The goal of this clinical research study is to find the highest tolerable or recommended
dose of MGCD5 that can be given with nivolumab to patients with kidney cancer. Researchers
also want to learn if this dose can help to control the disease. The safety of this drug
combination will also be studied.
If you are found to be eligible to take part in this study, you will be assigned to 1 of 4
dose levels based on when you join this study. The dose of MGCD516 you receive will depend
on how well previously enrolled patients tolerated the study drug. All participants will
receive the same dose of nivolumab.
Study Drug Administration:
Each study cycle is 14 days (2 weeks).
You will take MGCD516 by mouth every day while you are on study. Each dose should be taken
in the morning at about the same time each day. You should take MGCD516 at least 2 hours
after and 1 hour before your next meal. For example, you can take your dose in the morning
at least 1 hour before breakfast.
You will be given a study drug diary to keep track of when you take each dose and if you
miss or vomit any doses. You should return any empty study drug bottles or leftover study
drug to the clinic at the beginning of each cycle.
You will also receive nivolumab by vein over 60 minutes on Day 1 of Cycles 2 and beyond. You
will not receive nivolumab during Cycle 1.
Length of Study:
You may continue to receive the study drugs for as long as the study doctor thinks it is in
your best interest. You will no longer be able to take the study drugs if the disease gets
worse, if intolerable side effects occur, or if you are unable to follow study directions.
Every 2 weeks:
- You will have a physical exam.
- Blood (about 1 teaspoon) will be drawn for routine tests.
At Weeks 6 and 12 and then every 12 weeks after that:
- You will have an MRI and/or CT scan. If needed, you may also have an x-ray or bone
- Blood (about 3 teaspoons) will be drawn to check the level of sugar in your blood. You
must fast for 8 hours before this test.
- If the doctor thinks it is needed, urine will be collected for routine tests.
At Week 12 and then every 6 months after that, you will have an ECHO or MUGA scan. You may
have this test more often if the doctor thinks it's needed.
About 30 days after your last dose of study drugs:
- You will have a physical exam.
- If the doctor thinks it is needed, you may have a CT or MRI scan.
You will be called by a member of the study staff every 3 months to ask how you are doing
and if you have started any new anti-cancer treatments. This information may be collected
from your medical record instead. This phone call should take about 5-10 minutes.
These calls will stop if you decide you no longer want to take part in this study.
This is an investigational study. MGCD516 is not FDA approved or commercially available. It
is currently being used for research purposes only. Nivolumab is FDA approved and
commercially available for the treatment of many types of cancer, including kidney cancer.
The study doctor can explain how the study drugs are designed to work.
Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.
1. Patients with histologically or cytologically confirmed metastatic/advanced clear
cell RCC, or RCC with a clear cell component, who have received 1 or 2 prior
anti-angiogenic therapy regimens (+/- cytokine therapy with interleukin-2 or
interferon-alfa) in the advanced or metastatic setting. Examples of anti-angiogenic
agents include, but are not limited to, sorafenib, sunitinib, pazopanib, axitinib,
2. There must be evidence of progression on or after last treatment regimen received and
within 6 months of enrollment.
3. Patients must have at least one measurable site of disease, defined as a lesion that
can be accurately measured in at least one dimension (longest diameter to be
recorded) and measures >/= 15 mm with conventional techniques or >/=10 mm with more
sensitive techniques such as MRI or spiral CT scan. If the patient has had previous
radiation to the marker lesion(s), there must be evidence of progression since the
4. Karnofsky performance status >/=70
5. Age >/=18 years
6. Patients must have adequate organ and marrow function within 14 days prior to study
entry as defined below: Hemoglobin >/= 9 g/dl (treatment allowed); absolute
neutrophil count >/= 1,500/uL; platelets >/= 100,000/uL; total bilirubin </= 1.5
mg/dl; AST(SGOT) or ALT (SGPT) </= 2.5 X institutional uln,except in known hepatic
metastasis, wherein may be < 5 x ULN; Serum Creatinine </= 1.5 x ULN (as long as
patient does not require dialysis)
7. INR and PTT </= 1.5 x ULN within 14 days prior to study entry. Therapeutic
anticoagulation with warfarin is allowed if target INR </= 3 on a stable dose of
warfarin or on a stable dose of low molecular weight (LMW) heparin for > 2 weeks (14
days) at the time of enrollment.
8. Female patients of childbearing potential (not postmenopausal for at least 12 months
and not surgically sterile) must have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days before study
entry. Pregnancy test must be repeated if performed > 14 days before starting study
9. Women must not be breastfeeding
10. Patients must give written informed consent prior to study entry, in keeping with the
policies of the institution.
11. Patients with a history of major psychiatric illness must be judged (by the treating
physician) able to fully understand the investigational nature of the study and the
risks associated with the therapy.
12. Patients with controlled brain metastases are allowed on protocol if they had
solitary brain metastases that was surgically resected or treated with radiosurgery
or Gamma knife, without recurrence or edema for 1 month (4 weeks).
1. Patients must not have any other malignancies within the past 2 years except for in
situ carcinoma of any site, or adequately treated (without recurrence post-resection
or post-radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of
2. Patients currently receiving anticancer therapies or who have received anticancer
therapies within 4 weeks (28 days) from enrollment into this study (including
chemotherapy and targeted therapy) are excluded. Also, patients who have completed
palliative radiation therapy more than 14 days prior to the first dose of MGCD516 are
3. Patients, who have had a major surgery or significant traumatic injury (injury
requiring > 4 weeks (28 days) to heal) within 4 weeks (28 days) of start of study
drug, patients who have not recovered from the side effects of any major surgery
(defined as requiring general anesthesia) or patients that are expected to require
major surgery during the course of the study.
4. Patients who have been previously treated with mTOR inhibitors such as everolimus and
temsirolimus, or with c-MET inhibitors such as cabozantinib
5. Patients who have organ allografts.
6. Known or suspected autoimmune disease. Patients with a history of inflammatory bowel
disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders
such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic
Lupus Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are
excluded from this study. Patients with a history of Hashimoto's thyroiditis only
requiring hormone replacement, Type I diabetes, or psoriasis not requiring systemic
treatment, or conditions not expected to recur in the absence of an external trigger
are allowed to participate.
7. Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).
8. Any underlying medical condition, which in the opinion of the Investigator, will make
the administration of study drug hazardous or obscure the interpretation of adverse
events, such as a condition associated with frequent diarrhea, uncontrolled nausea,
vomiting, malabsorption syndrome or small bowel resection that may significantly
alter the absorption of MGCD516.
9. Patients must not have received prior anticancer therapy with any immune checkpoint
inhibitors such as anti-CLTA-4, anti-PD1, or anti-PD-L1.
10. Patients receiving any concomitant systemic therapy for renal cell cancer are
11. Patients must not be scheduled to receive another experimental drug while on this
12. Patients who are on high dose steroid (e.g., > 10mg prednisone daily or equivalent)
or other more potent immune suppression medications (e.g., infliximab). Topical,
inhaled, intra-articular, ocular, or intranasal corticosteroids (with minimal
systemic absorption) are allowed. A brief course (</=48 hours) of systemic
corticosteroids for prophylaxis (eg, from contrast dye allergy) is permitted.
13. Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation in the study such as: Symptomatic
congestive heart failure of New York heart Association Class III or IV; unstable
angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6
months of start of study drug, serious uncontrolled cardiac arrhythmia or any other
clinically significant cardiac disease; severely impaired lung function as defined as
02 saturation that is 88% or less at rest on room air; uncontrolled diabetes as
defined by fasting serum glucose >1.5 x ULN; Systemic fungal, bacterial, viral, or
other infection that is not controlled (defined as exhibiting ongoing signs/symptoms
related to the infection and without improvement) despite appropriate antibiotics or
14. Exclusion #13 continued: Liver disease such as cirrhosis or chronic active hepatitis;
Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or
positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV
antibody test indicating acute or chronic infection.
15. Patients must not have history of other diseases, metabolic dysfunction, physical
examination finding, or clinical laboratory finding giving reasonable suspicion of a
disease or condition that contraindicates the use of MGCD516 or nivolumab or that
might affect the interpretation of the results of the study or render the subject at
high risk from treatment complications.
16. Patients should not receive immunization with attenuated live vaccines within one
week (7 days) of study entry or during study period.
17. Uncontrolled brain or leptomeningeal metastases, including patients who continue to
require glucocorticoids for brain or leptomeningeal metastases.
18. Female patients who are pregnant or breast feeding, or adults of reproductive
potential who are not using effective birth control methods. If barrier
contraceptives are being used, these must be continued throughout the trial by both
sexes. Hormonal contraceptives are not acceptable as a sole method of contraception.
(Women of childbearing potential must have a negative urine or serum pregnancy test
within 14 days prior to study entry. Pregnancy test must be repeated if performed >
14 days before administration of MGCD516)
19. Any patients who cannot be compliant with the appointments required in this protocol
must not be enrolled in this study.
20. Patients with LVEF <40%