Clinical Trials /

Sitravatinib and Nivolumab in Treating Patients With Advanced or Metastatic Kidney Cancer

NCT03015740

Description:

This phase I/II trial studies the side effects of sitravatinib and how well it works with nivolumab in treating patients with kidney cancer that has spread to other places in the body. Sitravatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sitravatinib and nivolumab may work better in treating patients with kidney cancer.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MGCD516 Combined With Nivolumab in Renal Cell Cancer (RCC)
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2016-0332
  • SECONDARY ID: NCI-2017-00324
  • NCT ID: NCT03015740

Conditions

  • Malignant Neoplasms of Urinary Tract
  • Other Disorders of Kidney and Ureter
  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
MGCD516MGCD516 + Nivolumab
NivolumabBMS-936558, OpdivoMGCD516 + Nivolumab

Purpose

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.

Detailed Description

      Study Groups:

      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.

      Study Visits:

      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
           scan.

        -  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.

      End-of-Treatment Visit:

      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.

      Long-Term Follow-Up:

      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.
    

Trial Arms

NameTypeDescriptionInterventions
MGCD516 + NivolumabExperimentalParticipants 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.
  • MGCD516
  • Nivolumab

Eligibility Criteria

        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)

          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 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).

        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.

          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
             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 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
             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. Patients with LVEF <40%
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Malignant neoplasms of urinary tract
  • Other disorders of kidney and ureter
  • Renal cell carcinoma
  • RCC
  • Metastatic
  • MGCD516
  • Nivolumab
  • BMS-936558
  • Opdivo

Last Updated

April 18, 2017