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- Klinische proef NCT02781506
Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma
Phase II Trial of Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma (mRCC)
Studie Overzicht
Toestand
Interventie / Behandeling
Gedetailleerde beschrijving
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
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Texas
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Dallas, Texas, Verenigde Staten, 75390
- University of Texas Southwestern Medical Center
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- At least 18 years of age
- Willing and able to provide consent
- Pathologic diagnosis of metastatic RCC with clear cell component
- Measurable disease in at least 2 non-radiated sites. Progression or intolerance to at least one prior systemic anti-angiogenic therapy.
- Eligible for extra-CNS SAbR to 1-6 sites of disease
- Must have received at least one prior anti-angiogenic therapy in the advanced or metastatic setting. Prior cytokine therapy (eg, IL-2, IFN-α), vaccine therapy, or treatment with cytotoxic therapy is also allowed but not any other drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Previous treatment with surgery, radiation, chemotherapy, targeted agents (see above) are allowed provided that: Chemotherapy/Major surgery was administered > 14 days before the start Nivolumab; Minor surgery, radiation, or any targeted agents were administered > 7 days before the start of Nivolumab
- Performance status ECOG 0, 1, 2 or 3.
Adequate organ and marrow function as defined below (obtained within 14 days of first dose of drug):
- leukocytes≥ 2,000/mcL
- absolute neutrophil count ≥ 1,500/mcL
- platelets ≥ 50,000/mcl
- total bilirubin ≤ 2mg/dL
- AST(SGOT)/ALT(SPGT) ≤ 3 X institutional upper limit of normal
Women of child-bearing potential
- female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- must have a negative serum or urine pregnancy test within 24 hours prior to the start of investigational product.
- Women must not be breastfeeding.
- must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and contraception should be continued for a period of 30 days plus the time required for the investigational drug to undergo five half lives.
- Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Contraception should be continued for a period of 90 days plus the time required for the investigational drug to undergo five half lives. This is equivalent to 31 weeks after discontinuation of Nivolumab.
- Adequate Renal function with Cr ≤ 2.5 mg/dL.
Exclusion Criteria:
- Subjects who have had major surgery (such as nephrectomy) or chemotherapy within 2 weeks prior to first dose of drug
- Subjects who have had radiation therapy within 2 weeks prior to first dose of drug
- Uncontrolled adrenal insufficiency or active chronic liver disease
- Any history of CNS metastases that is not adequately treated with surgery or SABR >14 days prior.
- Prior treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Any positive history for HIV/AIDS, HTLV, hepatitis B or hepatitis C virus indicating acute or chronic infection.
- Any active known or suspected autoimmune disease. Subjects with 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 are permitted to enroll.
- Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalent are permitted (although not encouraged) in the absence of active autoimmune disease.
- Subjects with life expectancy < 6 months
- Subjects receiving any other investigational or standard antineoplastic agents.
- Prior malignancies active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, breast?, or etc.
- Psychiatric illness/social situations that would limit consenting and compliance with study requirements.
- Patients with history of hypersensitivity to monoclonal antibodies
- Subjects who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Nivolumab and SABR
Nivolumab alone: IV, administered per standard of care according to institutional guidelines at the discretion of the treating medical oncologist, until disease progression or unacceptable toxicity.
SABR, dose variable, in 1-3 fractions.
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Nivolumab IV, administered per standard of care according to institutional guidelines at the discretion of the treating medical oncologist
Andere namen:
SAbR (1-3 lesions)
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Response Rate (RR)
Tijdsspanne: 3 years
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The primary objective of the randomized phase II trial will be to increase the RR (response rate) of treatment with Nivolumab by the concurrent administration of SAbR.
The assessment of RR will be based on the evaluation of ir-RECIST (Response Evaluation Criteria in Solid Tumors) criteria and radiated lesions will be excluded from target lesions.
Treatment response will be measured using both the RECIST and immune related RECIST criteria (ir-RECIST), a minor modification of RECIST 1.1 for immunotherapy.
Radiated lesions will be excluded from target lesions.
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3 years
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
Overall Survival
Tijdsspanne: 3 years
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To evaluate the overall survival (OS), which is defined as the time between date of registration and the date of death due to any cause.
In analyzing OS, we will take into account the MSKCC (Memorial Sloan Kettering Cancer Center) prognostic criteria for mRCC (Metastatic Renal Cell Carcinoma) and compare our data to historical controls in the appropriate risk category.
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3 years
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Progression Free Survival
Tijdsspanne: 3 years
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To evaluate progression free survival (PFS), which is defined as the time between date of registration and the first date of documented disease progression or date of death due to any cause.
Progression will be defined according to the ir-RECIST (Response Evaluation Criteria in Solid Tumors) criteria and verified by a second set of imaging at least 6 weeks apart.
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3 years
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Complete Response Rate
Tijdsspanne: 3 years
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To evaluate and compare complete response rate in each arm, which is defined as the percentage of patients who show complete response as per ir-RECIST (Response Evaluation Criteria in Solid Tumours) criteria.
Treatment response will be measured using both the RECIST and immune related RECIST criteria (ir-RECIST), a minor modification of RECIST 1.1 for immunotherapy.
Radiated lesions will be excluded from target lesions.
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3 years
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Time to Progression
Tijdsspanne: 3 years
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To evaluate and compare time to progression (TTP), which is defined as time between date of registration and date of documented progression, between the experimental and control arms.
Progression will be defined according to the ir-RECIST (Response Evaluation Criteria in Solid Tumors) criteria and verified by a second set of imaging at least 6 weeks apart.
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3 years
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Median Response Duration
Tijdsspanne: 3 years
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To evaluate median response duration, which is defined as the time between the date of PR (partial response) was first seen until date of progression.
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3 years
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Median Response Duration to CR (Complete Response)
Tijdsspanne: 3 years
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To evaluate median duration, which is defined as the time between the date of CR (complete response) was first seen until date of progression.
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3 years
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Adverse Events
Tijdsspanne: 3 years
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To evaluate the tolerability and toxicity as measured according to CTCAE v4.0. Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) and version number 4.0. Adverse events not specifically defined in the NCI CTCAE will be scored on the Adverse Event log according to the general guidelines provided by the NCI CTCAE and as outlined below. Grade 1: Mild Grade 2: Moderate Grade 3: Severe or medically significant but not immediately life threatening Grade 4: Life threatening consequences Grade 5: Death related to the adverse event |
3 years
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Health-related Quality of Life Using FACT-G Questionnaire (Functional Assessment of Cancer Therapy-General)
Tijdsspanne: Baseline and 6 months
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FACT-G is a measure that sums the functional well being (FWB), physical well being (PWB), the social/family well-being (S/FWB), and emotional well being (EMB) using a 5-point Likert-type response choices (0 = not at all; 1 = a little bit; 2 =somewhat; 3 = quite a bit; 4 = very much).
Questions are phrased so that higher numbers indicate a better health state, leading to some items being reverse-scored.
Scoring the FACT-G is performed through a simple sum of item scores with a total possible score of 105.
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Baseline and 6 months
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Health-related Quality of Life Using EQ-5D (European Quality of Life Five Dimension) Questionnaire With VAS (Visual Analogue Scale)
Tijdsspanne: Baseline and 6 months
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EQ-5D is a standardized participant completed questionnaire consisted of 2 components: a health state profile and VAS.
EQ-5D health state profile had 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression.
Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems.
Responses to 5 dimensions comprised a health state/a single utility index value.
Every health state (coded as combination of responses on each of 5 dimensions) had a unique predefined utility index value assigned to it, by EuroQol.
US value sets (with all possible health states) was used for adults in the study, range from 1 to -0.109.
Higher (positive) scores = better health state.
VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state.
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Baseline and 6 months
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Health-related Quality of Life Using FKSI (Functional Assessment of Cancer Therapy-Kidney Symptom Index) Questionnaire
Tijdsspanne: Baseline and 6 months
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The FKSI is a 15 question validated symptom index for kidney cancer patients.
This scale focuses on symptoms predominantly related to kidney cancer such as energy, fatigue, pain, bone pain, weight loss, shortness of breath, cough, fever, hematuria.
Each item was scored on a 5-point scale (0=not at all to 4=very much).
FKSI total score ranged from 0 (most severe symptoms) to 60 (no symptoms) with a higher score indicating a better outcome.
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Baseline and 6 months
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Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Immunological Biomarkers
Tijdsspanne: 3 years
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To identify immunological biomarkers as predictors of treatment response or resistance.
This is an exploratory outcome and was added as a secondary outcome in error.
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3 years
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Cost-effectiveness
Tijdsspanne: 3 years
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To evaluate the cost-effectiveness and cost-utility of the addition of SAbR to Nivolumab in patients with mRCC.
This is an exploratory outcome and was added as a secondary outcome in error.
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3 years
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Immunogenicity
Tijdsspanne: 3 years
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To measure and compare treatment-related tumor-specific immune response (immunogenicity) in each arm.
This is an exploratory outcome and was added as a secondary outcome in error.
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3 years
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Medewerkers en onderzoekers
Onderzoekers
- Hoofdonderzoeker: Raquibul Hannan, MD, PhD, UT Southwestern Medical Center at Dallas
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata per histologisch type
- Neoplasmata
- Urologische neoplasmata
- Urogenitale neoplasmata
- Neoplasmata per site
- Nier Ziekten
- Urologische ziekten
- Adenocarcinoom
- Neoplasmata, glandulair en epitheel
- Nierneoplasmata
- Carcinoom, niercel
- Carcinoom
- Moleculaire mechanismen van farmacologische werking
- Antineoplastische middelen
- Antineoplastische middelen, immunologisch
- Immuun Checkpoint-remmers
- Nivolumab
Andere studie-ID-nummers
- STU 122015-052
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
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