Trial Title:
CBM588 Capsules in Combination With Nivolumab and Ipilimumab for the Treatment of Advanced Stage Kidney Cancer
NCT ID:
NCT06399419
Condition:
Advanced Clear Cell Renal Cell Carcinoma
Advanced Renal Cell Carcinoma
Advanced Sarcomatoid Renal Cell Carcinoma
Metastatic Clear Cell Renal Cell Carcinoma
Metastatic Renal Cell Carcinoma
Metastatic Sarcomatoid Renal Cell Carcinoma
Stage III Renal Cell Cancer AJCC v8
Stage IV Renal Cell Cancer AJCC v8
Conditions: Official terms:
Carcinoma
Carcinoma, Renal Cell
Nivolumab
Ipilimumab
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:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (CBM588 capsules, nivolumab, ipilimumab)
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 (CBM588 capsules, nivolumab, ipilimumab)
Other name:
Bone Scintigraphy
Intervention type:
Biological
Intervention name:
CBM588 Capsules
Description:
Given PO
Arm group label:
Treatment (CBM588 capsules, nivolumab, ipilimumab)
Other name:
CBM588
Other name:
Clostridium butyricum MIYAIRI 588
Other name:
C. butyricum MIYAIRI 588
Other name:
C. butyricum strain MIYAIRI 588
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (CBM588 capsules, nivolumab, ipilimumab)
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:
Biological
Intervention name:
Ipilimumab
Description:
Given IV
Arm group label:
Treatment (CBM588 capsules, nivolumab, ipilimumab)
Other name:
Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
Other name:
BMS-734016
Other name:
Ipilimumab Biosimilar CS1002
Other name:
MDX-010
Other name:
MDX-CTLA4
Other name:
Yervoy
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (CBM588 capsules, nivolumab, ipilimumab)
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:
Biological
Intervention name:
Nivolumab
Description:
Given IV
Arm group label:
Treatment (CBM588 capsules, nivolumab, ipilimumab)
Other name:
ABP 206
Other name:
BCD-263
Other name:
BMS-936558
Other name:
CMAB819
Other name:
MDX-1106
Other name:
NIVO
Other name:
Nivolumab Biosimilar ABP 206
Other name:
Nivolumab Biosimilar BCD-263
Other name:
Nivolumab Biosimilar CMAB819
Other name:
ONO-4538
Other name:
Opdivo
Summary:
This phase I trial tests the safety, side effects, best dose, and effectiveness of CBM588
in combination with nivolumab and ipilimumab in treating patients with kidney cancer that
may have spread from where it first started to nearby tissue, lymph nodes, or distant
parts of the body (advanced). CBM588 is a live biotherapeutic that may help improve the
effects of immunotherapy. Nivolumab and ipilimumab are monoclonal antibodies that may
interfere with the ability of tumor cells to grow and spread by enhancing the ability of
the body's immune cells to attack tumor cells. CBM588 in combination with nivolumab and
ipilimumab may be safe, tolerable, and/or effective in treating patients with advanced
stage kidney cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the safety and tolerability of nivolumab/ipilimumab with escalating doses
of Clostridium butyricum MIYAIRI 588 capsules (CBM588) in patients with metastatic renal
cell carcinoma.
SECONDARY OBJECTIVES:
I. To evaluate the effect of CBM588 on the clinical efficacy of nivolumab/ipilimumab.
II. To determine the effect of CBM588 (in combination with nivolumab/ipilimumab) in
modulation of the gut microbiome in patients with metastatic renal cell carcinoma.
III. To assess the effect of CBM588 on the change of metabolic pathways with the
nivolumab/ipilimumab combination in patients with metastatic renal cell carcinoma.
IV. To determine the effect of CBM588 on systemic immunomodulation.
OUTLINE: This is a dose-escalation study of CBM588 followed by a dose-expansion study.
Patients receive CBM588 capsules orally (PO) twice daily (BID) on days 1-21, nivolumab
intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each
cycle. Cycles repeat every 21 days for 4 cycles. Patients then receive CBM588 PO BID on
days 1-28 and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of
disease progression or unacceptable toxicity. Additionally, patients undergo computed
tomography (CT), bone scan and blood sample collection throughout the study. Patients may
optionally undergo magnetic resonance imaging (MRI) on study.
After completion of study treatment, patients are followed up once a year.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Documented informed consent of the participant and/or legally authorized
representative
- Assent, when appropriate, will be obtained per institutional guidelines
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- If unavailable, exceptions may be granted with study principle investigator
(PI) approval
- Eastern Cooperative Oncology Group (ECOG) ≤ 2
- Age ≥ 18 years
- Histologically confirmed renal cell carcinoma with clear cell renal cell carcinoma
component or sarcomatoid component
- Advanced (not amenable to curative surgery or radiation therapy) or metastatic
(American Joint Committee on Cancer [AJCC] stage IV) renal cell carcinoma with
intermediate- or poor-risk disease by International Metastatic Renal Cell Carcinoma
Database Consortium (IMDC) criteria
- No prior systemic therapy for renal cell carcinoma (RCC) with the following
exception:
- One prior adjuvant or neoadjuvant therapy for completely resectable RCC if
recurrence occurred at least 6 months after the last dose of adjuvant or
neoadjuvant therapy
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior
anti-cancer therapy
- Absolute neutrophil count (ANC) ≥ 1500/uL without granulocyte colony-stimulating
factor support
- White blood cell count ≥ 2500/uL
- Platelets ≥ 100,000/uL without transfusion
- Hemoglobin ≥ 8 g/dL
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline
phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN with documented
bone metastases
- Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN)
- Serum albumin ≥ 2.8 g/dl
- Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin
time (PTT) test < 1.3 x the laboratory ULN
- Serum calculated creatinine clearance ≥ 50mL/min using the Cockcroft-Gault equation
- Sexually active fertile subjects and their partners must agree to use medically
accepted methods of contraception (e.g., barrier methods, including male condom,
female condom, or diaphragm with spermicidal gel) during the course of the study and
for 5 months after the last dose of nivolumab for women with childbearing potential,
and 7 months after the last dose of nivolumab for men
- Female subjects of childbearing potential must not be pregnant at screening. Female
subjects are considered to be of childbearing potential unless one of the following
criteria is met: documented permanent sterilization (hysterectomy, bilateral
salpingectomy, or bilateral oophorectomy) or documented postmenopausal status
(defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of
other biological or physiological causes. In addition, females < 55 years-of-age
must have a serum follicle stimulating (FSH) level > 40 mIU/mL to confirm
menopause).
- Note: Documentation may include review of medical records, medical
examinations, or medical history interview by study site
Exclusion Criteria:
- Prior treatment with ipilimumab and/or nivolumab
- Current use, or intent to use, probiotics, yogurt, or bacterial fortified foods
during the period of treatment
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to study agent
- Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis
requiring treatment with systemic steroids
- Known medical condition (e.g., a condition associated with diarrhea or acute
diverticulitis) that, in the investigator's opinion, would increase the risk
associated with study participation or study drug administration or interfere with
the interpretation of safety results
- Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy
(including investigational) within 4 weeks before first dose of study treatment
- Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy
within 4 weeks before first dose of study treatment. Systemic treatment with
radionuclides within 6 weeks before first dose of study treatment. Subjects with
clinically relevant ongoing complications from prior radiation therapy are not
eligible
- Known brain metastases or cranial epidural disease unless adequately treated with
radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks
prior to first dose of study treatment after radiotherapy or at least 4 weeks prior
to first dose of study treatment after major surgery (e.g., removal or biopsy of
brain metastasis). Subjects must have complete wound healing from major surgery or
minor surgery before first dose of study treatment. Eligible subjects must be
neurologically asymptomatic and without corticosteroid treatment at the time of
first dose of study treatment
- Administration of a live, attenuated vaccine within 30 days before first dose of
study treatment
- The subject has uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions:
- Any condition requiring systemic treatment with either corticosteroids (> 10 mg
daily prednisone equivalent) or other immunosuppressive medications within 14
days before first dose of study treatment. Note: Inhaled, intranasal,
intra-articular, or topical steroids are permitted. Adrenal replacement steroid
doses ≤ 10 mg daily prednisone equivalent are permitted. Transient short-term
use of systemic corticosteroids for allergic conditions (e.g., contrast
allergy) is also allowed
- Active infection requiring systemic treatment. Acute or chronic hepatitis B or
C infection, known human immunodeficiency virus (HIV) or acquired
immunodeficiency syndrome (AIDS)-related illness requiring systemic treatments,
or known positive test for tuberculosis infection where there is clinical or
radiographic evidence of active mycobacterial infection
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on
screening chest CT scan
- Malabsorption syndrome
- Uncompensated/symptomatic hypothyroidism
- Moderate to severe hepatic impairment (Child-Pugh B or C)
- Requirement for hemodialysis or peritoneal dialysis
- History of solid organ or allogenic stem cell transplant
- Other clinically significant disorders that would preclude safe study
participation
- Any active, known, or suspected autoimmune disease will be excluded, with
the following exceptions:
- Type 1 diabetes mellitus
- Hypothyroidism only requiring hormone replacement
- Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring
systemic treatment
- Conditions not expected to recur in the absence of an external
trigger
- Pregnant or lactating females
- Inability to swallow tablets/capsules or unwillingness or inability to receive IV
administration
- Previously identified allergy or hypersensitivity to components of the study
treatment formulations or history of severe infusion-related reactions to monoclonal
antibodies. Subjects with rare hereditary problems of galactose intolerance, the
Lapp lactase deficiency or glucose-galactose malabsorption are also excluded
- Any other active malignancy at time of first dose of study treatment or diagnosis of
another malignancy within 3 years prior to first dose of study treatment that
requires active treatment, except for locally curable cancers that have been
apparently cured, such as basal or squamous cell skin cancer, superficial bladder
cancer, or carcinoma in situ of the prostate, cervix, or breast
- Exclusion of subjects with a history of myocarditis or congestive heart failure (as
defined by New York Heart Association Functional Classification III or IV), as well
as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection,
or myocardial infarction 6 months prior to study entry
- Exclusion of subjects whose baseline pulse oximetry is less than 92% on room air
- Any other condition that would, in the investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures
- Prospective participants who, in the opinion of the investigator, may not be able to
comply with all study procedures (including compliance issues related to
feasibility/logistics)
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:
Alex Chehrazi-Raffle, MD
Phone:
626-218-4772
Email:
achehraziraffle@coh.org
Investigator:
Last name:
Alex Chehrazi-Raffle, MD
Email:
Principal Investigator
Start date:
June 19, 2024
Completion date:
October 19, 2026
Lead sponsor:
Agency:
Osel, Inc.
Agency class:
Industry
Collaborator:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
Miyarisan Pharmaceuticals, Co., Ltd.
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Osel, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06399419
