Evaluation of the Safety and Efficacy of Treatment w/High Dose Melphalan Given Directly Into the Liver Followed by Treatment w/Approved Cancer Treatment or Approved Cancer Treatment Alone in Patients w/ Metastatic Breast Cancer w/Liver Dominant Disease
An Open-label, Randomized, Multi-Center Study to Evaluate the Efficacy and Safety of Induction Treatment With Melphalan/HDS Followed by Consolidation Treatment With Eribulin or Vinorelbine or Capecitabine Versus Eribulin or Vinorelbine or Capecitabine Alone in Patients With Metastatic Breast Cancer With Liver Dominant Disease
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study is for people with breast cancer that has spread mainly to the liver. It tests high-dose melphalan, a chemotherapy drug given directly into the liver, followed by approved cancer treatment, compared with approved cancer treatment alone. Researchers want to learn how safe the liver treatment is and how well it works.
The goal of this clinical trial is to learn if using a liver-directed therapy with high dose chemotherapy followed by approved cancer treatment to treat patients with breast cancer that has spread to the liver is safe and tolerable. The clinical trial will also learn if the liver-directed therapy with high dose chemotherapy works on the disease in the liver. Investigators will compare the use of the liver-directed therapy with high dose chemotherapy followed by approved cancer treatment or approved cancer treatment alone. Participants will: * Undergo up to two cycles of liver-directed therapy with high dose chemotherapy procedures followed by approved cancer treatment or take approved cancer treatment alone * Visit clinic at least every two weeks for checkups and tests * Complete scans approximately every 8 weeks
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Have breast cancer confirmed by a tissue test that has spread and is HER2-negative, including triple-negative breast cancer.
- If the cancer uses hormones to grow, it must have worsened on hormone treatment and CDK 4/6 drugs, or you could not tolerate those treatments.
- Cancer must have worsened after certain antibody-linked cancer drugs, such as sacituzumab govitecan or trastuzumab deruxtecan, unless these drugs are not suitable. Where they are not available as standard care, two standard chemotherapy treatments must have failed or caused side effects you could not tolerate.
- Be able to receive chemotherapy with one drug: eribulin, vinorelbine, or capecitabine.
- Most cancer, or the life-threatening part, must be in the liver. Cancer must affect no more than half of the liver.
- Cancer outside the liver must be limited to the breast, lungs, other internal organs, lymph nodes, or skin. If present, the life-threatening cancer must be in the liver.
- Liver tumors must be measurable on CT or MRI scans. Required chest, belly, pelvis, and liver scans must be done within 28 days before study group assignment.
- Weigh at least 35 kg (about 77 pounds) and be fully active or able to do light work despite some limits on hard physical activity.
Who can't join
- Have had treatment through the liver's arteries, including chemotherapy infusion or procedures that block blood flow and deliver chemotherapy or radiation. Also excluded: serious high pressure in the liver's blood vessels or blood albumin, a protein, below 3.0 g/dL.
- Have certain heart conditions or serious lung disease that make anesthesia unsafe, or an uncontrolled hormone condition such as diabetes or thyroid disease.
- Have bleeding risks, including a bleeding disorder, brain tumors or other brain problems that make blood thinners risky, swollen veins at risk of bleeding, an active stomach ulcer, or recent coughing up blood. You also cannot join if you cannot pause long-term blood thinners.
- Have another active cancer or an invasive cancer treated within the past two years, with exceptions for certain well-treated, controlled skin or thyroid cancers. Also excluded: serious signs of worsening cancer, such as pressure on the spinal cord, rising pain or oxygen needs, or risk of a broken bone.
- Are pregnant or breastfeeding. If you can become pregnant, you must be able to take hormone treatment to stop periods during treatment.
- Have an active infection, including hepatitis B or C, with some exceptions for hepatitis B tests when no viral DNA is found. Long-term drugs that weaken the immune system are not allowed, except low-dose steroids within the study limit.
- Have an allergy to melphalan, parts of its treatment system, latex, or heparin, or a history of low platelets caused by heparin. A severe iodine contrast allergy also excludes you if medicines cannot control it.
- Had cancer treatment within 30 days before study group assignment; still have more than mild treatment side effects, with some exceptions; or had surgery less than 28 days ago and the wound has not fully healed.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * Histologically confirmed diagnosis of MBC. * Patients with HER2-negative (IHC 0 or 1+ or 2+ and ISH non-amplified) MBC (including triple negative disease). * Patient with Hormone Receptor-Positive disease has progressed on or intolerant of prior endocrine therapy and CDK 4/6 inhibitors. * Disease progression after TOPO-1 isomerase inhibitor payload ADC, such as sacituzumab govitecan and/or trastuzumab deruxtecan. Patients not eligible or suitable for ADCs can be considered for this study. NOTE: In jurisdictions where those ADCs are not available as standard of care, patients will be eligible after prior treatment or intolerable toxicity on two standard chemotherapy regimens for the appropriate disease subtype. * Patient with HER2-negative breast cancer suitable for single agent chemotherapy as per judgement of treating investigator. * Patient is a suitable candidate for treatment with one of the following: eribulin, vinorelbine, or capecitabine as per judgement of treating investigator. * Patient has liver dominant metastatic disease. Liver-dominant is defined as the majority of total tumor burden is located in the liver, and/or the life-threatening component of the disease is located in the liver. * MBC metastases must involve ≤ 50% of the liver parenchyma. * If there is evidence of extrahepatic metastatic disease, it is limited, and the life-threatening component of disease is in the liver. Extrahepatic disease is restricted to lesions in the breast, lung, other visceral organs, lymph nodes and skin. * 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 * 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 has an ECOG PS of 0-1. Exclusion Criteria: * Prior chemoembolization or radioembolization to the liver or prior hepatic arterial infusion therapy. * Evidence of clinically significant portal hypertension by history, endoscopy, or radiologic studies (large abdominal varices, prior history of varices by endoscopy). * New York Heart Association functional classification II, III or IV or 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. * History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia. * History of bleeding disorders, presence of brain metastases or other intracranial abnormalities that would put them at risk for bleeding with anti-coagulation. * Known varices at risk of bleeding, including medium or large esophageal or gastric varices, active peptic ulcer, or history of recent hemoptysis. * An active second malignancy or has a history of recent definitively treated invasive cancer within 2 years prior to enrolment. Exceptions are optimally treated and controlled basal cell carcinoma, other skin cancers, thyroid cancer. * Symptoms and signs indicating clinically significant progression of disease including cord compression, increasing pain symptoms, increasing oxygen requirements, impending pathological fracture, compressive lymphadenopathy, or symptomatic pleural effusion. * Pregnant or breastfeeding. * 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. * Patient requires chronic use of immunosuppressive drugs. NOTE: Oral prednisolone ≤ 10 mg/day or equivalent is allowed. * Unable to be temporarily removed from chronic anti-coagulation therapy. * Active bacterial infections with systemic manifestations (malaise, fever, leucocytosis). * 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). * Known severe allergic reaction to iodine contrast that cannot be controlled by premedication with antihistamines and steroids. * History of or known hypersensitivity to melphalan or the components of the Melphalan/HDS system. * Known latex allergy. * History of known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia. * Uncontrolled endocrine disorder including diabetes mellitus, hypothyroidism, or hyperthyroidism. * Received anti-cancer therapy including radiotherapy or investigational agent for any indication ≤ 30 days prior to randomization. * 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 taxane treatment. NOTE: Certain side effects that are unlikely to develop into serious or life-threatening events (e.g., alopecia) are allowed at ≥ Grade 1. * \< 28 days after surgery and surgical wound is not fully healed. * Currently under treatment for cancer other than MBC or is not deemed to be cancer free. * Not eligible to receive either eribulin or vinorelbine or capecitabine. * Albumin level \< 3.0 g/dL.
Study sites (5)
CA
- University of California Los Angeles · Santa Monica, CA 90404More trials in Santa Monica
FL
- Moffitt Cancer Center · Tampa, FL 33612More trials in Tampa
OH
- Cleveland Clinic · Cleveland, OH 44106More trials in Cleveland
- Ohio State University, Stefanie Spielman Comprehensive Breast Center · Columbus, OH 43212More trials in Columbus
TX
- UT Southwestern Medical Center · Dallas, TX 75325More trials in Dallas