The purpose of this study is to determine if the use of immunotherapy nivolumab and the targeted therapy cabozantinib prior to removal of the kidney, will increase the number subjects who are without any visible kidney cancer in their body at some point during the course of treatment.
Recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Cabozantinib | XL184 | Treatment with cabozantinib and nivolumab with nephrectomy |
| Nivolumab | BMS-936558 | Treatment with cabozantinib and nivolumab with nephrectomy |
People with metastatic kidney cancer are usually treated with medications to slow the growth
of the cancer. In addition, people who still have the kidney where the cancer started may
have the kidney removed during the course of treatment in order to decrease the amount of
tumor in the body. This surgery is referred to as a cytoreductive nephrectomy. In the current
study, nivolumab is being administered in combination with cabozantinib. Both of these drugs
are FDA approved medications for the treatment of metastatic kidney cancer. Previous studies
have demonstrated that these two medications can be combined together without significantly
increasing the side effects beyond what is expected from each medicine individually. The
combination of nivolumab and cabozantinib for the treatment of metastatic kidney cancer is an
investigational regimen and not FDA approved for the treatment of kidney cancer.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Treatment with cabozantinib and nivolumab with nephrectomy | Experimental | All study participants will receive the same study medications, cabozantinib and nivolumab. The study drug, nivolumab, will be administered through an IV infusion every 4 weeks and cabozantinib will be administered orally daily. Initially participants will receive study treatment for 12 weeks. The cabozantinib will then be stopped prior to the nephrectomy. The first three to six subjects (group 1) will have the cabozantinib held for three weeks prior to removal of the kidney. If there are no unexpected side effects from the surgery, then future subjects (group 2) will have the cabozantinib stopped for two weeks prior to the nephrectomy. |
|
Inclusion Criteria:
- Written informed consent and HIPAA authorization for release of personal health
information.
- Age ≥ 18years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 28 days
prior to registration.
- Histological or 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:
- White blood cell (WBC) ≥ 3,000/mm3
- Absolute Neutrophil Count (ANC) ≥ 1,200/mm3
- Hemoglobin (Hgb) ≥ 9 g/dL
- Platelet ≥ 100,000
- Calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault formula
- Bilirubin ≤ 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 3 × ULN
- Alanine aminotransferase (ALT) ≤ 3 × ULN
- Albumin ≥ 2.8 g/dL
- International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated
Partial Thromboplastin Time (aPTT) within normal limits. Patients using low
molecular weight heparin are allowed on study
- 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 ≥1.3x 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.
Other exclusion criteria as specified by drug manufacturer for specific investigational
drug(s), e.g., cardiac disease, pulmonary disease.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Percentage of Participants with a Complete Response |
| Time Frame: | Up to 5 years after completion of treatment |
| Safety Issue: | |
| Description: | The percentage of participants with a complete response following treatment. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Mark Stein |
March 26, 2020
