To determine safety, tolerability, and activity of individualized radioembolization with 166Ho-microspheres combined with FTD-TPI and bevacizumab.
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess activity of radioembolization, FTD-TPI, and bevacizumab in terms of
hepatic objective tumor response (hORR) determined by PERCIST 1.0
Secondary outcome
Activity
• Hepatic objective response rate (hORR) (RECIST 1.1)
• Overall and extra-hepatic ORR (RECIST 1.1, PERCIST 1.0)
Safety
• SAE*s
• Grade >=3 adverse events (CTCAE 5.0)
• Occurrence of REILD (see 8.1.2)
• Radioembolization related vascular events
Tolerability
• Dose reductions, dose delays of FTD-TPI
• Radioembolization completion rate
Efficacy
• Progression-free survival
• Overall survival
Background 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.(Prager et al., 2023)
There is no clear treatment preference, therefore individual treatment goals
dictate the choice of extra-hepatic tumor stabilization with FTD-TPI and
bevacizumab or intra-hepatic tumor reduction with radioembolization. However,
in most patients with liver-dominant, chemotherapy-refractory mCRC both
treatment goals overlap. The combination of radioembolization, FTD-TPI, and
bevacizumab could potentially be preferable, if this is a safe and effective
alternative.
Study objective
To determine safety, tolerability, and activity of individualized
radioembolization with 166Ho-microspheres combined with FTD-TPI and
bevacizumab.
Study design
Single-arm, open label, phase II trial.
Intervention
• Individualized 166Ho radioembolization combined with:
• 35 mg/m2 FTD-TPI day 1-5 and 8-12, every 4 weeks
• 5 mg/kg bevacizumab iv. on day 1 and 15, every 4 weeks
Study burden and risks
It is hypothesized that systemic therapy and radioembolization improve hepatic
objective response rate of mCRC patients with liver dominant metastases
compared to the current standard treatment of systemic therapy alone. This
potential benefit should be weighed against the burden and risks of the
experimental treatment. The most important potential burden/risks are:
additional hospital visits, a small but increased risk for complications and an
intensified and prolonged initial treatment that could decrease health-related
quality of life. Taken into the account the severity of impact and likelihood
of occurrence of the potential risks, the investigators have classified this
study as medium risk. The investigators feel that the potential response rate
benefit of the experimental arm outweighs the burden and risks of
participation.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
• Unresectable liver dominant mCRC
• Prior therapy with fluoropyrimidine, oxaliplatin, and irinotecan for the
treatment of advanced colorectal cancer and had demonstrated progressive
disease or intolerance to their last regimen
• Written informed consent
• Age >=18 years
• Estimated hepatic tumor replacement >= 10% and <= 50% of total liver volume
• ECOG performance status 0-1
• Adequate organ function as measured by:
o WBC >= 3.0 x 109/L, platelets >= 100 x 109/L, absolute neutrophil count > 1.5 x
109/L, Hemoglobin > 5 mmol/L (>8.1 g/dL)
o eGFR >= 35 ml/min
o Serum transaminases (AST & ALT) <= 5 x ULN
o Total bilirubin <= ULN
o Albumin > 3 g/dL
• At least one measurable liver lesion according to the PERCIST 1.0
• Included in PLCRC
Exclusion criteria
• Significant extrahepatic disease, defined as symptomatic extrahepatic
disease, greater than 10 pulmonary nodules (maximum diameter of each lung
metastasis <20mm), and/or peritoneal carcinomatosis. (Definition of liver
dominant disease)(Fidelman et al., 2022)
• Eligible for 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 radioembolization
• 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL85987.041.24 |