MGCD516 Combined With Nivolumab in Renal Cell Cancer (RCC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03015740
Recruitment Status : Recruiting
First Posted : January 10, 2017
Last Update Posted : July 31, 2018
Mirati Therapeutics Inc.
Gateway for Cancer Research
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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.

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.

Condition or disease Intervention/treatment Phase
Malignant Neoplasms of Urinary Tract Other Disorders of Kidney and Ureter Renal Cell Carcinoma Drug: MGCD516 Drug: Nivolumab Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of MGCD516 Combined With Nivolumab in Patients With Advanced Clear Cell Renal Cell Cancer That Progressed on Prior VEGF-Targeted Therapy
Actual Study Start Date : April 23, 2017
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023

Arm Intervention/treatment
Experimental: MGCD516 + Nivolumab

Participants treated with a pre-specified daily oral dose of MGCD516 determined by the Lo-EffTox method on Day 1 of the study.

Following 2 weeks of MGCD516 monotherapy, Nivolumab additionally initiated on Day 1 of Cycles 2 and beyond.

Participants continue to receive combination therapy of MGCD516 plus Nivolumab until disease progression or unacceptable treatment-related toxicity.

Drug: MGCD516

First cohort treated at prespecified dose of 80 mg of MGCD516 by mouth every day.

All successive doses chosen by the Lo- EffTox method, and no untried dose level skipped when escalating.

Drug: Nivolumab
240 mg/kg by vein every 2 weeks on Day 1 of Cycles 2 and beyond.
Other Names:
  • BMS-936558
  • Opdivo

Primary Outcome Measures :
  1. Optimal Dose of MGCD516 Combined with Nivolumab in Participants with Advanced Clear Cell Renal Cell Cancer That Progressed on Prior VEGF-Targeted Therapy [ Time Frame: 12 weeks from the start of therapy ]

    Optimum dosage determined by occurrence of toxicities within 12 weeks from the start of therapy.

    Dose-limiting toxicity (DLT) judged by the Investigator to be clinically relevant and related (possibly or probably) to administration of either or both study drug(s).

  2. Efficacy of MGCD516 Combined with Nivolumab in Participants with Advanced Clear Cell Renal Cell Cancer That Progressed on Prior VEGF-Targeted Therapy [ Time Frame: 6 weeks ]
    Efficacy defined as achieving complete response (CR), partial response (PR), or stable disease within 6 weeks.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  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, and bevacizumab.
  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 radiation.
  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) a) May receive transfusion b) If creatinine is not <1.5×ULN, then calculate by Cockcroft-Gault methods or local institutional standard and CrC1 must be >/=40 mL/kg/1.73 m^2
  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 drug.
  9. Women must not be breastfeeding
  10. 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.
  11. 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).

Exclusion Criteria:

  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 the skin or active non-threatening second malignancy that would not, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial. Examples include but not limited to: urothelial cancer grade Ta or T1, adenocarcinoma of the prostate treated by active surveillance.
  2. Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks (14 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 eligible.
  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 excluded.
  11. Patients must not be scheduled to receive another experimental drug while on this study.
  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 blood glucose >200 mg/dl (11.1 mmol/l); 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 other treatment;
  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. Concurrent therapy with medications known to significantly prolong the QT interval and/or associated with increased risk for Torsade de Pointes arrhythmia. The Principal Investigator (PI) is the final arbiter in questions related to eligibility.
  21. Patients with LVEF <40%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03015740

Contact: Nizar M. Tannir, MD 713-792-2830

United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Mirati Therapeutics Inc.
Gateway for Cancer Research
Principal Investigator: Nizar M. Tannir, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT03015740     History of Changes
Other Study ID Numbers: 2016-0332
NCI-2017-00324 ( Registry Identifier: NCI CTRP )
G-17-600 ( Other Grant/Funding Number: GATEWAY for Cancer Research )
First Posted: January 10, 2017    Key Record Dates
Last Update Posted: July 31, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Malignant neoplasms of urinary tract
Other disorders of kidney and ureter
Renal cell carcinoma

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Urologic Neoplasms
Kidney Diseases
Ureteral Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urologic Diseases
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs