Authorised Therapeutic exploratory (Phase II) Refractory Metastatic Colorectal Cancer with Liver Dominant Disease

Randomized Study to Evaluate Melphalan/HDS Treatment Followed by Trifluridine–tipiracil plus Bevacizumab Versus Trifluridine–tipiracil plus Bevacizumab Alone in Metastatic Colorectal Cancer Patients

EU CTIS ID: 2024-520356-24-00

What this study is testing

To evaluate the effect of Melphalan/HDS followed by trifluridine–tipiracil plus bevacizumab on hepatic progression free survival (hPFS) compared to that of trifluridine–tipiracil plus bevacizumab alone in patients with liver dominant metastatic colorectal cancer (mCRC).

  • Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • Patient is ≥ 18 years of age on day of consent.
  • If patient is a woman of childbearing potential (WOCBP) (i.e., fertile meaning not permanently sterilized and having had a menstrual period within the past 12 months), has a negative serum pregnancy test (β-human chorionic gonadotropin β-HCG) within 7 days prior to randomization.
  • If patient is a WOCBP or fertile male (not permanently sterile by bilateral orchiectomy), they or their partner must be willing to use a highly effective contraception method (e.g., combined hormonal contraception; progestogen-only hormonal contraception; intrauterine device, intrauterine hormone-releasing system; bilateral tubal occlusion, vasectomized partner or sexual abstinence) from consent to at least 6 months after the last administration of study treatment.
  • Signed informed consent.
  • Histologically confirmed diagnosis of mCRC and histologically or cytologically proven CRC metastases that occupy 50% or less of the liver parenchyma.
  • Patient has liver-dominant metastatic disease. Liver-dominant is defined as the majority of total tumor burden is located in the liver, and the liver lesions are not resectable or treatable with ablation or are associated with extrahepatic disease that makes surgical intervention non-curative

You likely can't join if

  • Patient has Child-Pugh Class B or C cirrhosis or evidence of clinically significant portal hypertension by history, endoscopy, or radiologic studies (large abdominal varices, prior history of varices by endoscopy).
  • Patient is taking immunosuppressive drugs. NOTE: Oral corticosteroids ≤ 10 mg/day are allowed.
  • Patient is unable to be temporarily removed from chronic anti-coagulation therapy.
  • Patient has active bacterial infection(s) with systemic manifestations (malaise, fever, leucocytosis).
  • Patient has an active infection, including Hepatitis B and Hepatitis C infection. NOTE: Patients with anti-hepatitis B core antibody (HBc) positive, or hepatitis B surface antigen (HBsAg) but DNA negative are allowed exception(s).
  • Patient has known severe allergic reaction to iodine contrast that cannot be controlled by premedication with antihistamines and steroids.
See the full eligibility criteria
Who can join
  • Patient is ≥ 18 years of age on day of consent.
  • If patient is a woman of childbearing potential (WOCBP) (i.e., fertile meaning not permanently sterilized and having had a menstrual period within the past 12 months), has a negative serum pregnancy test (β-human chorionic gonadotropin β-HCG) within 7 days prior to randomization.
  • If patient is a WOCBP or fertile male (not permanently sterile by bilateral orchiectomy), they or their partner must be willing to use a highly effective contraception method (e.g., combined hormonal contraception; progestogen-only hormonal contraception; intrauterine device, intrauterine hormone-releasing system; bilateral tubal occlusion, vasectomized partner or sexual abstinence) from consent to at least 6 months after the last administration of study treatment.
  • Signed informed consent.
  • Histologically confirmed diagnosis of mCRC and histologically or cytologically proven CRC metastases that occupy 50% or less of the liver parenchyma.
  • Patient has liver-dominant metastatic disease. Liver-dominant is defined as the majority of total tumor burden is located in the liver, and the liver lesions are not resectable or treatable with ablation or are associated with extrahepatic disease that makes surgical intervention non-curative
  • Disease in the liver must be measurable (per RECIST v1.1 guidelines) by computed tomography (CT) and/or magnetic resonance imaging (MRI).
  • Patient weighs ≥ 35 kg (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein required with Melphalan/HDS).
  • If there is evidence of extrahepatic metastatic disease, it is limited, and the life-threatening component of disease is in the liver. Limited extrahepatic disease is defined in this protocol as follows: up to 5 tumor lesions in the lung with longest diameter not greater than 2 cm and/or up to 5 lymph nodes that measure 2 cm or less per lesion
  • Scans used to determine eligibility (CT scan of the chest/abdomen/pelvis and MRI of the liver) must be performed within 28 days prior to randomization.
  • Patient was previously treated and progressed on, or following, or developed intolerance to, fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and/or an anti-EGFR therapy if RAS wild-type. Patient with MSI-H/dMMR CRC was previously treated and progressed on or following, or developed intolerance to, immune checkpoint inhibitor (ICPI) therapy, if eligible.
  • Patient has an ECOG PS of 0-1 within 14 days prior to randomization
What rules you out
  • Patient has Child-Pugh Class B or C cirrhosis or evidence of clinically significant portal hypertension by history, endoscopy, or radiologic studies (large abdominal varices, prior history of varices by endoscopy).
  • Patient is taking immunosuppressive drugs. NOTE: Oral corticosteroids ≤ 10 mg/day are allowed.
  • Patient is unable to be temporarily removed from chronic anti-coagulation therapy.
  • Patient has active bacterial infection(s) with systemic manifestations (malaise, fever, leucocytosis).
  • Patient has an active infection, including Hepatitis B and Hepatitis C infection. NOTE: Patients with anti-hepatitis B core antibody (HBc) positive, or hepatitis B surface antigen (HBsAg) but DNA negative are allowed exception(s).
  • Patient has known severe allergic reaction to iodine contrast that cannot be controlled by premedication with antihistamines and steroids.
  • Patient has a history of or known hypersensitivity to melphalan or the components of the Melphalan/HDS system.
  • Patient has known latex allergy.
  • Patient has a history of known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia.
  • Patient has an uncontrolled endocrine disorder including diabetes mellitus, hypothyroidism, or hyperthyroidism.
  • Patient received anti-cancer therapy including radiotherapy or investigational agent for any indication ≤ 30 days prior to randomization.
  • Patient has New York Heart Association functional classification II, III or IV active cardiac condition(s), including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias, or severe valvular disease that create(s) undue risks of undergoing general anesthesia.
  • Patients should have recovered to Grade 1 or less for AEs related to prior treatment unless deemed clinically not significant, such as lymphopenia, anemia or Grade 2 neuropathy due to prior oxaliplatin treatment. NOTE: Certain side effects that are unlikely to develop into serious or life–threatening events (e.g., alopecia) are allowed at ≥ Grade 1.
  • Patient is less than 28 days after surgery and surgical wound is not fully healed.
  • Patient is currently under treatment for cancer other than mCRC or is not deemed to be cancer free.
  • Patient was previously treated with trifluridine–tipiracil.
  • Patient has history of allergic reactions attributed to compounds of similar composition to trifluridine/tipiracil or any of its excipients.
  • Patient has hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
  • Patient has history of allergic reactions or hypersensitivity to bevacizumab or any of its excipients.
  • Patient has history of hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies.
  • Contraindications to bevacizumab, including uncontrolled hypertension, history of active fistula or bowel perforation (unless in the setting of a resected primary), history of cerebrovascular accident or arterial thrombotic event in the last 1 year, or history of venous thrombotic event in the last 30 days.
  • Evidence of hepatic vein or portal vein thrombosis.
  • Patient has history or evidence of clinically significant pulmonary disease or any other condition that precludes the use of general anesthesia.
  • Prior chemoembolization or radioembolization to the liver or prior hepatic arterial infusion therapy.
  • Albumin level < 3.0 g/dL.
  • Patient has a history of bleeding disorders, presence of brain metastases, or other intracranial abnormalities that would put them at risk for bleeding with anti-coagulation.
  • Patient has known varices at risk of bleeding, including medium or large esophageal or gastric varices, active peptic ulcer, or history of recent hemoptysis.
  • Patient has an active second malignancy or has a history of recent definitively treated invasive cancer within 2 years prior to enrolment, with the exception of non-melanoma skin cancer.
  • Patient has peritoneal lesions or large abdominal masses.
  • Patient is pregnant or breastfeeding.
  • Patient is a WOCBP (i.e., fertile meaning not permanently sterilized and having had a menstrual period within the past 12 months) who is unable to undergo hormonal suppression to avoid menstruation during treatment.

The study team makes the final eligibility decision.

Where it's taking place

  • United States
  • Turkey
  • Serbia
  • United Kingdom

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, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; Turkey; Serbia; United Kingdom. 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 EU CTIS; the study team decides eligibility.