Trial Title:
Y-90, Capecitabine, and Atezolizumab for Oligometastatic CRC
NCT ID:
NCT06555133
Condition:
Colorectal Carcinoma Metastatic in the Liver
Conditions: Official terms:
Colorectal Neoplasms
Capecitabine
Atezolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Combination Product
Intervention name:
yttrium-90 radioembolization
Description:
yttrium-90 radioembolization in combination with capecitabine and atezolizumab for the
treatment of unresectable colorectal cancer liver metastases in individuals who have been
treated with two or more lines of systemic therapy.
Arm group label:
yttriuM-90 in combination with capEcitabine and aTezolizumab
Other name:
capecitabine and atezolizumab
Summary:
BrUOG-430 is a prospective, single-arm, phase 2 trial evaluating yttrium-90
radioembolization in combination with capecitabine and atezolizumab for the treatment of
unresectable colorectal cancer liver metastases in individuals who have been treated with
two or more lines of systemic therapy.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed diagnosis of colorectal adenocarcinoma
2. Surgically unresectable, liver-isolated or liver-dominant, RECIST measurable,
metastatic disease
3. Age ≥18 years at the time of signing informed consent
4. ECOG performance status 0 or 1
5. Progression on 2 or more lines of systemic therapy
6. Agreeable to providing tumor tissue and blood for exploratory correlative analyses
7. Less than 50% of liver volume replaced by metastatic disease (as determined by
investigator)
8. Demonstrate adequate organ function as defined in table below (all screening labs
should be performed within 14 days of atezolizumab initiation):
Hematologic Absolute neutrophil count (ANC) ≥1,500 /mcL or ≥1,200 /mcL for those
with benign ethnic neutropenia Absolute Lymphocyte Count (ALC) ≥ 0.5 x 109/L
(500/uL) Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L within 7 days of
assessment. Patient may be transfused or receive EPO to meet this criterion
Renal Serum creatinine OR measured or calculated creatinine clearance ≤1.5 X upper
limit of normal (ULN) OR (GFR can also be used in place of creatinine or CrCl) ≥60
mL/min for subject with creatinine levels > 1.5 X institutional ULN
Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects
with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 5 X ULN Alkaline
Phosphatase ≤ 5 X ULN Albumin ≥2.5 mg/dL
Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated
Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving
anticoagulant therapy. For patients receiving therapeutic anticoagulation: stable
anticoagulant regimen
≤1.5 X ULN unless subject is receiving anticoagulant therapy. For patients receiving
therapeutic anticoagulation: stable anticoagulant regimen
Creatinine clearance should be calculated per institutional standard. Exceptions can
be made for patients with known Gilbert disease (≤ 3X ULN)
9. Female subjects of childbearing potential must be willing to use an adequate method
of contraception from the time of the negative pregnancy test until a minimum of 6
months after the last dose of study drug. Effective forms of contraception include
abstinence, hormonal contraceptive (injectable or implantable), or intrauterine
device in conjunction with a barrier method. Breast feeding subjects must be willing
to discontinue at treatment start and for 5 months post-treatment.
10. Male subjects of childbearing potential must agree to use an adequate method of
contraception with female partners of childbearing potential including abstinence or
condoms plus an additional contraceptive method such as hormonal contraceptive
(injectable or implantable), or intrauterine device during the study and for up to 3
months after the last dose of study drug.
11. Ability to understand and the willingness to sign a written informed consent
document and to comply with the study protocol procedures
Exclusion Criteria:
1. Prior yttrium-90 therapy
2. Prior external beam radiation therapy to the liver
3. Predicted life expectancy of less than 3 months
4. Known mismatch repair deficiency (dMMR), microsatellite instability (MSI-H), or high
tumor mutational burden (TMB-H) defined as ≥ 10 mutations per megabase
5. Known metastasis to the peritoneum or central nervous system. Exceptions include
subjects with untreated brain metastases ≤ 1 cm, if asymptomatic and not requiring
immediate radiation or steroids, and subjects with brain metastases that are treated
and stable for 1 month
6. Treatment with investigational therapy within the 28 days of initiation of study
treatment
7. Systemic treatment within 14 days or 5 half-lives of the drug (whichever is longer)
prior to initiation of study treatment
8. Prior treatment with CD137 agonists or anti-PD1, anti-PD-L1, anti-CTLA4 antibodies
9. A history of or current evidence of any condition (e.g. known deficiency of the
enzyme dihydropyrimidine dehydrogenase [DPD]), therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator
10. Known New York Heart Association class 3/4 congestive heart failure, left
ventricular ejection fraction <40% (if previously measured), myocardial infarction
within 6 months prior to enrollment, unstable angina, or unstable arrhythmia
11. Chronic obstructive pulmonary disease (COPD) requiring oral corticosteroids or
chronic oxygen
12. History of autoimmune disease, including, but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, idiopathic pulmonary fibrosis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
syndrome, granulomatosis with polyangiitis, Guillain-Barré syndrome, multiple
sclerosis, vasculitis, or glomerulonephritis, with the exception of: hypothyroidism
(on stable dose of thyroid replacement therapy), asthma managed with inhaled
medications only; type 1 diabetes mellitus on stable insulin regimen, Sjögren
syndrome, immune thrombocytopenia or autoimmune hemolytic anemia that does not
require systemic therapy; dermatologic condition (including eczema, psoriasis,
lichen simplex chronicus, or vitiligo) with skin manifestations with rash covering
<10% of body surface area and not requiring treatment other than low-potency topical
corticosteroids for >12 months prior to registration
13. Treatment with systemic immunosuppressive medication (including, but not limited to,
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or
anticipation of need for systemic immunosuppressive medication during study
treatment, with the following exceptions:
- Patients who received acute, low-dose systemic immunosuppressant medication or
a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours
of corticosteroids for a contrast allergy) are eligible for the study.
- Patients who received mineralocorticoids (e.g., fludrocortisone),
corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or
low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency
are eligible for the study.
14. Positive for HIV at screening or any time prior to screening: patients without prior
positive HIV test result will undergo an HIV test at screening, unless not permitted
under local regulations
15. Active Hepatitis B virus (HBV) infection (chronic or acute): defined as having a
positive hepatitis B surface antigen (HBsAg) test at screening. Patients with a past
or resolved HBV infection, defined as having a negative HBsAg test and a positive
total hepatitis B core antibody test at screening, are eligible for the study
16. Active hepatitis C virus (HCV) infection: defined as positive HCV antibody test
followed by a positive HCV RNA test at screening. The HCV RNA test will be performed
only for patients who have a positive HCV antibody test
17. Active TB (Mycobacterium tuberculosis)
18. Administration of a live, attenuated vaccine within 28 days before first
atezolizumab dose or anticipation that such a live, attenuated vaccine will be
required during the study or within 5 months after the final dose of atezolizumab
19. History of severe allergic anaphylactic reactions to chimeric or humanized
antibodies. Known hypersensitivity to Chinese hamster ovary cell products or to any
component of the atezolizumab formulation
20. Inability to swallow medication
21. History of other malignancy that could affect compliance with the protocol or
interpretation of results; patients with a curatively treated skin cancer, in situ
cervical cancer, or non-CRC malignancy are eligible if the non-CRC malignancy is
controlled and will not interfere with measurement of treatment efficacy or safety
22. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) at study enrollment or any major episode
of infection requiring treatment with IV antibiotics or hospitalization within 28
days before the first dose of atezolizumab.
23. Any major surgery or significant traumatic injury within 28 days of initiating study
treatment or anticipation of need for a major surgical procedure during the study
24. Evidence of other significant or uncontrolled medical or psychiatric conditions that
could affect compliance with the protocol
25. Pregnancy, breast-feeding, or prisoner status
26. History of leptomeningeal disease
27. Uncontrolled tumor-related pain
28. Patients requiring pain medication must be on a stable regimen at study entry.
29. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement)
amenable to palliative radiotherapy should be treated prior to enrollment. Patients
should be recovered from the effects of radiation. There is no required minimum
recovery period.
Asymptomatic metastatic lesions that would likely cause functional deficits or
intractable pain with further growth (e.g., epidural metastasis that is not
currently associated with spinal cord compression) should be considered for
loco-regional therapy if appropriate prior to enrollment.
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently).
• Patients with indwelling catheters (e.g., PleurX) are allowed.
30. Uncontrolled or symptomatic hypercalcemia (ionized calcium 1.5 mmol/L, calcium 12
mg/dL or corrected serum calcium ULN)
31. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan.
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
32. Prior allogeneic stem cell or solid organ transplantation
33. Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may
affect the interpretation of the results, or may render the patient at high risk
from treatment complications
34. Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug
(whichever is longer) prior to initiation of study treatment
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
August 30, 2024
Completion date:
September 1, 2029
Lead sponsor:
Agency:
Brown University
Agency class:
Other
Collaborator:
Agency:
Sirtex Medical
Agency class:
Industry
Collaborator:
Agency:
Genentech, Inc.
Agency class:
Industry
Source:
Brown University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06555133
