FTD-TPI, Bevacizumab, and Radioembolization With 166Ho-microspheres in Refractory Metastatic Colorectal Cancer

NCT06563986 | Recruiting Phase 2 DMC

• 1 other identifier: NL85987.041.24
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Extrahepatic disease progression limits clinical efficacy of individualized radioembolization for patients with refractory metastatic colorectal cancer (mCRC). In the same patient population, trifluridine/tipiracil (FTD-TPI) and bevacizumab lead to disease control and overall survival benefit and may be a radiosensitizer. The purpose of this study is to determine safety, tolerability, and activity of individualized radioembolization with 166Holmium (166Ho)-microspheres combined with FTD-TPI and bevacizumab.

Conditions

Metastatic Colorectal Cancer

Keywords

Radioembolization; Trifluridine/Tipiracil; Refractory Metastatic Colorectal Cancer; Radioembolization With 166Ho-microspheres

Outcome Measures

Primary Outcomes (1)

• Hepatic objective response rate (hORR) (PERCIST 1.0)

  Hepatic objective response rate (hORR) will be assessed by Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0.

  Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.

Secondary Outcomes (11)

• Hepatic objective response rate (hORR) (RECIST 1.1)

  Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.

• Overall and extra-hepatic ORR (RECIST 1.1)

  Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.

• Overall and extra-hepatic ORR (PERCIST 1.0)

  Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.

• Serious adverse events (SAE's)

  Evaluated every 8 weeks after start treatment during the first half year. The collection period will start from the first day of the first treatment cycle until 180 days thereafter.

• Grade ≥3 adverse events (CTCAE 5.0)

  Evaluated every 8 weeks after start treatment during the first half year. The collection period will start from the first day of the first treatment cycle until 180 days thereafter.

Other Outcomes (1)

• Dosimetry scout + post treatment 1 and 2

  Evaluated immediately after the radioembolization treatment.

Study Arms (1)

Intervention: Systemic treatment (FTD-TPI + bevacizumab) and radioembolization

EXPERIMENTAL

* Individualized dose 166Ho radioembolization, combined with systemic treatment: * 35 mg/m2 FTD-TPI on day 1-5 and 8-12 every 4 weeks * 5 mg/kg bevacizumab iv. on day 1 and 15 every 4 weeks

Drug: Systemic treatment (FTD-TPI and bevacizumab); Device: Radioembolization with 166-Ho microspheres

Interventions

Systemic treatment (FTD-TPI and bevacizumab) DRUG

Systemic treatment (FTD-TPI and bevacizumab) administration is according to standard clinical practice. Each treatment cycle will be 28 days in duration. One treatment cycle consists of the following: * Days 1-5: oral intake of FTD-TPI and bevacizumab IV infusion on day 1 * Days 8-12: oral intake of FTD-TPI * Day 15: bevacizumab IV infusion Bevacizumab 5.0mg/kg i.v. is repeated every 2 weeks. If toxicity occurs, dose modifications and dose delays should be administered and applied according to standard practice.

Intervention: Systemic treatment (FTD-TPI + bevacizumab) and radioembolization

Radioembolization with 166-Ho microspheres DEVICE

Individualized 166Ho radioembolization will be performed via a catheter during angiography. Before the treatment, a scout procedure will be performed to determine individualized 166Ho dose of the treatment. Dosimetry-based treatment planning will be individualized using Q- Suite software. In case of bilateral disease, patients will be treated in two procedures to each hemi-liver, separated by 1 month. Before the first procedure, a scout procedure will be performed in which the individualized 166Ho dose of the first and second procedure will be calculated.

Intervention: Systemic treatment (FTD-TPI + bevacizumab) and radioembolization

Eligibility Criteria

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

You may qualify if:

• Unresectable liver dominant mCRC
• Prior therapy with fluoropyrimidine, oxaliplatin, and irinotecan for the treatment of metastatic colorectal cancer and had demonstrated progressive disease or intolerance to their last regimen
• Patients who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be eligible to enter the study.
• Patients who refuse oxaliplatin or irinotecan will also be eligible to enter the study.
• Patients who had received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy count the adjuvant therapy as treatment of metastatic colorectal cancer.
• Written informed consent
• Age \>=18 years
• Estimated hepatic tumor replacement ≥ 10% and ≤ 50% of total liver volume Eastern Cooperative Oncology Group performance status 0-1
• Adequate organ function as measured by: WBC ≥ 3.0 x 109/L, platelets ≥ 100 x 109/L, absolute neutrophil count \> 1.5 x 109/L, Hemoglobin (Hb) \> 5 mmol/L (\>8.1 g/dL), eGFR ≥ 35 ml/min, Serum transaminases (AST \& ALT) ≤ 5 x upper limit of normal (ULN), Total bilirubin ≤ ULN, Albumin \> 3 g/dL
• At least one measurable liver lesion according to the PERCIST 1.0

You may not qualify if:

• Significant extrahepatic disease, defined as symptomatic extrahepatic disease, more than 10 pulmonary nodules (maximum diameter of each lung metastasis \<20mm), and/or peritoneal carcinomatosis.
• Eligible for ablative local treatment of liver metastases (e.g. surgical resection, ablation)
• Lung shunt \>20 Gy, as calculated using scout dose SPECT/CT
• Absorbed tumor dose \<90 Gy when dosing at a maximum average absorbed normal liver dose
• Other malignancy confounding prognosis
• Receipt of chemotherapy within 28 days prior to study treatment
• Previous or current treatment with radioembolization
• Major surgery within 28 days or incompletely healed surgical incision before starting study therapy
• Any serious comorbidity preventing the safe administration of anti-VEGF antibody treatment. This includes uncontrolled hypertension or treatment with ≥3 antihypertensive drugs, arterial (cerebro)vascular event within the past 6 months, history of severe bleeding, history of GI perforation, or presence of fistulae
• Any serious and/or chronic liver disease preventing the safe administration of radio- embolization
• Uncorrectable extrahepatic deposition of scout dose activity; activity in the falciform ligament, portal lymph nodes and gallbladder is accepted
• Pregnancy or breastfeeding
• Body weight over 150 kg (because of maximum table load)
• Known severe allergy for intravenous contrast fluids
• Participation to another investigational study which may compromise any endpoint of the study

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (1)

UMC Utrecht

Utrecht, 3584CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Guus Bol, dr.

CONTACT

+31 88 75 652 43; G.M.Bol-2@umcutrecht.nl

Dania Al-Toma, drs.

CONTACT

D.Al-Toma-2@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: August 21, 2024
• Study Start: June 18, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: August 21, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)