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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Delcath Systems Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Dec 2025 → ongoing

Decision date (initial)

2025-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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).

Secondary objectives 3

1. To further evaluate the anti-tumor efficacy of Melphalan/HDS followed by trifluridine–tipiracil plus bevacizumab compared to trifluridine–tipiracil plus bevacizumab alone in patients with liver dominant mCRC.
2. To evaluate the safety and tolerability of Melphalan/HDS followed by trifluridine–tipiracil plus bevacizumab compared to trifluridine–tipiracil plus bevacizumab alone in patients with liver dominant mCRC.
3. To characterize the local and systemic exposure of melphalan administered by the HDS.

Conditions and MedDRA coding

Refractory Metastatic Colorectal Cancer with Liver Dominant Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patient is ≥ 18 years of age on day of consent.
2. Histologically confirmed diagnosis of mCRC and histologically or cytologically proven CRC metastases that occupy 50% or less of the liver parenchyma.
3. 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
4. Disease in the liver must be measurable (per RECIST v1.1 guidelines) by computed tomography (CT) and/or magnetic resonance imaging (MRI).
5. Patient weighs ≥ 35 kg (due to possible size limitations with respect to percutaneous catheterization of the femoral artery and vein required with Melphalan/HDS).
6. 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
7. 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.
8. 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.
9. Patient has an ECOG PS of 0-1 within 14 days prior to randomization
10. 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.
11. 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.
12. Signed informed consent.

Exclusion criteria 31

1. 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).
2. 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.
3. Patient has history or evidence of clinically significant pulmonary disease or any other condition that precludes the use of general anesthesia.
4. 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.
5. Patient has known varices at risk of bleeding, including medium or large esophageal or gastric varices, active peptic ulcer, or history of recent hemoptysis.
6. 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.
7. Patient has peritoneal lesions or large abdominal masses.
8. Patient is pregnant or breastfeeding.
9. 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.
10. Patient is taking immunosuppressive drugs. NOTE: Oral corticosteroids ≤ 10 mg/day are allowed.
11. Patient is unable to be temporarily removed from chronic anti-coagulation therapy.
12. Patient has active bacterial infection(s) with systemic manifestations (malaise, fever, leucocytosis).
13. 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).
14. Patient has known severe allergic reaction to iodine contrast that cannot be controlled by premedication with antihistamines and steroids.
15. Patient has a history of or known hypersensitivity to melphalan or the components of the Melphalan/HDS system.
16. Patient has known latex allergy.
17. Patient has a history of known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia.
18. Patient has an uncontrolled endocrine disorder including diabetes mellitus, hypothyroidism, or hyperthyroidism.
19. Patient received anti-cancer therapy including radiotherapy or investigational agent for any indication ≤ 30 days prior to randomization.
20. 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.
21. Patient is less than 28 days after surgery and surgical wound is not fully healed.
22. Patient is currently under treatment for cancer other than mCRC or is not deemed to be cancer free.
23. Patient was previously treated with trifluridine–tipiracil.
24. Patient has history of allergic reactions attributed to compounds of similar composition to trifluridine/tipiracil or any of its excipients.
25. Patient has hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
26. Patient has history of allergic reactions or hypersensitivity to bevacizumab or any of its excipients.
27. Patient has history of hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies.
28. 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.
29. Evidence of hepatic vein or portal vein thrombosis.
30. Prior chemoembolization or radioembolization to the liver or prior hepatic arterial infusion therapy.
31. Albumin level < 3.0 g/dL.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. hPFS (time from randomization to the first occurrence of hepatic disease progression or death due to any cause)

Secondary endpoints 8

1. Progression free survival (PFS)
2. Objective response rate (ORR) (complete response [CR] + partial response [PR])
3. Hepatic ORR (hORR)
4. Duration of response (DOR)
5. Hepatic DOR (hDOR)
6. Disease control rate (DCR)
7. Hepatic DCR (hDCR)
8. Overall survival (OS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Delcath Systems Inc.

Sponsor organisation

Delcath Systems Inc.

Address

566 Queensbury Avenue

City

Queensbury

Postcode

12804

Country

United States

Scientific contact point

Organisation

Delcath Systems Inc.

Contact name

Ashleigh Lamson

Public contact point

Organisation

Delcath Systems Inc.

Contact name

Ashleigh Lamson

Third parties 4

Locations

5 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications