Trial Title:
Immune Response Activation for the Treatment of Unresectable Metastatic Colorectal Cancer or CEA Positive Metastatic Breast Cancer
NCT ID:
NCT06130826
Condition:
Breast Carcinoma
Colorectal Carcinoma
Conditions: Official terms:
Carcinoma
Colorectal Neoplasms
Breast Neoplasms
Immunomodulating Agents
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tissue biopsy
Arm group label:
Treatment (SBRT, M5A-IL2 ICK)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (SBRT, M5A-IL2 ICK)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Scan
Description:
Undergo bone scan
Arm group label:
Treatment (SBRT, M5A-IL2 ICK)
Other name:
Bone Scintigraphy
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT or PET/CT
Arm group label:
Treatment (SBRT, M5A-IL2 ICK)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Immunotherapy
Description:
Receive M5A-IL2 ICK SC
Arm group label:
Treatment (SBRT, M5A-IL2 ICK)
Other name:
Immunological
Other name:
Immunological Therapy
Other name:
Immunologically Directed Therapy
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (SBRT, M5A-IL2 ICK)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Treatment (SBRT, M5A-IL2 ICK)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Radiation
Intervention name:
Stereotactic Body Radiation Therapy
Description:
Undergo SBRT
Arm group label:
Treatment (SBRT, M5A-IL2 ICK)
Other name:
SABR
Other name:
SBRT
Other name:
Stereotactic Ablative Body Radiation Therapy
Summary:
This phase I trial studies the side effects and best dose of M5A-IL2 immunocytokine
(M5A-ICK) combined with stereotactic body radiation therapy (SBRT) and to see how well
they work in treating patients with colorectal cancer or xarcinoembryonic antigen (CEA)
positive breast cancer that cannot be removed by surgery (unresectable) or has spread
from where it first started (primary site) to other places in the body (metastatic).
Carcinoembryonic Antigen (CEA) is a protein that is present in most colorectal cancers
and in many other cancers, such as breast cancer, as well. SBRT uses special equipment to
position a patient and deliver radiation to tumors with high precision. This method may
kill tumor cells with fewer doses over a shorter period and cause less damage to normal
tissue. Cytokines are signaling proteins that help control inflammation in the body. They
allow the immune system to mount a defense if germs or cancer or other substances that
can make people sick enter the body. Interleukin-2 (IL-2) is a powerful cytokine able to
regulate the immune responses that are important for anticancer immunity. Immunocytokines
(also called antibody-cytokine fusion proteins) are small proteins that regulate the
activity of immune cells. The M5A-IL2 immunocytokine (M5A-ICK) combines the cancer
targeting features of the M5A antibody with the immune system regulation properties of
the cytokine IL-2. Giving M5A-ICK in combination with standard of care (SOC) SBRT may
work better in treating patients with unresectable metastatic colorectal cancer or CEA
positive metastatic breast cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. Identify the maximum tolerated dose (MTD) and recommend phase 2 dose (RP2D) and
characterize toxicities associated with administration of the M5A-IL2 after fractionated
SBRT.
SECONDARY OBJECTIVES:
I. Describe the therapeutic response to treatment of irradiated and unirradiated tumors
per Criteria in Solid Tumors version 1.1 (RECIST v 1.1) guidelines.
II. Describe AEs by M5A-IL2 dose level, per Common Terminology Criteria for Adverse
Events [CTCAE] version 5.0.
III. Describe the pharmacokinetics of M5A-IL2. IV. Describe the frequency of
auto-antibody formation, overall and by dose of M5A-IL2.
EXPLORATORY OBJECTIVE:
I. If medically feasible, tumors targeted for SBRT will be biopsied pre-SBRT and 1-2
weeks post 3rd dose of M5A-IL2.
OUTLINE: This is a dose-escalation study of M5A-ICK.
Patients undergo SOC SBRT over 3 fractions on days 1, 3, and 5, followed by M5A-ICK
subcutaneously (SC) on days 8, 9, and 10 once daily for a single cycle on study. Patients
undergo computed tomography (CT) or positron emission tomography (PET)/CT as well as
blood sample collection throughout the trial. Patients may undergo magnetic resonance
imaging or bone scan as clinically indicated on the trial. Additionally, patients may
optionally undergo tissue biopsy during screening and on study.
After completion of study treatment, patients are followed-up at 3 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients should have a diagnosis of metastatic colon or rectal or breast cancer that
is pathology proven
- Patients should have a CEA producing colorectal cancer or breast cancer defined as a
baseline CEA or prior documented CEA level exceeding 5 ng/ml or evidence of CEA
staining by Immunohistochemistry (IHC)
- Patients should 18 years of age or older
- Patients are willing and capable to consent to study and to adhere with all elements
of the study
- Patients who have failed to respond to standard systemic therapy, or for whom
standard or curative systemic therapy does not exist, is not tolerable or was
refused
- Patients should be at least 4 weeks from last receipt of a cytotoxic or biological
agent prior to start of SBRT, with the exception of mitomycin C which requires a
6-week washout
- Patients should have unresectable disease or not be a candidate for surgical
resection
- Patients must have a minimum of 1 and a maximum of 5 separate metastatic lesions
planned for SBRT. (Patients may have > 5 metastatic lesions overall, however only up
to 5 lesions will be treated with SBRT.) SBRT sites must be equal to or less than 5
cm in greatest dimension. SBRT treated sites must be measurable per RECIST 1.1 and
can include metastatic sites in the lung, liver, or soft tissue. Sites that are
intracranial or in the bone are excluded. Sites deemed not appropriate for SBRT by
the treating radiation oncologist are also excluded
- Patients should be at least 4 weeks from last radiation therapy prior to starting
SBRT
- Patients should be at least 4 weeks from any investigational therapy prior to
starting SBRT, with the exception of prior immunotherapy which would require a 3
month washout
- Patients should have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0-1
- Patients should be considered clinically stable with an estimated overall survival
of at least 3 months
- Neutrophil count > 1500/mm^3
- Lymphocyte count > 500/mm^3
- Hemoglobin > 9 gm/dl
- Platelets count > 100,000/mm^3
- Aspartate transaminase (AST)/alanine transaminase (ALT) < 2.5 x upper limit of
normal (ULN)
- Bilirubin ≤ ULN
- Patients should have adequate kidney function defined as a serum creatinine < ULN or
calculated creatinine clearance of > 60ml/min (Cockroft-Gault formula)
- Patients should have adequate cardiac function defined as:
- No history of acute coronary syndromes (including myocardial infarction,
unstable angina, Coronary artery bypass grafting (CABG), coronary angioplasty,
or stenting) < 12 months prior to screening
- No impaired cardiovascular function or clinically significant cardiovascular
diseases, including any of the following:
- Symptomatic chronic heart failure;
- Evidence of clinically significant cardiac arrhythmias and/or conduction
abnormalities
- No uncontrolled arterial hypertension despite appropriate medical therapy
(defined as systolic blood pressure > 160 or diastolic blood pressure >100)
- Electrocardiogram (EKG) showing normal sinus rhythm and a corrected QT (QTc) ≤
450 ms for male and ≤ 470 ms for female patients
- Patients should have adequate pulmonary function defined as:
- Lack of uncontrolled pleural effusion requiring recurrent draining procedures
(more than once per month)
- Lack of oxygen supplementation dependence
- All subjects must have the ability to understand and the willingness to sign a
written informed consent
- Screening 2-dimensional (2-D) echocardiogram (echo) shows a left ventricular
ejection fraction (LVEF) > 40%
- Urinalysis shows lack of proteinuria or a maximum of 1+ proteinuria
- Women of childbearing potential should use highly effective contraception while
receiving the trial regimen and for at least 5 half-lives of M5A-IL2 from the last
dose of M5A-IL2
Exclusion Criteria:
- Patients on immunosuppressive treatments including supra-physiological doses of
corticosteroids
- Patients with history of auto-immune disease including history of inflammatory bowel
disease
- Patients with active brain metastases
- Patients in the child-bearing ages who refuse to use adequate birth control measures
(example: contraceptives, barrier method, or abstinence)
- Lactating females who do not agree to stop breastfeeding
- Known active hepatitis B or C
- Major surgical procedure within 4 weeks prior to SBRT
- Non-healed wound or surgical incisions
- Radiographic evidence of bowel obstruction
- Electrolyte disturbances (sodium, potassium, magnesium, calcium, and phosphorous)
that are not correctable to at least CTCAE grade 1 with replacement therapy
- Known hypersensitivity of any of the study drug agents or components
- Patients should not have any uncontrolled illness including ongoing or active
infection
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to the study agents
- Pregnant women are excluded from this study because the investigational agents on
this study are highly likely to exert teratogenic or abortifacient effects
- Patients with other active malignancies are ineligible for this study
- Subjects, who in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jeffrey Y. Wong
Phone:
626-256-4673
Phone ext:
95200
Email:
jwong@coh.org
Investigator:
Last name:
Jeffrey Y. Wong
Email:
Principal Investigator
Start date:
November 12, 2024
Completion date:
September 5, 2026
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06130826
