consent obtained from the patient/legal representative before performing any protocol-related procedures, including screening...
- Patient state to comply with all the study procedures and treatments. Patients must be accessible for treatment and follow-up. Patients registered...
- Age ≥ 18 years at the time of informed consent.
- ECOG Performance Status ≤ 2.
- Life expectancy of ≥ 3 months.
You likely can't join if
- Have previously received any systemic anticancer therapy for CRC in the metastatic/locally advanced unresectable setting or have participated in any...
- Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with...
- 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...
- Patients with a medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York...
See the full eligibility criteria
Who can join
- 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.
- people 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...
- 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...
- 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
- ≥ 2 weeks or 5 half-lives (whichever is longer) from targeted agent- and small molecule-based therapy
- ≥ 6 weeks from nitrosureas or mitomycin C
- ≥ 1 week from TKIs approved for treatment of patients with non-small-cell lung cancer (baseline CT must be completed after discontinuation of TKI)
- \> 2 weeks from chloroquine/hydroxychloroquine
- ≥ 2 weeks from cell-free and Concentrated Ascites Reinfusion Therapy (CART), peritoneal shunt or drainage of ascites, pleural or pericardial effusion.
- Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative...
- Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception, presented in Table 1. From the time of screening and...
- Female participants must not donate, or retrieve for their own use, ova from the time of enrolment and throughout the study treatment period, and for at least 7 months after the final study drug administration. They...
- Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose of IP for T-DXd while 6 months for...
What rules you out
- Have previously received any systemic anticancer therapy for CRC in the metastatic/locally advanced unresectable setting or have participated in any treatment clinical trial for CRC in the metastatic/locally advanced...
- 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...
- 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...
- 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). people with troponin levels above...
- 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...
- 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...
- 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. people may be enrolled with chronic, stable Grade 2 toxicities (defined...
- 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...
- 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...
- 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...
- Serious, non-healing wound, ulcer, or bone fracture.
- Prior organ transplantation, including allogenic stem-cell transplantation.
- Known history of HIV infection.
- Active infection including tuberculosis, hepatitis B, hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if HCV RNA polymerase chain reaction (PCR) is negative. Patients with a past or...
- HBsAg negativity (for more than 6 months off anti-viral treatment).
- Anti-HBc positivity (IgG or total Ig).
- Absence of cirrhosis or fibrosis on prior imaging or biopsy.
- Absence of HCV co-infection and no history of HCV co-infection.
- Access to a local HBV expert during and after the study Patients meeting all abovementioned criteria must be closely monitored for HBV reactivation.
- Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan. Note: Patients, if...
- Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with trial requirements.
- Use of any disallowed drugs (see Section 7.5). Additional exclusion criteria for France and Germany:
- Patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency (uracilemia ≥ 16 ng/mL)
- Patient who is under judicial protection and patient who is legally institutionalized or under guardianship or not able to give consent.
The study team makes the final eligibility decision.
Where it's taking place
- Lyon, France
- Marseille, France
- Paris, France
- Reims, France
- St-Malo, France
- Berlin, Germany
- Frankfurt, Germany
- Bari, Bari, Italy
- Florence, Firenze, Italy
- Milan, Italy, Italy
- Ravenna, Italy, Italy
- Rozzano, Italy, Italy
- Tricase, LE, Italy
- Milan, Milan, Italy
- Modena, Missouri, Italy
- Roma, RM, Italy
- Roma, Roma, Italy
- Udine, Udine, Italy
- Naples, Italy
- Padova, Italy
+ 6 more site(s).
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 Lyon, France; Marseille, France; Paris, France; Reims, France; St-Malo, France; Berlin, Germany and 20 more location(s). Enter your location above to see the nearest site and check your eligibility.
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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.