Advanced Clear Cell Renal Cell CarcinomaPhase 3NCT07383441
Adding Biotherapy or Placebo to Standard Treatment for Advanced Kidney Cancer
A Phase 3 study testing Axitinib, Biospecimen Collection and Bone Scan in people with Advanced Clear Cell Renal Cell Carcinoma and Metastatic Clear Cell Renal Cell Carcinoma, run by SWOG Cancer Research Network at 41 sites in United States.
Trial summary
This phase III trial compares the effect of adding live biotherapy, MO-03, to standard of care (SOC) immunotherapy, including ipilimumab, nivolumab, axitinib, pembrolizumab, cabozantinib, and lenvatinib, to SOC immunotherapy alone in treating patients with clear cell renal cell cancer that may have spread from where… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Clear Cell Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8
- What is being tested?
- Axitinib, Biospecimen Collection and Bone Scan
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 718 participants
- Where
- 41 sitesUnited States
- Study dates
- 5 Jun 2026to 31 Jan 2034
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have histologically confirmed renal cell carcinoma (RCC) with clear cell component that is advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC at the time of registration on study
- Participants must have measurable/evaluable disease by RECIST 1.1 criteria. Participants with only bone metastases or only pleural effusions are considered evaluable disease and are eligible
- Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease must not require immediate central nervous system (CNS) specific treatment at the time of study registration or anticipated treatment during the first cycle of therapy
- Participants must not be currently enrolled or plan to participate in treatment studies while enrolled on this study
- Participants must not plan to take any over the counter probiotic supplements at time of study registration and while on protocol treatment
- NOTE: Vitamin and electrolyte or mineral supplements are permitted
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- Participants must not have had prior systemic therapy for advanced or metastatic RCC or any treatment with immune based combination therapy
- NOTE: Participants can have prior neo/adjuvant treatment with an anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 antibody or other therapies for any current or prior malignancy if > 12 months prior to registration
- Participants must not be receiving steroid replacement therapy for adrenal insufficiency greater than 50 mg daily of hydrocortisone or prednisone equivalent dose at the time of registration
- Participants must not require the use of systemic corticosteroids > 10 mg/day of prednisone or its equivalent for any reason other than replacement therapy for adrenal insufficiency
- Participants must not have received any systemic antibiotics within 7 days prior to registration
- NOTE: Uncontrolled infections must be completely resolved
- Participants must be ≥ 18 years old at the time of registration
- Participants must have a Zubrod performance status 0-2 within 28 days of registration
- Participants must be able to safely receive at least one of the standard of care regimens, per the current Food and Drug Administration (FDA)-approved package inserts, treating investigator's discretion, and institutional guidelines
- NOTE: Participants with favorable risk as defined by the International Metastatic RCC Database Consortium (IMDC) must plan to receive one of the TKI+ immunotherapy treatment combinations. They are not able to receive regimen 1 (ipilimumab + nivolumab) for this study
- Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications
- Participants must have serum creatinine ≤ 2 x ULN (upper limit of normal). This specimen must have been drawn and processed within 28 days prior to registration
- Hemoglobin ≥ 8 g/dL (within 28 days prior to registration)
- Leukocytes ≥ 3 x 10^3/uL (within 28 days prior to registration)
- Absolute neutrophil count ≥ 1.5 x 10^3/uL (within 28 days prior to registration)
- Platelets ≥ 100 x 10^3/uL (within 28 days prior to registration)
- Total bilirubin ≤ institutional upper limit of normal (ULN) unless history of Gilbert's disease (within 28 days prior to registration) Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional ULN (< 5 x institutional ULN if liver metastases are present) (within 28 days prior to registration)
- Participants must have alkaline phosphate measured as a part of the liver function assessment within 28 days prior to registration
- Participants must have albumin corrected calcium measured within 28 days prior to registration
- Participants with a history human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load on the most recent test results obtained within 6 months prior to registration
- Participants with a history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration
- Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration
- Participants must not have uncontrolled blood pressure and hypertension within 28 days prior to registration
- Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
- Participants must not have any known history of an autoimmune disease that prohibits the use of immune checkpoint therapy
- Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
- Participants must be offered the opportunity to participate in specimen banking
- Participants who have the ability to complete questionnaires in English or Spanish must be offered the opportunity to participate in the patient-reported outcome study
- NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
- Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
- For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
Who cannot join
None listed.
Trial locations and contacts
41 sites in 1 country. Contact the study team or a site near you to ask about taking part.
41 sites in 1 country
United States41 sites, 41 recruiting
- Recruiting
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org
Tareq Al baghdadi
- Recruiting
Lahey Hospital and Medical Center
Burlington, Massachusetts, 01805
Site Public Contact, 781-744-3421, lhmc-cancer-clinical-trials@lahey.org
Brendan Connell
- Recruiting
Illinois CancerCare-Canton
Canton, Illinois, 61520
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org
Tareq Al baghdadi
- Recruiting
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Site Public Contact, 573-334-2230, sfmc@sfmc.net
Bryan A. Faller
- Recruiting
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Mercy Hospital
Cedar Rapids, Iowa, 52403
Site Public Contact, 319-365-4673
Deborah W. Wilbur
- Recruiting
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Site Public Contact, 319-363-2690
Deborah W. Wilbur
- Recruiting
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org
Tareq Al baghdadi
- Recruiting
Baptist Memorial Hospital and Cancer Center-Collierville
Collierville, Tennessee, 38017
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Xinyu von Buttlar
- Recruiting
Baptist Memorial Hospital and Cancer Center-Golden Triangle
Columbus, Mississippi, 39705
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Xinyu von Buttlar
- Recruiting
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
Decatur Memorial Hospital
Decatur, Illinois, 62526
Site Public Contact, 217-876-4762, morganthaler.jodi@mhsil.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Parkland Health Center - Farmington
Farmington, Missouri, 63640
Site Public Contact, 314-996-5569
Bryan A. Faller
- Recruiting
Highlands Oncology Group - Fayetteville
Fayetteville, Arkansas, 72703
Site Public Contact, 479-872-8100, research@hogonc.com
Joseph T. Beck
- Recruiting
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Baptist Cancer Center-Grenada
Grenada, Mississippi, 38901
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Xinyu von Buttlar
- Recruiting
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, 72401
Site Public Contact, 870-936-7066, Emily.Carvell@bmhcc.org
Xinyu von Buttlar
- Recruiting
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org
Tareq Al baghdadi
- Recruiting
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, 38120
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Xinyu von Buttlar
- Recruiting
Baptist Memorial Hospital and Cancer Center-Union County
New Albany, Mississippi, 38652
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Xinyu von Buttlar
- Recruiting
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Baptist Memorial Hospital and Cancer Center-Oxford
Oxford, Mississippi, 38655
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Xinyu von Buttlar
- Recruiting
Lahey Medical Center-Peabody
Peabody, Massachusetts, 01960
Site Public Contact, 781-744-3421, lhmc-cancer-clinical-trials@lahey.org
Brendan Connell
- Recruiting
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Peru
Peru, Illinois, 61354
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Highlands Oncology Group - Rogers
Rogers, Arkansas, 72758
Site Public Contact, 479-872-8130, research@hogonc.com
Joseph T. Beck
- Recruiting
Sainte Genevieve County Memorial Hospital
Sainte Genevieve, Missouri, 63670
Site Public Contact, 314-996-5569
Bryan A. Faller
- Recruiting
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi, 38671
Site Public Contact, 901-226-1366, BCCclintrials@bmhcc.org
Xinyu von Buttlar
- Recruiting
Highlands Oncology Group
Springdale, Arkansas, 72762
Site Public Contact, 479-872-8130, research@hogonc.com
Joseph T. Beck
- Recruiting
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Site Public Contact, 217-545-7929
Bryan A. Faller
- Recruiting
Missouri Baptist Medical Center
St Louis, Missouri, 63131
Site Public Contact, 314-996-5569
Bryan A. Faller
- Recruiting
Missouri Baptist Sullivan Hospital
Sullivan, Missouri, 63080
Site Public Contact, 314-996-5569
Bryan A. Faller
- Recruiting
Illinois CancerCare - Washington
Washington, Illinois, 61571
Site Public Contact, 309-243-3605, andersonj@illinoiscancercare.com
Bryan A. Faller
- Recruiting
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
Site Public Contact, 734-712-7251, MCRCwebsitecontactform@stjoeshealth.org
Tareq Al baghdadi
About this study
Official title: Phase III Double Blinded Trial of Immune-Based Therapy With a Live Biotherapeutic MO-03 or Placebo for Frontline Therapy of Advanced Clear Cell Renal Cell Carcinoma [BioFront Trial]
This phase III trial compares the effect of adding live biotherapy, MO-03, to standard of care (SOC) immunotherapy, including ipilimumab, nivolumab, axitinib, pembrolizumab, cabozantinib, and lenvatinib, to SOC immunotherapy alone in treating patients with clear cell renal cell cancer that may have spread from where it first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started to other places in the body (metastatic). Studies have shown that gut health (the gut microbiome) may impact the effectiveness of immunotherapy. The microbiome includes all of the bacteria and organisms naturally found in the digestive tract. MO-03, a type of biotherapy, contains material from living organisms that may help keep the digestive tract healthy and may help to increase the effect of immunotherapy. Immunotherapy with monoclonal antibodies, such as ipilimumab, nivolumab, pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are a type of angiogenesis inhibitor and tyrosine kinase inhibitor (TKI) that block certain proteins which may help keep tumor cells from growing and may also help prevent the growth of new blood vessels that tumors need to grow. Adding MO-03 to SOC immunotherapy may be more effective than SOC immunotherapy alone in treating patients with advanced or metastatic clear cell renal cell cancer.
Read the detailed description
PRIMARY OBJECTIVE:
- To compare investigator assessed progression-free survival of participants with advanced clear cell renal cell carcinoma (ccRCC) randomized to standard of care immunotherapy (IO)-based combination regimen plus placebo versus IO-based combination regimen plus clostridium butyricum CBM 588 probiotic strain (MO-03) in an intent-to-treat analysis.
SECONDARY OBJECTIVES:
- For the safety run-in: To assess the safety of MO-03 when added to each of the following standard frontline treatment regimens for advanced renal cell carcinoma: cabozantinib/nivolumab, axitinib/pembrolizumab (MK-3475) and lenvatinib/pembrolizumab (MK-3475) in the first 50 randomized patients after receiving at least two cycles of treatment.
II. To compare investigator assessed Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 response (confirmed and unconfirmed complete response and partial response) between the study arms.
III. To compare overall survival (OS) between the study arms. IV. To compare investigator assessed progression free survival (PFS) rates between the study arms at 12 months and at 24 months.
- To evaluate the qualitative and quantitative toxicities between the study arms.
ADDITIONAL OBJECTIVES:
- To compare time to subsequent systemic therapy between the study arms. II. To evaluate the potential impact of concomitant medications, specifically antibiotics, proton pump inhibitors (PPI) and steroids, on the activity of MO-03 in combination with standard immune checkpoint inhibitors (ICI) based regimen.
TRANSLATIONAL MEDICINE BANKING OBJECTIVE:
- To bank archival tissue, blood and stool samples for future contemporary translational studies.
OUTLINE: Patients are randomized to 1 of 2 arms and are assigned to 1 of 4 regimens based on risk status.
ARM 1: Patients receive MO-03 orally (PO) twice daily (BID) on days 1-42 of each cycle. Cycles repeat every 42 days for up to 3 years in the absence of disease progression or unacceptable toxicity. In addition, intermediate or poor-risk patients also receive SOC immunotherapy regimens 1, 2, 3, or 4 and favorable risk patients receive SOC immunotherapy regimens 2, 3, or 4.
ARM 2: Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 42 days for up to 3 years in the absence of disease progression or unacceptable toxicity. In addition, intermediate or poor-risk patients also receive SOC immunotherapy regimens 1, 2, 3, or 4 and favorable risk patients receive SOC immunotherapy regimens 2, 3, or 4.
REGIMEN 1: Patients receive SOC ipilimumab intravenously (IV) over 30-90 minutes and nivolumab IV or nivolumab and recombinant human hyaluronidase subcutaneously (SC) every 21 days for up to 4 infusions in the absence of disease progression or unacceptable toxicity. After completing 4 infusions, patients continue to receive nivolumab IV or nivolumab and recombinant human hyaluronidase SC every 14 or 28 days in the absence of disease progression or unacceptable toxicity.
REGIMEN 2: Patients receive SOC axitinib PO BID for up to 3 years in the absence of disease progression or unacceptable toxicity. Patients also receive SOC pembrolizumab IV every 21 or 42 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
REGIMEN 3: Patients receive SOC cabozantinib PO once daily (QD) for up to 3 years in the absence of disease progression or unacceptable toxicity. Patients also receive SOC nivolumab IV or nivolumab and recombinant human hyaluronidase SC every 14 or 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
REGIMEN 4: Patients receive SOC lenvatinib PO QD for up to 3 years in the absence of disease progression or unacceptable toxicity. Patients also receive SOC pembrolizumab IV every 21 or 42 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
All patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection throughout the study. Additionally, patients with suspected bone metastasis may undergo bone scan throughout the study and patients with suspected brain metastasis may undergo brain MRI throughout the study
After completion of study treatment, patients are followed every 6 months for the first 2 years then once a year for years 3-5.
- Conditions
- Advanced Clear Cell Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8
- Being tested
- Axitinib, Biospecimen Collection, Bone Scan, Cabozantinib, Clostridium butyricum CBM 588 Probiotic Strain
- Medical subject headings
- Clear-cell metastatic renal cell carcinoma, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AxitinibDrug
Also called AG 013736, AG-013736, AG013736, Inlyta
Given PO
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Bone ScanProcedure or surgery
Also called Bone Scintigraphy
Undergo bone scan
CabozantinibDrug
Given PO
Clostridium butyricum CBM 588 Probiotic StrainDrug
Also called C. butyricum CBM 588 Probiotic Strain, C. butyricum MIYAIRI Strain, C. butyricum Strain MIYAIRI 588, CBM 588
Given PO
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
IpilimumabBiological
Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016
Given IV
LenvatinibDrug
Also called E 7080, E-7080, E7080, ER-203492-00
Given PO
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
NivolumabBiological
Also called ABP 206, BCD-263, BMS 936558, BMS-936558
Given IV
Nivolumab and Recombinant Human HyaluronidaseDrug
Also called Hyaluronidase-nvhy and Nivolumab, Hyaluronidase/Nivolumab, Nivolumab and Hyaluronidase-nvhy, Nivolumab and rHuPH20
Given SC
PembrolizumabBiological
Also called BCD-201, GME 751, GME751, Keytruda
Given IV
Placebo AdministrationDrug
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (MO-03, SOC immunotherapy) | Experimental | See Detailed Description Receives: Drug: Axitinib; Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Cabozantinib; Drug: Clostridium butyricum CBM 588 Probiotic Strain; Procedure: Computed Tomography; Biological: Ipilimumab; Drug: Lenvatinib; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Drug: Nivolumab and Recombinant Human Hyaluronidase; Biological: Pembrolizumab |
| Arm 2 (placebo, SOC immunotherapy) | Placebo comparator | See Detailed Description Receives: Drug: Axitinib; Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Cabozantinib; Procedure: Computed Tomography; Biological: Ipilimumab; Drug: Lenvatinib; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Drug: Nivolumab and Recombinant Human Hyaluronidase; Biological: Pembrolizumab; Drug: Placebo Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
A Cox model will be used to test the treatment hazard ratio with stratification factors in the model as covariates for the futility and efficacy interim analyses and the final analysis.
Measured: From date of randomization to date of first documentation of progression, or death due to any cause, assessed up to 5 years
Secondary outcomes (4)
Incidence of adverse events (AEs) (Safety run-in)
Will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The rate and severity of toxicities on the active arm will be compared to the placebo arm to provide context for the background rate of toxicities attributable to the standard of care regimens.
Measured: During the first 12 weeks (2 cycles [cycle length =42 days])
Overall survival
Will report the hazard ratio and 95% confidence interval for blinded study agent with respect to overall survival with stratification in the Cox model for the stratification factors.
Measured: From date of randomization to date of death due to any cause, assessed up to 5 years
PFS rates between the study arms
Estimates of treatment effect and the corresponding 95% confidence interval will be provided for the PFS endpoint for sex, race, and ethnicity.
Measured: At 12 and 24 months
Incidence of AEs between study arms
Will be assessed according to the NCI CTCAE v 5.0. The rate and severity of toxicities on the active arm will be compared to the placebo arm to provide context for the background rate of toxicities attributable to the standard of care regimens.
Measured: Up to 90 days after last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2026
- Study start5 Jun 2026
- Primary completion31 Jan 2033 (estimated)
- Study completion31 Jan 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by SWOG Cancer Research NetworkThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 718 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SWOG Cancer Research Network
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Pedro Barata, Principal investigator, SWOG Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07383441
- Sponsor's protocol ID
- S2419
- Other IDs
- NCI-2026-00080, S2419, S2419, U10CA180888
- Status last verified
- Jun 2026
- First submitted
- 26 Jan 2026
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Double Blinded Trial of Immune-Based Therapy With a Live Biotherapeutic MO-03 or Placebo for Frontline Therapy of Advanced Clear Cell Renal Cell Carcinoma [BioFront Trial]
- ClinicalTrials.gov ID
- NCT07383441
- Acronym / sponsor ID
- S2419
- Conditions
- Advanced Clear Cell Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 718 participants (estimated)
- Lead sponsor
- SWOG Cancer Research NetworkResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 5 Jun 2026 (actual)
- Primary completion
- 31 Jan 2033 (estimated)
- Study completion
- 31 Jan 2034 (estimated)
- First posted
- 3 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase III trial compares the effect of adding live biotherapy, MO-03, to standard of care (SOC) immunotherapy, including ipilimumab, nivolumab, axitinib, pembrolizumab, cabozantinib, and lenvatinib, to SOC immunotherapy alone in treating patients with clear cell renal cell cancer that may have spread from where it first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started to other places in the body (metastatic). Studies have shown that gut health (the gut microbiome) may impact the effectiveness of immunotherapy. The microbiome includes all of the bacteria and organisms naturally found in the digestive tract. MO-03, a type of biotherapy, contains material from living organisms that may help keep the digestive tract healthy and may help to increase the effect of immunotherapy. Immunotherapy with monoclonal antibodies, such as ipilimumab, nivolumab, pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are a type of angiogenesis inhibitor and tyrosine kinase inhibitor (TKI) that block certain proteins which may help keep tumor cells from growing and may also help prevent the growth of new blood vessels that tumors need to grow. Adding MO-03 to SOC immunotherapy may be more effective than SOC immunotherapy alone in treating patients with advanced or metastatic clear cell renal cell cancer.
Detailed description
PRIMARY OBJECTIVE:
- To compare investigator assessed progression-free survival of participants with advanced clear cell renal cell carcinoma (ccRCC) randomized to standard of care immunotherapy (IO)-based combination regimen plus placebo versus IO-based combination regimen plus clostridium butyricum CBM 588 probiotic strain (MO-03) in an intent-to-treat analysis.
SECONDARY OBJECTIVES:
- For the safety run-in: To assess the safety of MO-03 when added to each of the following standard frontline treatment regimens for advanced renal cell carcinoma: cabozantinib/nivolumab, axitinib/pembrolizumab (MK-3475) and lenvatinib/pembrolizumab (MK-3475) in the first 50 randomized patients after receiving at least two cycles of treatment.
II. To compare investigator assessed Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 response (confirmed and unconfirmed complete response and partial response) between the study arms.
III. To compare overall survival (OS) between the study arms. IV. To compare investigator assessed progression free survival (PFS) rates between the study arms at 12 months and at 24 months.
- To evaluate the qualitative and quantitative toxicities between the study arms.
ADDITIONAL OBJECTIVES:
- To compare time to subsequent systemic therapy between the study arms. II. To evaluate the potential impact of concomitant medications, specifically antibiotics, proton pump inhibitors (PPI) and steroids, on the activity of MO-03 in combination with standard immune checkpoint inhibitors (ICI) based regimen.
TRANSLATIONAL MEDICINE BANKING OBJECTIVE:
- To bank archival tissue, blood and stool samples for future contemporary translational studies.
OUTLINE: Patients are randomized to 1 of 2 arms and are assigned to 1 of 4 regimens based on risk status.
ARM 1: Patients receive MO-03 orally (PO) twice daily (BID) on days 1-42 of each cycle. Cycles repeat every 42 days for up to 3 years in the absence of disease progression or unacceptable toxicity. In addition, intermediate or poor-risk patients also receive SOC immunotherapy regimens 1, 2, 3, or 4 and favorable risk patients receive SOC immunotherapy regimens 2, 3, or 4.
ARM 2: Patients receive placebo PO BID on days 1-42 of each cycle. Cycles repeat every 42 days for up to 3 years in the absence of disease progression or unacceptable toxicity. In addition, intermediate or poor-risk patients also receive SOC immunotherapy regimens 1, 2, 3, or 4 and favorable risk patients receive SOC immunotherapy regimens 2, 3, or 4.
REGIMEN 1: Patients receive SOC ipilimumab intravenously (IV) over 30-90 minutes and nivolumab IV or nivolumab and recombinant human hyaluronidase subcutaneously (SC) every 21 days for up to 4 infusions in the absence of disease progression or unacceptable toxicity. After completing 4 infusions, patients continue to receive nivolumab IV or nivolumab and recombinant human hyaluronidase SC every 14 or 28 days in the absence of disease progression or unacceptable toxicity.
REGIMEN 2: Patients receive SOC axitinib PO BID for up to 3 years in the absence of disease progression or unacceptable toxicity. Patients also receive SOC pembrolizumab IV every 21 or 42 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
REGIMEN 3: Patients receive SOC cabozantinib PO once daily (QD) for up to 3 years in the absence of disease progression or unacceptable toxicity. Patients also receive SOC nivolumab IV or nivolumab and recombinant human hyaluronidase SC every 14 or 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
REGIMEN 4: Patients receive SOC lenvatinib PO QD for up to 3 years in the absence of disease progression or unacceptable toxicity. Patients also receive SOC pembrolizumab IV every 21 or 42 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
All patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection throughout the study. Additionally, patients with suspected bone metastasis may undergo bone scan throughout the study and patients with suspected brain metastasis may undergo brain MRI throughout the study
After completion of study treatment, patients are followed every 6 months for the first 2 years then once a year for years 3-5.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (MO-03, SOC immunotherapy) | Experimental | Drug: Axitinib, Procedure: Biospecimen Collection, Procedure: Bone Scan, Drug: Cabozantinib, Drug: Clostridium butyricum CBM 588 Probiotic Strain, Procedure: Computed Tomography, Biological: Ipilimumab, Drug: Lenvatinib, Procedure: Magnetic Resonance Imaging, Biological: Nivolumab, Drug: Nivolumab and Recombinant Human Hyaluronidase, Biological: PembrolizumabSee Detailed Description |
| Arm 2 (placebo, SOC immunotherapy) | Placebo comparator | Drug: Axitinib, Procedure: Biospecimen Collection, Procedure: Bone Scan, Drug: Cabozantinib, Procedure: Computed Tomography, Biological: Ipilimumab, Drug: Lenvatinib, Procedure: Magnetic Resonance Imaging, Biological: Nivolumab, Drug: Nivolumab and Recombinant Human Hyaluronidase, Biological: Pembrolizumab, Drug: Placebo AdministrationSee Detailed Description |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (38 listed)
- Participants must have histologically confirmed renal cell carcinoma (RCC) with clear cell component that is advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC at the time of registration on study
- Participants must have measurable/evaluable disease by RECIST 1.1 criteria. Participants with only bone metastases or only pleural effusions are considered evaluable disease and are eligible
- Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease must not require immediate central nervous system (CNS) specific treatment at the time of study registration or anticipated treatment during the first cycle of therapy
- Participants must not be currently enrolled or plan to participate in treatment studies while enrolled on this study
- Participants must not plan to take any over the counter probiotic supplements at time of study registration and while on protocol treatment
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AxitinibAlso: AG 013736, AG-013736, AG013736, InlytaGiven PO | Drug | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| Bone ScanAlso: Bone ScintigraphyUndergo bone scan | Procedure or surgery | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| CabozantinibGiven PO | Drug | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| Clostridium butyricum CBM 588 Probiotic StrainAlso: C. butyricum CBM 588 Probiotic Strain, C. butyricum MIYAIRI Strain, C. butyricum Strain MIYAIRI 588, CBM 588Given PO | Drug | Arm 1 (MO-03, SOC immunotherapy) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT | Procedure or surgery | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| IpilimumabAlso: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016Given IV | Biological | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| LenvatinibAlso: E 7080, E-7080, E7080, ER-203492-00Given PO | Drug | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI | Procedure or surgery | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| NivolumabAlso: ABP 206, BCD-263, BMS 936558, BMS-936558Given IV | Biological | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| Nivolumab and Recombinant Human HyaluronidaseAlso: Hyaluronidase-nvhy and Nivolumab, Hyaluronidase/Nivolumab, Nivolumab and Hyaluronidase-nvhy, Nivolumab and rHuPH20Given SC | Drug | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| PembrolizumabAlso: BCD-201, GME 751, GME751, KeytrudaGiven IV | Biological | Arm 1 (MO-03, SOC immunotherapy), Arm 2 (placebo, SOC immunotherapy) |
| Placebo AdministrationGiven PO | Drug | Arm 2 (placebo, SOC immunotherapy) |
Primary outcome
Progression-free survival (PFS)
Time frame: From date of randomization to date of first documentation of progression, or death due to any cause, assessed up to 5 years
A Cox model will be used to test the treatment hazard ratio with stratification factors in the model as covariates for the futility and efficacy interim analyses and the final analysis.
4 secondary outcomes
Incidence of adverse events (AEs) (Safety run-in)
Time frame: During the first 12 weeks (2 cycles [cycle length =42 days])
Overall survival
Time frame: From date of randomization to date of death due to any cause, assessed up to 5 years
PFS rates between the study arms
Time frame: At 12 and 24 months
Incidence of AEs between study arms
Time frame: Up to 90 days after last dose of study treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, United States
Pedro Barata principal investigator
SWOG Cancer Research Network
41 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Axitinib, Biospecimen Collection and Bone Scan in people with Advanced Clear Cell Renal Cell Carcinoma and Metastatic Clear Cell Renal Cell Carcinoma, run by SWOG Cancer Research Network at 41 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 38 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) (time frame: From date of randomization to date of first documentation of progression, or death due to any cause, assessed up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.