Holmium-166 TARE in Liver Limited Unresectable Colorectal Cancer Patients

NCT06332079 | Terminated Phase 2

• 1 other identifier: HAITI 2023-505356-22-00
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to assess the efficacy of 166Ho-TARE followed by maintenance therapy with fluoropyrimidine and anti-EGFR or bevacizumab in liver-limited unresectable colorectal cancer patients, in terms of progression free rate 9- and 8-months for cohort A and B, respectively.

Conditions

Colorectal Cancer Metastatic

Keywords

HOLMIUM; TARE; Maintenance therapy; Liver-limited colorectal cancer; Unresectable colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS) Rate

  PFS is defined as the time from study enrolment to the first documentation of objective disease progression or death due to any cause, whichever occurs first. PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive, on study and progression free at the time of the analysis.

  36 months

Secondary Outcomes (9)

• Overall Toxicity rate

  36 months

• Grade 3/ Grade 4 Toxicity rate

  36 months

• Post-treatment Disease Control Rate (DCR)

  36 months

• Progression free survival

  36 months

• Overall Survival

  36 months

Study Arms (1)

COHORT A/B

EXPERIMENTAL

Eligible patients will receive Scout dose procedure. After 1-2 weeks, patients eligible for radioembolization will receive 166Ho-TARE and at least after 3 weeks, maintenance treatment with fluoropyrimidine plus target agents (anti-EGFR or bevacizumab) according to the respective study cohort. Maintenance treatment: Cohort A: * CETUXIMAB iv day1, over 1 hours, 500 mg/sqm or PANITUMUMAB iv over 1 hours, 6 mg/kg, every 14 days * LED 200 mg/sqm iv over 1 hour, day 1 * 5-FLUOROURACIL ic 48 h, starting on day 1 every 14 days; 2400 mg/sqm and 400 mg/sqm bolus if FOLFOX/FOLFIRI in the induction treatment Cohort B: * BEVACIZUMAB 5 mg/kg iv biweekly day1, over 30 minutes * LED 200 mg/sqm iv over 1 hour, day 1 * 5-FLUOROURACIL ic 48 h, starting on day 1 every 14 days; 2400 mg/sqm and 400 mg/sqm bolus if FOLFOX/FOLFIRI in the induction treatment CAPECITABINE, 1000 mg/sqm orally twice daily, day 1-14, plus bevacizumab 7,5 mg/kg iv every 21 days is allowed.

Procedure: 166Holmium TARE; Drug: Cetuximab; Drug: Panitumumab; Drug: 5-Fluorouracil; Drug: Bevacizumab; Drug: Capecitabine

Interventions

166Holmium TARE PROCEDURE

166Ho-TARE treatment comprises of two hospital visits: one for a work-up procedure and another for the therapy procedure, with usually a 1-2 weeks interval.

COHORT A/B

Cetuximab DRUG

Target agent

COHORT A/B

Panitumumab DRUG

Target agent

COHORT A/B

Capecitabine DRUG

Chemotherapy

COHORT A/B

5-Fluorouracil DRUG

Chemotherapy

COHORT A/B

Bevacizumab DRUG

Target agent

COHORT A/B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (1)

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126, Italy

Location

MeSH Terms

Interventions

Cetuximab; Panitumumab; Fluorouracil; Bevacizumab; Capecitabine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Gianluca Masi, MD

  Azienda Ospedaliero, Universitaria Pisana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two cohorts of patients will be included according to the two main prognostic populations in mCRC (left sided, RAS/BRAF wild-type and, right-sided and/or RAS mutated tumors) treated with different maintenance therapy (fluoropyrimidine plus anti-EGFR or bevacizumab). A total of 23 patients will be enrolled in each cohort.

Study Record Dates

• First Submitted: March 8, 2024
• First Posted: March 27, 2024
• Study Start: March 13, 2024
• Primary Completion: December 16, 2025
• Study Completion: December 16, 2025
• Last Updated: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)