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Study of Nivolumab and Axitinib in Patients With Advanced Renal Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT03172754
Recruitment Status : Recruiting
First Posted : June 1, 2017
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
Fox Chase Cancer Center

Tracking Information
First Submitted Date  ICMJE April 11, 2017
First Posted Date  ICMJE June 1, 2017
Last Update Posted Date August 26, 2019
Actual Study Start Date  ICMJE June 12, 2017
Estimated Primary Completion Date April 6, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2017)
  • Incidence of treatment-related adverse events [ Time Frame: Up to 15 months ]
    To be assessed by CTCAE v4.03. Will be used to establish recommended phase II dose (RP2D)
  • Overall response rate (ORR) [ Time Frame: Up to 12 months ]
    To be assessed by RECIST 1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03172754 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2017)
  • Duration of response (DOR) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 weeks ]
    DOR is the time from first partial response or complete response until progressive disease as assessed by RECIST 1.1
  • Progression free survival (PFS) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 weeks ]
    PFS is the time from initiation of treatment to confirmed disease progression per RECIST 1.1
  • Overall survival (OS) [ Time Frame: From date of initiation of treatment to death or when the patient is lost to follow up, approximately 25 months on average ]
    OS is the time from initiation of treatment to death or when the patient is lost to follow up
  • Safety profile as assessed by CTCAE 4.03 [ Time Frame: Up to 15 months ]
    Summarized by type, frequency, and severity
  • PD-L1 expression on tumor biospecimens [ Time Frame: Up to 12 months ]
    Descriptive statistics from analysis of patient samples
  • Tumor infiltrating lymphocyte assessments on tumor biospecimens [ Time Frame: Up to 12 months ]
    Descriptive statistics from analysis of patient samples
  • Pharmacodynamic effect of study treatment including cytokines [ Time Frame: Up to 12 months ]
    Descriptive statistics from analysis of patient samples
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Nivolumab and Axitinib in Patients With Advanced Renal Cell Carcinoma
Official Title  ICMJE Phase I/II Study of Nivolumab and Axitinib in Patients With Advanced Renal Cell Carcinoma
Brief Summary This is a Phase I/II, open-label, multi-center study of axitinib in combination with nivolumab in patients with previously treated and untreated advanced RCC. This clinical study will be composed of a dose finding phase (Phase I) and two parallel dose expansion phases (Phase II). The dose finding phase will assess the safety of the combination and establish a recommended phase II dose (RP2D, the highest tested dose that is declared safe and tolerable by the Investigators and the Sponsor Investigator) in patients with advanced RCC who have received prior systemic therapy for metastatic disease. Phase II will evaluate the efficacy of the combination at the RP2D in two parallel expansion cohorts in both previously treated and treatment naïve patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Renal Cell Carcinoma
Intervention  ICMJE
  • Drug: Nivolumab
    PD-1 inhibitor
  • Drug: Axitinib
    Tyrosine kinase inhibitor
Study Arms  ICMJE
  • Experimental: Phase I patients
    Phase I patients must have received at least 1 prior tyrosine kinase inhibitor for RCC.
    Interventions:
    • Drug: Nivolumab
    • Drug: Axitinib
  • Experimental: Phase II patients: cohort 1
    Phase II cohort 1 patients must have received at least 1 prior tyrosine kinase inhibitor for RCC.
    Interventions:
    • Drug: Nivolumab
    • Drug: Axitinib
  • Experimental: Phase II patients: cohort 2
    Phase II cohort 2 patients must not have received prior systemic therapy for advanced RCC.
    Interventions:
    • Drug: Nivolumab
    • Drug: Axitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 30, 2017)
98
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 6, 2024
Estimated Primary Completion Date April 6, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed advanced RCC with predominantly clear cell subtype.
  • Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study.
  • Formalin fixed, paraffin embedded [FFPE] tissue block(s) or at least 12 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.
  • At least one measureable lesion as defined by RECIST version 1.1.
  • Age > 18 years.
  • ECOG performance status 0 or 1
  • Adequate bone marrow, kidney, and liver function as defined by: WBC ≥ 2000/μL. Neutrophils ≥ 1500/μL. Platelets ≥ 100 x103/μL. Hemoglobin > 9.0 g/dL. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula): Female CrCl = (140 - age in years) x (weight in kg x 0.85)/(72 x serum creatinine in mg/dL). Male CrCl = (140 - age in years) x (weight in kg x 1.00)/(72 x serum creatinine in mg/dL). AST/ALT ≤ 3 x ULN. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL).
  • No evidence of pre-existing uncontrolled hypertension as documented by 2 baseline blood pressure (BP) readings taken at least 1 hour apart. The baseline systolic BP readings must be ≤ 150 mm Hg, and the baseline diastolic BP readings must be ≤ 90 mm Hg
  • Patients enrolled to the prior treatment arm of the expansion cohort must have been exposed to a TKI for metastatic disease. Exposure to TKI as part of (neo)adjuvant treatment that completed within 1 year of study qualifies as prior exposure as well.

Exclusion Criteria:

  • Prior therapy with axitinib
  • Prior systemic therapy directed at advanced RCC is not allowed for patients enrolled to the expansion cohort, treatment naïve arm. If prior (neo)adjuvant treatment given as part of a clinical trial, this would be allowed as long as last dose was > 1 year prior to start of treatment
  • Patients enrolled to the prior treatment arm of the dose escalation cohort must not have received anti-cancer therapy less than 14 days prior to the first dose of study drug or palliative, focal radiation therapy less than 14 days prior to the first dose of study drug.
  • Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Patients are excluded if they have active, symptomatic brain metastases or leptomeningeal metastases. Subjects with known brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for four weeks (after treatment is complete and within 28 days prior to study drug administration.
  • Second malignancy requiring active systemic treatment
  • Diagnosis of immunodeficiency
  • Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Patients have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Major surgery <4 weeks or radiation therapy <2 weeks of study entry. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
  • Gastrointestinal abnormalities including: Inability to take oral medication; Requirement for intravenous alimentation; Prior surgical procedures affecting absorption including total gastric resection; Treatment for active peptic ulcer disease in the past 6 months; Active gastrointestinal bleeding as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy; Malabsorption syndromes.
  • Evidence of inadequate wound healing.
  • Active bleeding disorder or other history of significant bleeding episodes within 30 days before study entry.
  • Known prior or suspected hypersensitivity to study drugs or any component in their formulations.
  • Current use or anticipated need for treatment with drugs or foods that are known strong CYP3A4/5 inhibitors including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice. The topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed.
  • Current use or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.
  • As there is potential for hepatic toxicity with nivolumab, drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen.
  • Known hepatitis B virus (HBV) or hepatitis C virus (HBV) infection.
  • Known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • History of any of the following cardiovascular conditions within 12 months of screening: Myocardial infarction, Unstable angina pectoris, Cardiac angioplasty or stenting, Coronary/peripheral artery bypass graft, Class III or IV congestive heart failure per New York Heart Association, Cerebrovascular accident or transient ischemic attack
  • History of deep vein thrombosis or pulmonary embolism within 6 months of screening. Patients who are currently taking anticoagulation therapy for a prior history (> 6 months from screening) of thrombosis may still be eligible.
  • Pregnant or breast feeding.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Matthew Zibelman, MD 215-214-1515 matthew.zibelman@fccc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03172754
Other Study ID Numbers  ICMJE GU-102
17-1009 ( Other Identifier: Fox Chase Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fox Chase Cancer Center
Study Sponsor  ICMJE Fox Chase Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Fox Chase Cancer Center
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP