Trial Title:
Botensilimab Plus Balstilimab and Fasting Mimicking Diet Plus Vitamin C for Patients With KRAS-Mutant Metastatic Colorectal Cancer
NCT ID:
NCT06336902
Condition:
Metastatic Colorectal Adenocarcinoma
Stage IV Colorectal Cancer AJCC v8
Conditions: Official terms:
Colorectal Neoplasms
Study type:
Interventional
Study phase:
Phase 1
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:
Biological
Intervention name:
Balstilimab
Description:
Given IV
Arm group label:
Treatment (botensilimab, balstilimab, FMD, vitamin C)
Other name:
AGEN 2034
Other name:
AGEN-2034
Other name:
AGEN2034
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (botensilimab, balstilimab, FMD, vitamin C)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Biological
Intervention name:
Botensilimab
Description:
Given IV
Arm group label:
Treatment (botensilimab, balstilimab, FMD, vitamin C)
Other name:
AGEN 1181
Other name:
AGEN-1181
Other name:
AGEN1181
Other name:
Anti-CTLA-4 Monoclonal Antibody AGEN1181
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (botensilimab, balstilimab, FMD, vitamin C)
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:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Other
Intervention name:
Dietary Intervention
Description:
Undergo FMD
Arm group label:
Treatment (botensilimab, balstilimab, FMD, vitamin C)
Other name:
Dietary Modification
Other name:
intervention, dietary
Other name:
Nutrition Intervention
Other name:
Nutrition Interventions
Other name:
Nutritional Interventions
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (botensilimab, balstilimab, FMD, vitamin C)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
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:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Dietary Supplement
Intervention name:
Vitamin C
Description:
Given IV
Arm group label:
Treatment (botensilimab, balstilimab, FMD, vitamin C)
Summary:
This phase Ib trial tests the safety, side effects, and effectiveness of botensilimab,
and balstilimab in combination with a fasting mimicking diet and high dose vitamin C in
treating patients with KRAS-mutant metastatic colorectal cancer. Botensilimab and
balstilimab are monoclonal antibodies that may interfere with the ability of tumor cells
to grow and spread. KRAS is protein found on some tumor cells that is involved in the
growth of tumor cells. KRAS mutant cells have been found to be more sensitive to vitamin
C induced growth suppression in the presence of low-sugar (glucose). A fasting mimicking
diet, a plant-based, calorie reduced, low-sugar diet alternating with refeeding periods,
may positively change the way the body responds to cancer treatment. Vitamin C is a
nutrient that the body needs in small amounts to function and stay healthy. It is an
antioxidant that that can help prevent cell damage and may block growth and spread of
tumor cells. Botensilimab and balstilimab in combination with a fasting mimicking diet
and high dose vitamin C may be safe, tolerable and effective in treating patients with
KRAS-mutant metastatic colorectal cancer.
Detailed description:
PRIMARY OBJECTIVES:
I. To evaluate the feasibility of the fasting mimicking diet (FMD) when combined with
vitamin C and botensilimab plus balstilimab by determining the proportion of patients who
adhere to the FMD ≥ 75% of the designated days and receive all doses of botensilimab,
balstilimab and Vitamin C for at least any two cycles of therapy.
II. To characterize the safety and tolerability of FMD and vitamin C when combined with
botensilimab and balstilimab by assessing any grade toxicities per Common Terminology
Criteria for Adverse Events (CTCAE) 5.0.
SECONDARY OBJECTIVES:
I. To obtain a preliminary assessment of anti-tumor activity of botensilimab plus
balstilimab and FMD plus vitamin C by determining the overall response rate using
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
II. To estimate the progression-free and overall survival in patients with KRAS-mutant
colorectal cancer (CRC) receiving botensilimab plus balstilimab and FMD plus vitamin C.
EXPLORATORY OBJECTIVES:
I. To characterize circulating tumor deoxyribonucleic acid (ctDNA) and ctDNA methylation
(TET, Wnt, JAK/STAT, PI3K/AKT, CXCR, ALDH, AMPK) profiles at baseline, on treatment and
at disease progression.
II. To examine metabolomic markers (IGF-1, GAPDH, DHA, GLUT-1, iron signaling) at
baseline, on treatment and at disease progression.
OUTLINE:
Patients receive botensilimab intravenously (IV) over 30 minutes on day 1 of each cycle
for up to 4 cycles. Patients receive balstilimab IV over 30 minutes and vitamin C IV over
30 minutes on days 1, 15 and 29 of each cycle. Patients undergo a FMD on days -4 to -1 of
each cycle. Cycles repeat every 42 days for up to 2 years in the absence of disease
progression or unacceptable toxicity. Additionally, patients undergo blood sample
collection, computed tomography (CT) scans and magnetic resonance imaging (MRI)
throughout the study.
After completion of study intervention, patients are followed up at 30 days and every 3
months for up to 6 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically or cytologically confirmed microsatellite stable (MSS) metastatic
colorectal adenocarcinoma with any KRAS mutation (as determined by a Clinical
Laboratory Improvement Act [CLIA]-certified lab), including metastases to liver,
lung, etc.
- Disease progression, intolerance or contraindication to a fluoropyrimidine,
oxaliplatin, irinotecan
- ≥ 18 years of age
- Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
- Estimated life expectancy ≥ 3 months
- Body mass index (BMI) ≥ 18.5
- Absolute neutrophil count ≥ 1,500/mcL
- Hemoglobin ≥ 8.0 g/dL
- Platelets ≥ 75,000/mcL
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (for patients with Gilbert
syndrome ≤ 3.0 x ULN)
- Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 x ULN
- Creatinine ≤ 1.5 x ULN
- Measurable disease as defined by RECIST 1.1
- No history of prior or current malignancy that requires active treatment
- Female patients of childbearing potential must be willing to use highly effective
contraceptive measures starting with the Screening visit through 90 days after last
dose of study treatment.
Note: Abstinence is acceptable if this is the established and preferred contraception for
the patient
- Female patients of childbearing potential must have a negative serum pregnancy test
at screening (within 72 hours of first dose of study medication). Non-childbearing
potential is defined as 1 of the following:
- ≥ 45 years of age and has not had menses for > 1 year
- Amenorrheic for > 2 years without a hysterectomy and/or oophorectomy and
follicle stimulating hormone value in the postmenopausal range upon pretrial
(screening) evaluation
- Status is post-hysterectomy, -oophorectomy, or -tubal ligation
- Male patients with a female partner(s) of childbearing potential must agree to use
highly effective contraceptive measures throughout the trial starting with the
Screening visit through 90 days after the last dose of study treatment is received.
Males with pregnant partners must agree to use a condom; no additional method of
contraception is required for the pregnant partner.
Note: Abstinence is acceptable if this is the established and preferred contraception for
the patient
Exclusion Criteria:
- Patients with a current diagnosis of diabetes mellitus are not eligible for this
study.
Note: Patients with pre-diabetes or previous diabetes or glucose intolerance and who are
currently not taking any diabetes medications are eligible
- Patients taking medications that cannot be safely stopped during the fasting periods
or which may not be safely taken without food are not eligible for this study
- Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or
major surgery within 3 weeks prior to first dose of study drug. A 1-week washout is
permitted for palliative radiation to non-central nervous system (CNS) disease, with
approval from the principal investigator
- History of syncope with caloric restriction or another medical comorbidity which
would make fasting potentially dangerous
- Current use of oral vitamin C supplements
- Currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigation
device within 3 weeks of first dose of current study drug
- Expected to require any other form of systemic or localized antineoplastic therapy
while on trial (including maintenance therapy with another agent, radiation therapy,
and/or surgical resection)
- History of anti-PD1 or anti-CTLA4 therapy
- Unresolved toxicity ≥ CTCAE grade 2 except for neuropathy, alopecia
- Untreated brain or leptomeningeal metastases or previously treated CNS metastases
with any of the following: residual neurologic deficit; history of seizures; ongoing
requirement of steroids, exceeding prednisone 10 mg daily dose
- Patients who have uncontrolled or severe hyponatremia, hypernatremia, syndrome of
inappropriate antidiuretic hormone secretion (SIADH), hypokalemia, hyperkalemia,
hypomagnesemia, or hypermagnesemia
- Patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary
spherocytosis, or other conditions predisposing patient to hemolysis
- Patients who have a history of oxalate renal calculi
- Major surgery within 4 weeks of first dose of immunotherapy
- Known severe (grade ≥ 3) hypersensitivity reactions to fully human monoclonal
antibodies, antibody, or severe reaction to immuno-oncology agents, such as colitis
or pneumonitis requiring treatment with steroids; or has a history of interstitial
lung disease, any history of anaphylaxis, or uncontrolled asthma
- Evidence of bleeding diathesis or clinically significant coagulopathy
- Receiving systemic corticosteroid therapy 1 week prior to the first dose of study
drug or receiving any other form of systemic immunosuppressive medication.
Note: Corticosteroid use as a premedication for IV contrast allergies/reactions is
allowed. Patients who are receiving daily corticosteroid replacement therapy are also an
exception to this rule. Daily prednisone at doses of ≤ 10 mg or equivalent hydrocortisone
dose are examples of permitted replacement therapy. Use of inhaled or topical
corticosteroid is permitted
- Active or history of autoimmune disease that requires systemic treatment within 2
years of the start of study drug (i.e., use of disease-modifying agents,
corticosteroids, or immunosuppressive drugs).
Note: Patients with autoimmune conditions requiring hormone replacement therapy or
topical treatments are eligible
- Has had an allogeneic tissue/solid organ transplant, except for corneal transplants
- Legally incapacitated or has limited legal capacity
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, active coronary artery disease,
myocardial infarction or cerebrovascular accident within 6 months prior to study
entry, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Los Angeles General Medical Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Contact:
Last name:
Charlean Ketchens, RN
Phone:
323-865-0451
Email:
Charlean.Ketchens@med.usc.edu
Contact backup:
Last name:
Rabia Rehman
Phone:
323-865-0451
Email:
Rabia.Rehman@med.usc.edu
Investigator:
Last name:
Diana Hanna, MD
Email:
Principal Investigator
Facility:
Name:
USC / Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Contact:
Last name:
Charlean Ketchens, RN
Phone:
323-865-0451
Email:
Charlean.Ketchens@med.usc.edu
Contact backup:
Last name:
Rabia Rehman
Phone:
323-865-0451
Email:
Rabia.Rehman@med.usc.edu
Investigator:
Last name:
Diana Hanna, MD
Email:
Principal Investigator
Start date:
October 1, 2024
Completion date:
October 1, 2027
Lead sponsor:
Agency:
University of Southern California
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
University of Southern California
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06336902
