Study of Nivolumab and Axitinib in Patients With Advanced Renal Cell Carcinoma
|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.|
|ClinicalTrials.gov Identifier: NCT03172754|
Recruitment Status : Recruiting
First Posted : June 1, 2017
Last Update Posted : May 16, 2023
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Renal Cell Carcinoma||Drug: Nivolumab Drug: Axitinib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||98 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of Nivolumab and Axitinib in Patients With Advanced Renal Cell Carcinoma|
|Actual Study Start Date :||June 12, 2017|
|Estimated Primary Completion Date :||April 6, 2024|
|Estimated Study Completion Date :||April 6, 2025|
Experimental: Phase I patients
Phase I patients must have received at least 1 prior tyrosine kinase inhibitor for RCC.
Tyrosine kinase inhibitor
Experimental: Phase II patients: cohort 1
Phase II cohort 1 patients must have received at least 1 prior tyrosine kinase inhibitor for RCC.
Tyrosine kinase inhibitor
Experimental: Phase II patients: cohort 2
Phase II cohort 2 patients must not have received prior systemic therapy for advanced RCC.
Tyrosine kinase inhibitor
- 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
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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 measurable 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 OR treated with the combination of ipilimumab and nivolumab in the 1st line setting 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. Prior high dose interleukin-2 is allowed and patients who received this as their only prior line of treatment for metastatic disease may be included in the treatment naïve group.
- 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.
- 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.
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 ClinicalTrials.gov identifier (NCT number): NCT03172754
|Contact: Matthew Zibelman, MDfirstname.lastname@example.org|
|United States, Maryland|
|Baltimore, Maryland, United States, 21231|
|Contact: Michael Carducci, MD 410-955-8893 email@example.com|
|United States, New York|
|US Oncology and Hematology||Recruiting|
|Albany, New York, United States, 12206|
|Contact: Rahul Ravilla, MD|
|Principal Investigator: Rahul Ravilla, MD|
|New York, New York, United States, 10021|
|Contact: Ana Molina, MD 646-968-2072 firstname.lastname@example.org|
|United States, Pennsylvania|
|Fox Chase Cancer Center||Recruiting|
|Philadelphia, Pennsylvania, United States, 19111|
|Contact: Matthew Zibelman, MD 215-214-1515 email@example.com|
Documents provided by Fox Chase Cancer Center:
|Responsible Party:||Fox Chase Cancer Center|
|Other Study ID Numbers:||
17-1009 ( Other Identifier: Fox Chase Cancer Center )
|First Posted:||June 1, 2017 Key Record Dates|
|Last Update Posted:||May 16, 2023|
|Last Verified:||May 2023|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Male Urogenital Diseases
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors