RECRUITING

Botensilimab Plus Balstilimab and Fasting Mimicking Diet Plus Vitamin C for Patients with KRAS-Mutant Metastatic Colorectal Cancer

Conditions

Metastatic Colorectal Adenocarcinoma Stage IV Colorectal Cancer AJCC V8

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase Ib Study of Botensilimab Plus Balstilimab and Fasting-Mimicking Diet (FMD) Plus Vitamin C in Patients with KRAS-Mutant Metastatic Colorectal Cancer

Quick Facts

Study Start:2025-01-15

Study Completion:2028-01-15

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06336902

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * 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.	* Patients with a current diagnosis of diabetes mellitus are not eligible for this study. * 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. * 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). * 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

Inclusion Criteria

Exclusion 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.
* 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.

* Patients with a current diagnosis of diabetes mellitus are not eligible for this study.
* 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.
* 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).
* 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

Contacts and Locations

Study Contact

Charlean Ketchens, RN

CONTACT

323-865-0451

Charlean.Ketchens@med.usc.edu

Rabia Rehman

CONTACT

323-865-0451

Rabia.Rehman@med.usc.edu

Principal Investigator

Diana Hanna, MD

PRINCIPAL_INVESTIGATOR

University of Southern California

Study Locations (Sites)

Los Angeles General Medical Center

Los Angeles, California, 90033

United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033

United States

Collaborators and Investigators

Sponsor: University of Southern California

Diana Hanna, MD, PRINCIPAL_INVESTIGATOR, University of Southern California

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-01-15

Study Completion Date2028-01-15

Study Record Updates

Study Start Date2025-01-15

Study Completion Date2028-01-15

Terms related to this study

Additional Relevant MeSH Terms

Metastatic Colorectal Adenocarcinoma
Stage IV Colorectal Cancer AJCC V8