Clear Cell Renal Cell Carcinoma
Conditions
Brief summary
The goal of our study is to explore how treatments affect the bone immune microenvironment and determine the best treatment options for patients with metastatic kidney cancer to the bone. This could prevent skeletal complications and improve patient outcomes.
Detailed description
Primary Objectives: 1. To assess safety of obtaining biopsy within close time frame of cabozantinib treatment. 2. To evaluate the success rate of obtaining serial biopsies of bone metastases. Success is defined as viable single cell sequencing of bone biopsy samples at baseline and after 8 weeks of treatment. 3. To quantify the fold change in M1:M2 macrophage population in serial biopsies from renal cell carcinoma bone metastases. Secondary Objectives: 1. To compare the M1:M2 macrophage population at baseline and on therapy in paired bone versus non-bone metastatic sites. 2. To compare CD8+, Granzyme+ cells on multiplex immunofluorescence at baseline and on therapy in paired bone versus non-bone metastatic sites. 3. To describe serum marker changes over time while on therapy for bone metastasis including bone alkaline phosphatase, osteopontin, procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (â-CTX) and association with response and progression. 4. To describe overall response rate (proportion of participants who achieve a best response of complete response or partial response using RECIST 1.1 criteria), time until progression (time from initiation of systemic treatment to the date of documented disease progression), and progression-free survival (time between the first date of systemic treatment to first date of documented progression or death due to any cause). 5. To describe incidence of skeletal related events defined as a composite of pathologic fracture, spinal cord compression, radiation or surgery to bone, and hypercalcemia of malignancy. 2.3 Exploratory Objective: 1\. OPTIONAL: To describe findings in Extreme CT scan at baseline and/or at 6 months and association with skeletal related events.
Interventions
DRUGCabozantinib
Given by IV
DRUGNivolumab
Given by IV
Sponsors
M.D. Anderson Cancer Center
Exelixis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible for the study, the subject must meet all of the inclusion and none of the
Exclusion criteria
. 1. Signed Written Informed Consent 2. Ability to understand and the willingness to sign a written informed consent document. 3. Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care. 4. Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and serial biopsy schedule. 5. Participants must be willing to consent to PA-17-0577, a protocol led by Dr. Jianjun Gao, that allows for tissue sample collection and analysis 6. Type of Participant and Target Disease Characteristics 7. Histological confirmation of RCC with a clear-cell component, including participants who may also have sarcomatoid or rhabdoid features 8. Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC 9. No prior systemic therapy with nivolumab or cabozantinib or previous systemic treatment for metastatic disease. ECOG performance status ≤2 (Karnofsky ≥60%) (See Tables 1 and 2 in section 14 for reference) 10. Presence of both a bone metastasis and visceral or soft tissue metastatic lesion amenable to biopsies 11. Patients must have adequate organ and marrow function as defined below: * absolute neutrophil count ≥1,000/mcL * platelets ≥100,000/mcL * total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (Except participants with Gilbert Syndrome who must have a total bilirubin \< 3.0 x ULN) * AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN * GFR ≥30 mL/min (using the Cockcroft-Gault formula) 12. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. 13. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. 14. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Treated CNS metastases are defined as having no ongoing requirement for corticosteroids for at least 2 weeks prior to enrollment and no evidence of progression or hemorrhage after treatment completed at least 4 weeks prior to enrollment clinical examination and brain imaging (MRI or CT). 15. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. 16. Patients are eligible to receive standard of care nivolumab and cabozantinib treatment and must be prescribed this regimen at treating physician's determination. 17. Age and Reproductive Status 18. Males and females aged 18 years or greater. Because there is inadequate dosing or adverse event data in patients \<18 years of age, children are excluded from this study. 19. The effects of cabozantinib and nivolumab on the developing human fetus are unknown. For this reason and because tyrosine kinase inhibitors and immune checkpoint inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation (refer to MDA Policy CLN 1114) and for 4 months after the last dose of cabozantinib and 4 months after the last dose of nivolumab. This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: Postmenopausal (no menses in greater than or equal to 12 consecutive months). * History of hysterectomy or bilateral salpingo-oophorectomy * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). * History of bilateral tubal ligation or another surgical sterilization procedure. * In addition, females \< 55 years-of-age must have a serum follicle stimulating (FSH) level \> 40 mIU/mL to confirm menopause). 20. Approved methods of birth control are as follows: Hormonal contraception (i.e., birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. 21. Males who are sexually active with women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of study treatment and 7 months after the last dose of study treatment (ie, 90 days \[duration of sperm turnover\] plus the time required for the investigational drug to undergo approximately five half-lives). 22. Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section. Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception which have a failure rate of \< 1% when used consistently and correctly.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Adverse Events (AEs) | Through study completion; an average of 1 year | Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 |
Countries
United States
Contacts
CONTACTMatthew Campbell, MD
PRINCIPAL_INVESTIGATORMatthew Campbell, MD
M.D. Anderson Cancer Center
Outcome results
None listed