High Dose Melphalan + Cancer Treatment for Metastatic Colorectal Cancer

(DEL-LIVER Trial)

Recruiting at 1 trial location

Overseen By Matthew Cooney, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Delcath Systems Inc.

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Cirrhosis, Cardiac conditions, Pulmonary disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a liver-focused high-dose chemotherapy treatment with Melphalan, followed by standard cancer therapy, is safe and effective for individuals whose colorectal cancer has spread to the liver. Researchers will compare this approach to standard cancer treatment alone. The trial seeks participants with colorectal cancer primarily spread to the liver who have not responded to other treatments. Participants must attend regular checkups every two weeks and undergo scans every two months. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you must be able to temporarily stop chronic anti-coagulation therapy and should not have received anti-cancer therapy within 30 days prior to randomization.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using melphalan for liver treatment appears promising. Studies have found that injecting melphalan directly into the liver's blood supply is safe and feasible for some cancer patients. For instance, one study with patients whose eye cancer spread to the liver demonstrated that this method could be used without major safety issues.

Researchers are also evaluating the safety of combining melphalan with trifluridine-tipiracil and bevacizumab. Although specific data on this exact combination for colon cancer is lacking, trifluridine-tipiracil and bevacizumab are already common treatments for metastatic colon cancer, suggesting these drugs are generally safe.

In summary, melphalan has proven safe in certain liver treatments, and the other drugs are standard treatments, indicating a reasonable safety profile for the combination being tested. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment involving high-dose Melphalan because it offers a unique approach to tackling metastatic colorectal cancer. Unlike standard options like Trifluridine-tipiracil plus Bevacizumab, this treatment delivers Melphalan directly into the hepatic artery, potentially allowing for higher drug concentrations at the tumor site while minimizing systemic side effects. This targeted delivery system is designed to enhance the drug's effectiveness against liver metastases, which are common in colorectal cancer. By combining this with subsequent consolidation treatment, the strategy aims to improve outcomes beyond what's achievable with current therapies.

What evidence suggests that this trial's treatments could be effective for metastatic colorectal cancer?

Research has shown that delivering melphalan directly into the liver can effectively treat cancers that have spread there. In earlier studies, about half of the patients responded positively, with their cancer either shrinking or stopping its growth. On average, the cancer did not worsen for about 7.4 months, and many patients lived up to 24.8 months after receiving the treatment.

In this trial, one group of participants will receive melphalan followed by consolidation treatment with trifluridine-tipiracil and bevacizumab. Another group will receive only trifluridine-tipiracil and bevacizumab, which are already approved for treating advanced colorectal cancer. These drugs are known to slow cancer growth and help patients live longer. The combination aims to enhance treatment effectiveness by targeting the cancer directly in the liver. ^{1 2 5 6 7}

Who Is on the Research Team?

Marwan Fakih, MD

Principal Investigator

City of Hope Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic colorectal cancer that has spread to the liver, but not beyond 50% of it. They should have tried and not responded well to standard treatments including chemotherapy and biological therapies. Their physical condition must be relatively good (ECOG PS 0-1), and they need measurable liver disease according to specific guidelines.

Inclusion Criteria

My colorectal cancer has spread to my liver but occupies 50% or less of it.

I have been mostly active and able to carry out all pre-disease activities without restriction recently.

Most of my cancer is in my liver and cannot be surgically removed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive melphalan/HDS treatment administered twice, 8 weeks apart, with tumor response assessed every 8 weeks

10 weeks

2 visits (in-person) for melphalan/HDS treatment

Consolidation Treatment

Participants receive trifluridine-tipiracil plus bevacizumab treatment until disease progression or unacceptable toxicity

Until disease progression

Clinic visits every 2 weeks for checkups and tests

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Scans approximately every 2 months

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Melphalan
• Trifluridine-tipiracil

Trial Overview The study tests high dose Melphalan chemotherapy delivered directly into the liver followed by Trifluridine-tipiracil plus Bevacizumab treatment, compared with just the latter treatment alone. It aims to see if this combination is more effective in treating liver-dominant colorectal cancer.

How Is the Trial Designed?

Group I: Melphalan/HDS followed by Consolidation Treatment with Trifluridine-tipiracil plus Bevacizumab Experimental Treatment 1 Intervention

Melphalan/HDS is given as an infusion of Melphalan into the hepatic artery under general anesthesia. This treatment is administered twice, 8 weeks apart. Following 2 treatments with Melphalan/HDS, Trifluridine-tipiracil is given 35 mg/m2 up to a maximum of 80 mg per dose orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle; and intravenous (IV) bevacizumab 5 mg/kg body weight on Days 1 and 15 of each 28-day cycle until disease progression or unacceptable toxicity

Group II: Trifluridine-tipiracil plus Bevacizumab Alone Active Control 1 Intervention

Trifluridine-tipiracil plus Bevacizumab is the standard of care for patients with metastatic colorectal cancer. Trifluridine-tipiracil is given 35 mg/m2 up to a maximum of 80 mg per dose orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle; and intravenous (IV) bevacizumab 5 mg/kg body weight on Days 1 and 15 of each 28-day cycle until disease progression or unacceptable toxicity

Who Is Running the Clinical Trial?

Delcath Systems Inc.

Lead Sponsor

Trials

11

Recruited

970+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06607458

Study Details | NCT06607458 | Evaluation of the Safety ... This is an open-label, randomized, multi-center study in which patients with liver dominant refractory mCRC will be randomized 2:1 to receive melphalan/HDS (2 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6388637/

Hepatic artery infusion of melphalan in patients with liver ... The current study is the first to demonstrate that hepatic arterial infusion of melphalan is a safe and feasible treatment option for ocular melanoma patients.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0748798307000868

Hepatic artery infusion of high-dose melphalan at reduced ... Twelve patients showed hepatic response, with a median duration of response of 11.5 months, according to WHO criteria. Although HI–HPP results in high perfusate ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)41606-2/fulltext

Isolated hepatic melphalan perfusion of colorectal liver ... Hepatic response rate was 50% with a median progression-free and overall survival of, respectively, 7.4 and 24.8 months. In multivariate analyses, absence of ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01705

Isolated Hepatic Perfusion With Melphalan for Patients ... The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419416062

Isolated hepatic melphalan perfusion of colorectal liver ... Hepatic response rate was 50% with a median progression-free and overall survival of, respectively, 7.4 and 24.8 months. In multivariate analyses, absence of ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)39395-0/fulltext

Management of isolated nonresectable liver metastases in ... Median overall survival was 25.0 [95% confidence interval (CI) 19.4–30.6] months for IHP and 21.7 (95% CI 19.6–23.8) months for systemic treatment and did not ...