IRB Study Number 20-983
Status Recruiting
Phase Phase 2
Institute Taussig Cancer Institute
Description
Primary Objectives
• To determine biomarkers of response to nivolumab and cabozantinib through analysis of RNA-seq data obtained from pre-treatment RCC samples. Biomarkers will be ascertained through analysis of the pre-treatment TME using next-gen Cibersort and Master Regulator analysis.
• To determine the mechanism of action in responding patients and mechanism of resistance in non-responders through comparison of pre-treatment biopsies and post-treatment nephrectomy specimens thought RNA-seq based analysis of the TME using next-gen CiberSort and VIPER
Secondary Objectives
• To measure median size reduction of the primary tumor
• To measure progression free survival
• To measure response rate, one-year survival and overall survival probabilities
• To assess toxicity of this regimen
• To evaluate surgical complications using the Clavien-Dindo classification system
Inclusion Criteria
Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Age ≥ 18years at the time of consent.
ECOG Performance Status of 0-1 within 28 days prior to registration.
Radiographically consistent with metastatic renal cell carcinoma OR histological/ cytological evidence of metastatic renal cell carcinoma with a clear cell component
Measurable tumor in the kidney according to RECIST 1.1
No prior therapy for metastatic renal cell carcinoma
Demonstrate adequate organ function as defined in Table 2-1 below; all screening labs to be obtained within 14 days prior to registration. (See protocol)
Females of childbearing potential must have a negative serum pregnancy test during screening and within 24 hours of start of study drugs. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
Exclusion Criteria
Patients who had previously undergone nephrectomy for renal cancer are excluded
Uncontrolled bleeding, hypertension, or cardiovascular disease.
Prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4 inhibitors
The subject has active brain metastases or epidural disease
Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment.
The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test ≥1.3 x the laboratory ULN within 7 days before the first dose of study treatment
The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, thrombin or Factor Xa inhibitors. Aspirin (up to 325 mg/day), low-dose warfarin (≤1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
Hemoptysis of ≥0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment
Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment
Patients are excluded if they have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study start
Cardiovascular disorders including:
• Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening
• Concurrent uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
• The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) >500 ms within 28 days before randomization.
Severe active infection requiring systemic treatment within 28 days before the first dose of study treatment
Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (e.g., simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
History of organ transplant
Concurrent uncompensated hypothyroidism
Unable to swallow tablets
Active infection requiring systemic therapy
Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least 2 years.
Active central nervous system (CNS) metastases
Treatment with any investigational drug within 28 days prior to registration.
