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Clear Cell Renal Cell CarcinomaPhase 1/2NCT03015740

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

A Phase 1/2 study testing Laboratory Biomarker Analysis, Nivolumab and Quality-of-Life Assessment in people with Clear Cell Renal Cell Carcinoma and Metastatic Kidney Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Nivolumab and Quality-of-Life Assessment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
23 Apr 2017to 6 Sep 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • There must be evidence of progression on or after last treatment regimen received and within 6 months of enrollment
  • 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 magnetic resonance imaging (MRI) or spiral computed tomography (CT) scan; if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
  • Karnofsky performance status >= 70
  • Hemoglobin >= 9 g/dl (treatment allowed) (within 14 days prior to study entry)
  • Absolute neutrophil count >= 1,500/uL (within 14 days prior to study entry)
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  • Platelets >= 100,000/uL (within 14 days prior to study entry)
  • Total bilirubin =< 1.5 mg/dl (within 14 days prior to study entry)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN), except in known hepatic metastasis, wherein may be < 5 x ULN (within 14 days prior to study entry)
  • 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 x ULN, then calculate by Cockcroft-Gault methods or local institutional standard and creatinine clearance (CrCl) must be >= 40 mL/kg/1.73 m^2 (within 14 days prior to study entry)
  • International normalized ratio (INR) and partial thromboplastin time (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
  • 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 human chorionic gonadotropin [HCG]) within 14 days before study entry; pregnancy test must be repeated if performed > 14 days before starting study drug
  • Women must not be breastfeeding
  • 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
  • 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)

Who cannot join

  • 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
  • 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
  • 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
  • Patients who have been previously treated with mTOR inhibitors such as everolimus and temsirolimus, or with c-MET inhibitors such as cabozantinib
  • Patients who have organ allografts
  • 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
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  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • 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
  • Patients must not have received prior anticancer therapy with any immune checkpoint inhibitors such as anti-CLTA-4, anti-PD1, or anti-PD-L1
  • Patients receiving any concomitant systemic therapy for renal cell cancer are excluded
  • Patients must not be scheduled to receive another experimental drug while on this study
  • Patients who are on high dose steroid (e.g., > 10 mg 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 (e.g., from contrast dye allergy) is permitted
  • 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 oxygen (O2) 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; 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
  • 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
  • Patients should not receive immunization with attenuated live vaccines within one week (7 days) of study entry or during study period
  • Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
  • 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)
  • Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study
  • 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
  • Patients with left ventricular ejection fraction (LVEF) < 40%

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the toxicities (defined as a grade 3 or 4 National Cancer Institute [NCI] non-hematologic or hematologic adverse event, within 12 weeks from treatment initiation), and efficacy (defined as achieving complete remission, partial remission, or stable disease within 6 weeks) of sitravatinib (MGCD516) when administered orally (PO) daily in combination with standard dose nivolumab 240 mg/kg every 2 weeks.

SECONDARY OBJECTIVES:

  1. To estimate the overall survival (OS), progression-free survival (PFS) times, objective response rates (ORR), and quality of life (QOL) of patients with advanced clear cell renal cell cancer (RCC) treated with the combination of MGCD516 and nivolumab.

II. Evaluate potential biomarkers for patient stratification and treatment response, including genetic analysis, serum cytokines and chemokines, as well as tumor antigen-specific immune responses, such as antibody and T cell responses, as surrogates for anti-tumor activity.

OUTLINE:

Patients receive sitravatinib PO once daily (QD) on days 1-14 and receive nivolumab intravenously (IV) over 60 minutes on day 1 starting cycle 2. Cycles repeat every 14 days for cycles 1-6 and then every 28 days for subsequent cycles in the absence of disease progression or unacceptable toxicity. Patients who receive at least 6 infusions of nivolumab with no dose limiting toxicities (DLTs) related to nivolumab, may then receive nivolumab every 4 weeks.

After completion of study treatment, patients are followed up at 30 days and then every 3 months.

Being tested
Laboratory Biomarker Analysis, Nivolumab, Quality-of-Life Assessment, Questionnaire Administration, Sitravatinib
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • SitravatinibDrug

    Also called MGCD516

    Given PO

Study groups in NCT03015740
Study groupRoleWhat they receive
Treatment (sitravatinib, nivolumab)ExperimentalPatients receive sitravatinib PO QD on days 1-14 and receive nivolumab IV over 60 minutes on day 1 starting cycle 2. Cycles repeat every 14 days for cycles 1-6 and then every 28 days for subsequent cycles in the absence of disease progression or unacceptable toxicity. Patients who receive at least 6 infusions of nivolumab with no DLTs related to nivolumab, may then receive nivolumab every 4 weeks.
Receives: Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Sitravatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

    To determine the toxicities (defined as a grade 3 or 4 National Cancer Institute [NCI] non-hematologic or hematologic adverse event, within 12 weeks from treatment initiation),and efficacy (defined as achieving complete remission, partial remission, or stable disease within 6 weeks) of dosing.

    Measured: from enrollment up to 12 weeks for each dosing group

Secondary outcomes (3)

  1. Overall Survival (OS)

    To estimate the overall survival (OS) of patients with advanced clear cell renal cell cancer (RCC) treated with the combination of MGCD516 and nivolumab. The Secondary objective of the protocol is to capture combined results from all subjects who received treatment of the combination therapy. The intent was not to report results for each arm/group.

    Measured: From enrollment to study completion, up to 5 years 4 months

  2. Progression-free Survival (PFS) Times

    To estimate the progression-free survival (PFS) times of patients with advanced clear cell renal cell cancer (RCC) treated with the combination of MGCD516 and nivolumab. : The Secondary objective of the protocol is to capture combined results from all subjects who received treatment of the combination therapy. The intent was not to report results for each arm/group.

    Measured: From enrollment to study completion, up to 5 years 4 months

  3. Objective Response Rates (ORR)

    To estimate the objective response rates (ORR) of patients with advanced clear cell renal cell cancer (RCC) treated with the combination of MGCD516 and nivolumab. The Secondary objective of the protocol is to capture combined results from all subjects who received treatment of the combination therapy. The intent was not to report results for each arm/group.

    Measured: From enrollment to study completion, up to 5 years 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2017 (estimated)
  2. Study start23 Apr 2017
  3. Primary completion6 Sep 2022
  4. Study completion6 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03015740
Sponsor's protocol ID
2016-0332
Other IDs
NCI-2017-00324, 2016-0332
Status last verified
Oct 2024
First submitted
6 Jan 2017
Last updated
19 Nov 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Laboratory Biomarker Analysis, Nivolumab and Quality-of-Life Assessment in people with Clear Cell Renal Cell Carcinoma and Metastatic Kidney Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (time frame: from enrollment up to 12 weeks for each dosing group). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03015740.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2024.

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