Clinical trial NCT06563986: FTD-TPI, Bevacizumab, and Radioembolization With 166Ho-microspheres in Refractory Metastatic Colorectal Cancer
Official title: Single-arm, Phase II Trial of Trifluridine/Tipiracil (FTD-TPI), Bevacizumab, and Individualized Radioembolization With 166Ho-microspheres in Refractory Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Radioembolization
Trifluridine/Tipiracil
Refractory Metastatic Colorectal Cancer
Radioembolization With 166Ho-microspheres
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2024-08-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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  * Patients who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Hepatic objective response rate (hORR) (PERCIST 1.0)
timeFrame: 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:
measure: Hepatic objective response rate (hORR) (RECIST 1.1)
timeFrame: Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.
measure: Overall and extra-hepatic ORR (RECIST 1.1)
timeFrame: Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.
measure: Overall and extra-hepatic ORR (PERCIST 1.0)
timeFrame: Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.
measure: Serious adverse events (SAE's)
timeFrame: 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.
measure: Grade ≥3 adverse events (CTCAE 5.0)
timeFrame: 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.
measure: Occurrence of radioembolization-induced liver disease (REILD)
timeFrame: Evaluated every 8 weeks after start treatment during the first half year.
measure: Radioembolization related vascular events
timeFrame: Evaluated every 8 weeks after start treatment during the first half year.
measure: Dose reductions, dose delays of FTD-TPI
timeFrame: Evaluated during the first two cycles (each cycle is 28 days).
measure: Radioembolization completion rate
timeFrame: Evaluated immediately after the radioembolization treatment.
measure: Progression free survival (PFS)
timeFrame: Evaluated every 8 weeks after the start of treatment until 1 year after the start of treatment or until disease progression, whichever comes first.
measure: Overall survival (OS)
timeFrame: Evaluated once per year until the end of the study (the end of study is defined as six months after the first day of the first treatment cycle (each cycle is 28 days) of the 36th evaluable participant).
Other outcomes:
measure: Dosimetry scout + post treatment 1 and 2
timeFrame: Evaluated immediately after the radioembolization treatment.
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
References: