Adding Biotherapy or Placebo to Standard Treatment for Advanced Kidney Cancer
Purpose
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.
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
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- 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
- 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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Care Provider)
- Masking Description
- Double blinded trial
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm 1 (MO-03, SOC immunotherapy) |
See Detailed Description |
|
|
Placebo Comparator Arm 2 (placebo, SOC immunotherapy) |
See Detailed Description |
|
Recruiting Locations
Fayetteville, Arkansas 72703
Jonesboro, Arkansas 72401
Rogers, Arkansas 72758
Springdale, Arkansas 72762
Bloomington, Illinois 61704
Canton, Illinois 61520
Carthage, Illinois 62321
Decatur, Illinois 62526
Decatur, Illinois 62526
Eureka, Illinois 61530
Galesburg, Illinois 61401
Kewanee, Illinois 61443
Macomb, Illinois 61455
Ottawa, Illinois 61350
Pekin, Illinois 61554
Peoria, Illinois 61615
Peru, Illinois 61354
Princeton, Illinois 61356
Springfield, Illinois 62702
Site Public Contact
217-545-7929
Washington, Illinois 61571
Cedar Rapids, Iowa 52403
Site Public Contact
319-365-4673
Cedar Rapids, Iowa 52403
Site Public Contact
319-363-2690
Burlington, Massachusetts 01805
Peabody, Massachusetts 01960
Brighton, Michigan 48114
Canton, Michigan 48188
Chelsea, Michigan 48118
Livonia, Michigan 48154
Ypsilanti, Michigan 48197
Columbus, Mississippi 39705
Grenada, Mississippi 38901
New Albany, Mississippi 38652
Oxford, Mississippi 38655
Southhaven, Mississippi 38671
Cape Girardeau, Missouri 63703
Farmington, Missouri 63640
Site Public Contact
314-996-5569
Sainte Genevieve, Missouri 63670
Site Public Contact
314-996-5569
St Louis, Missouri 63131
Site Public Contact
314-996-5569
Sullivan, Missouri 63080
Site Public Contact
314-996-5569
Collierville, Tennessee 38017
Memphis, Tennessee 38120
More Details
- Status
- Recruiting
- Sponsor
- SWOG Cancer Research Network
Study Contact
Detailed Description
PRIMARY OBJECTIVE: I. 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: I. 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. V. To evaluate the qualitative and quantitative toxicities between the study arms. ADDITIONAL OBJECTIVES: I. 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: I. 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.