Using Holmium-166 TARE for treating liver-limited unresectable colorectal cancer

Phase II Study Evaluating Holmium-166 TARE Followed by Maintenance Therapy in Liver Limited Unresectable Colorectal Cancer Patients After First-line Chemotherapy and Target Agents

This study is testing if a new liver treatment called Holmium-166 TARE, followed by personalized maintenance therapy, can help people with liver-limited colorectal cancer live longer without their disease getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Gruppo Oncologico del Nord-Ovest (Academic / other)
• Drugs / interventions: cetuximab, panitumumab, bevacizumab, chemotherapy
• Locations: 1 site (Pisa)
• Trial ID: NCT06332079 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of Holmium-166 TARE followed by maintenance therapy with fluoropyrimidine and either anti-EGFR or bevacizumab in patients with liver-limited unresectable colorectal cancer. The study includes two cohorts based on genetic mutations, with patients receiving tailored maintenance therapy after initial chemotherapy. The primary goal is to assess progression-free survival rates at 8 and 9 months for the respective cohorts. Patients must have shown a partial response or stable disease after prior treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed liver-limited unresectable colorectal adenocarcinoma who have achieved stable disease or partial response after initial chemotherapy.

Not a fit: Patients with colorectal cancer that has spread beyond the liver or those with significant comorbidities affecting treatment eligibility may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve progression-free survival in patients with liver-limited unresectable colorectal cancer.

How similar studies have performed: Other studies have shown promising results with similar targeted therapies in colorectal cancer, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Written informed consent to study procedures;
* Age ≥18 years;
* Histologically proven diagnosis of colorectal adenocarcinoma, with or without primary tumour in situ;
* Liver-only disease at radiological exams involving less than 50% of liver volume;
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2;
* Patients with partial response or stable disease according to RECIST 1.1 criteria deemed unresectable after 6-12 cycles of induction first-line chemotherapy;
* Life expectancy of at least 12 weeks;
* Hematopoietic function: absolute neutrophil count ≥ 1,500/mm3; platelet count

  ≥100,000/mm3; haemoglobin level ≥ 9 g/dL;
* Liver function: total bilirubin ≤ 1.5 times upper limit of normal (ULN); alkaline phosphatase

  ≤ 5 times ULN; AST ≤ 5 times ULN;
* Renal function: creatinine clearance \> 50 mL/min or serum creatinine 1.5 x UNL; no renal disease that would preclude study treatment or follow-up;
* Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient;
* Subjects and their partners must be willing to avoid pregnancy during the trial. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as outlined in Section 7.5 - Contraception, starting during study screening visit throughout the study period up to 180 days after the last dose of chemotherapy Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject;
* Will and ability to comply with the protocol

Inclusion criteria for Cohort A:

* RAS/BRAF wild-type and left sided primary tumor
* First-line induction chemotherapy regimen permitted up to 6-12 cycles with:

FOLFOX or FOLFIRI + anti-EGFR (cetuximab or panitumumab). Patients who interrupted anti-EGFR target therapy during induction phase due to toxicity or other reasons, candidate to maintenance with fluoropyridine alone therapy can be enrolled.

Inclusion criteria for Cohort B:

* RAS mutated and/or right-sided primary tumor
* First-line induction chemotherapy regimen admitted up to 6-12 cycles with:

FOLFOX/FOLFIRI/XELOX + bevacizumab or FOLFOXIRI + bevacizumab. Patients who interrupted bevacizumab during induction phase due to toxicity or other reasons, candidate to maintenance with fluoropyridine alone therapy can be enrolled.

Exclusion Criteria:

* Patients with radiological evidence of extra liver distant metastases.
* Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis, or any other contraindications to radioembolization treatment;
* Previous radiotherapy delivered to the liver;
* Patients with BRAF mutated and/or MSI-high tumours;
* Previous history of malignancy within the last 5 years will be excluded with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ;
* Treatment with any investigational drug within 30 days prior to enrolment or 2 investigational agent half-lives (whichever is longer);
* Active uncontrolled infections or other clinically relevant concomitant illness contraindicating study procedures and treatment administration Clinically significant (e.g. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication
* Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study and until 180 days after the last trial treatment;
* History of a previous allergic reaction to contrast media that would preclude safe angiography of the hepatic arteries, in the opinion of the treating Interventional Radiologist;
* Known hypersensitivity to fluoropyrimidine, anti-VEGF or anti-EGFR MoAb.
* Psychiatric or addictive disorders, or other conditions that, in the opinion of the investigator, would preclude study participation;
* Withdrawal of the consent to take part to the study

Where this trial is running

Pisa

• Azienda Ospedaliero Universitaria Pisana — Pisa, Italy (Recruiting)

Study contacts

• Principal investigator: Gianluca Masi, MD — Azienda Ospedaliero, Universitaria Pisana
• Study coordinator: Gianluca Masi, MD

Conditions Colorectal Cancer Metastatic; HOLMIUM; TARE; Maintenance therapy; Liver-limited colorectal cancer; Unresectable colorectal cancer