This study has been transitioned to CTIS with ID 2024-514767-26-00 check the CTIS register for the current data. To find the maximum tolerated dose of glass yttrium-90 (90Y) microspheres (TheraSphere®), when combined with DEBIRI in patients with…
ID
Source
Brief title
Condition
- Metastases
- Hepatobiliary therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The maximum tolerated absorbed dose of 90Y-microspheres (TheraSphere®, BTG
international) when combined with DEBIRI for liver dominant mCRC.
Secondary outcome
Secondary endpoints:
- Adverse events (AEs) and serious adverse events (SAEs), up to 2 months after
the second and final treatment cycle. AEs and SAEs are defined by the study
protocol (NCI Common Toxicity Criteria for Adverse Events; CTCAE v 5.0).
- Overall response rate (ORR, every 3 months up to progression) of the CRLM
from the first treatment cycle by RECIST v1.1 and PERCIST, according to index
lesions, hepatic response and overall response.
- Overall Survival (OS), evaluated 12 months after enrolment of the last
patient.
- Conversion from non-resectable to resectable CRLM.
- Tumor marker (CEA) at 2 months after the second and final treatment cycle
- Circulating tumor DNA levels before and after treatment.
- Amount of drug-eluting beads (DEB) delivered.
- Post-treatment dosimetry, related to pre-treatment dosimetry, as assessed by
Simplict90Y* software.
Background summary
Drug eluting beads preloaded with irinotecan (DEBIRI) is a promising method of
treating patients with liver-dominant metastatic colorectal carcinoma (mCRC),
and is a reimbursed procedure in several European countries. Although tumor
response is generally good after DEBIRI (68.6% overall response rate), all
patients eventually have progressive disease. A large proportion of those
patients has progression in the liver (54%). Another increasingly used
minimally invasive treatment for patients with liver-dominant mCRC is
radioembolization, which irradiates tumors from the inside out.
Radioembolization has proven to prolong the time to progression. However,
almost all patients eventually have progressive disease, and an overall
survival benefit was not yet proven. Due to their differing mechanisms of
action, combining DEBIRI with radioembolization is expected to provide double
coverage and improve progression free survival, as well as overall outcome.
Study objective
This study has been transitioned to CTIS with ID 2024-514767-26-00 check the CTIS register for the current data.
To find the maximum tolerated dose of glass yttrium-90 (90Y) microspheres
(TheraSphere®), when combined with DEBIRI in patients with liver-dominant
colorectal liver metastases (CRLM).
Study design
Phase I dose-escalation study.
Intervention
Injection of escalating doses of 90Y-microspheres followed by DEBIRI via a
catheter in the hepatic arteries.
Study burden and risks
Anticipation of benefits:
We expect that patients treated with radioembolization and DEBIRI will have a
more effective treatment of the CRLM compared to i.v. chemotherapy alone. This
may lead to a prolonged progression free survival and a better QoL. We also
expect the incidence and severity of systemic side effects of irinotecan to be
lower in DEBIRI compared to intravenous irinotecan based regimens.
Anticipation of the risks:
The risks associated with participation in this study mainly consist of the
side-effects of the individual treatments, and the combination of both. The
added risk of the combination lies in the fact that we have to find the maximum
tolerated dose. As both radioembolization and DEBIRI have hepatotoxic effects,
dose limiting toxicity (DLT) is expected to occur at some point during this
study. Hepatotoxicity must be treated symptomatically as radioembolization and
DEBIRI are permanent devices.
Side effects of radioembolization and DEBIRI
The most important side-effects related to radioembolization and DEBIRI
include:
• Post-embolization syndrome (PES) is a common side effect of both
radioembolization and DEBIRI, its symptoms include nausea, fever, right upper
quadrant pain, and increased liver enzymes. PES is generally well tolerated and
pain symptoms subside within 24 hours.
• Radioembolization-induced liver disease (REILD), occurs in 1-5% of
radioembolization cases and is a serious life-threatening side-effect. Improved
dosimetry and treatment planning aims to prevent this. Treatment is symptomatic
and mainly consists of high dose steroids.
Other side effects are with relatively low incidence or less significant
clinical impact are listed in the answer to question E9 or in paragraphs 6.4
and 7.4 of the protocol
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
1. Written informed consent.
2. >=18 years old with confirmed unresectable liver metastases from CRC
3. The primary tumor should be clinically stable.
4. Bilobar (to avoid bias in toxicity analysis), unresectable liver dominant
mCRC (i.e. up to 2 lesions limited to one extra-hepatic organ with a maximum
size of 1 cm and 2 cm for lymph nodes), with disease progression after first
line systemic treatment.
5. Eligible to receive second-line standard-of-care chemotherapy with an
irinotecan-based chemotherapy regimen.
6. Measurable (target) liver lesions on contrast-enhanced CT, according to
RECIST 1.1.
7. Contrast-enhanced CT and FDG-PET-CT maximum 4 weeks prior to enrolment.
8. Tumor replacement >= 5% and <= 50% of total liver volume.
9. Started the last cycle of the first line chemotherapy (without irinotecan)
at least 28 days prior to the initiation of second line chemotherapy under the
protocol.
10. Eastern Cooperative Oncology Group performance status 0-1.
11. Life expectancy of >= 12 weeks.
12. Hematologic function: WBC >= 3.0 x 10^9/L, platelets >= 100 x 10^9/L,
absolute neutrophil count ; 1.5 x 10^9/L, Hemoglobin; 5 mmol/L.
13. Adequate organ function as measured by:
o GFR >= 35 ml/min.
o Serum transaminases (AST; ALT) <= 5 x ULN.
o Total bilirubin <= 1 x ULN
o Albumin > 3 g/dL.
Exclusion criteria
1. History of hepatic encephalopathy.
2. Contraindications to angiography.
3. Known severe allergy or intolerance to contrast agents, that cannot be
managed medically.
4. Pulmonary insufficiency or clinically evident chronic obstructive pulmonary
disease.
5. Cirrhosis or portal hypertension.
6. Prior liver-directed therapy (i.e. EBRT, chemoembolization,
radioembolization, hepatic segmentectomies, radiofrequency ablation spanning >2
segments).
7. Treatment with VEGF inhibitors within 28 days prior to receiving 90Y glass
microspheres.
8. Prior intervention for, or compromise of, the Ampulla of Vater.
9. Presence of clinically evident ascites (trace ascites on imaging is
acceptable), or Child-Pugh score B/C.
10. Toxicities due to prior cancer therapy that have not resolved before the
initiation of study treatment, if the investigator determines that the
continuing complication will compromise the safe treatment of the patient.
11. Significant life-threatening extra-hepatic disease, including patients who
have unresolved diarrhea or serious unresolved infections (e.g. patients who
are known to be HIV positive or have acute HBV or HCV).
12. Contraindications to the planned second line standard-of-care chemotherapy
regimen.
13. Pregnancy and/or breastfeeding.
14. Patients suffering from psychic disorders that make a comprehensive
judgment impossible, such as psychosis, hallucinations and/or depression.
15. Patients who are declared incapacitated.
16. Participation in a clinical trial with an investigational therapy within 30
days prior to enrolment.
17. Any co-morbid disease or condition that would place the patient at undue
risk.
18. Contraindications to TACE (e.g. porto-systemic shunt, portal vein
thrombosis, hepatofugal blood flow, severe atherosclerosis precluding arterial
access).
19. Contraindications to irinotecan (concomitant use with St John*s wort).
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 |
|---|---|
| EU-CTR | CTIS2024-514767-26-00 |
| EudraCT | EUCTR2018-002940-97-NL |
| CCMO | NL66938.041.19 |