Botensilimab Plus Balstilimab and Fasting Mimicking Diet Plus Vitamin C for Patients With KRAS-Mutant Metastatic Colorectal Cancer
A Phase Ib Study of Botensilimab Plus Balstilimab and Fasting-Mimicking Diet (FMD) Plus Vitamin C in Patients With KRAS-Mutant Metastatic Colorectal Cancer
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Time periods mentioned: 2 years, 6 months
- Procedures mentioned: Blood draws, MRI scans, CT scans
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "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."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests botensilimab and balstilimab with high-dose vitamin C and a plant-based diet that cuts calories and sugar during set periods. It checks safety, side effects, and how well the treatment works. It is for adults with colon or rectal cancer that has spread and has a KRAS gene change.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Age 18 or older.
- Tests confirm colon or rectal cancer that has spread, has a KRAS gene change, and is microsatellite stable (MSS), a type of tumor test result.
- Cancer worsened with fluoropyrimidine, oxaliplatin, and irinotecan, or these drugs caused problems or are not safe for you.
- Able to do most daily activities, with an expected life span of at least 3 months.
- Body mass index (BMI), a measure of weight compared with height, is at least 18.5.
- Blood cell counts and liver and kidney tests meet the study's limits.
- Cancer can be measured on scans. No other past or current cancer needs active treatment.
- Follow the study's pregnancy testing and birth control rules, including birth control through 90 days after the last dose when required.
Who can't join
- Current diabetes. People with prediabetes or past diabetes or blood sugar problems may qualify if they take no diabetes medicine.
- Fasting could be unsafe because of health problems, past fainting when eating less, or medicines that cannot safely be stopped or taken without food. Current vitamin C pills are also not allowed.
- Recent cancer treatment, major surgery, or another study treatment or device; need for other cancer treatment during this study; or past anti-PD1 or anti-CTLA4 immune treatment.
- Ongoing moderate or worse treatment side effects, except nerve damage or hair loss. Untreated cancer in the brain or its lining, or treated brain cancer with lasting nerve problems, seizures, or a need for higher-dose steroids.
- Severe or uncontrolled blood salt problems; conditions that cause red blood cells to break down, such as G6PD deficiency; past oxalate kidney stones; or serious bleeding or clotting problems.
- Past severe reactions to antibody or immune treatments, a severe allergic reaction called anaphylaxis, lung scarring disease, or uncontrolled asthma.
- Certain recent medicines that weaken the immune system, autoimmune disease needing whole-body treatment within 2 years, or a donor tissue or organ transplant other than a cornea transplant. Some steroid and hormone treatments are allowed.
- Uncontrolled illness, such as infection or serious heart disease; heart attack or stroke within 6 months; limited legal ability to consent; or mental health or social problems that prevent following study rules.
Simplified for readability. The official criteria below are what the study team uses.
Official 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
Study sites (3)
CA
- Saint Jude Medical Center / Providence Medical Foundation · Fullerton, CA 92835Maria Diosdado · Study contact · 714-446-5615 · Maria.Diosdado@providence.orgDavid Park, MD · Principal investigatorMore trials in Fullerton
- Los Angeles General Medical Center · Los Angeles, CA 90033Charlean Ketchens, RN · Study contact · 323-865-0451 · Charlean.Ketchens@med.usc.eduRabia Rehman · Study contact · 323-865-0451 · Rabia.Rehman@med.usc.eduDiana Hanna, MD · Principal investigatorMore trials in Los Angeles
- USC / Norris Comprehensive Cancer Center · Los Angeles, CA 90033Charlean Ketchens, RN · Study contact · 323-865-0451 · Charlean.Ketchens@med.usc.eduRabia Rehman · Study contact · 323-865-0451 · Rabia.Rehman@med.usc.eduDiana Hanna, MD · Principal investigatorMore trials in Los Angeles