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Since the treatment landscape for metastatic kidney cancer changed, patients were not becoming eligible for this trial and therefore, the trial was terminated.
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Nivolumab (brand name Opdivo): 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.
A single institution, safety lead-in phase II trial with SAbR to multiple metastatic sites concurrently administered with Nivolumab for patients with metastatic clear cell renal cell cancer who have failed at least one anti-angiogenic therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nivolumab and SABR | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nivolumab | Drug | Nivolumab IV, administered per standard of care according to institutional guidelines at the discretion of the treating medical oncologist |
|
| Measure | Description | Time Frame |
|---|---|---|
| Response Rate (RR) | 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. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | 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. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Immunological Biomarkers | 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. | 3 years |
| Cost-effectiveness |
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):
Women of child-bearing potential
Adequate Renal function with Cr ≤ 2.5 mg/dL.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Raquibul Hannan, MD, PhD | UT Southwestern Medical Center at Dallas | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Nivolumab: Nivolumab IV, administered per standard of care according to institutional guidelines at the discretion of the treating medical oncologist SAbR: SAbR (1-3 lesions) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. Nivolumab: Nivolumab IV, administered per standard of care according to institutional guidelines at the discretion of the treating medical oncologist SAbR: SAbR (1-3 lesions) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Response Rate (RR) | 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. | Posted | Number | percentage of participants | 3 years |
|
3 years
Adverse events will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0: 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
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Nivolumab: Nivolumab IV, administered per standard of care according to institutional guidelines at the discretion of the treating medical oncologist SAbR: SAbR (1-3 lesions) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Raquibul Hannan | UT Southwestern Medical Center | 214-645-8525 | Raquibul.Hannan@UTSouthwestern.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 25, 2019 | Mar 8, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C538445 | Clear-cell metastatic renal cell carcinoma |
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| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
| SAbR | Radiation | SAbR (1-3 lesions) |
|
|
| Progression Free Survival | 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. | 3 years |
| Complete Response Rate | 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. | 3 years |
| Time to Progression | 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. | 3 years |
| Median Response Duration | 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. | 3 years |
| Median Response Duration to CR (Complete Response) | To evaluate median duration, which is defined as the time between the date of CR (complete response) was first seen until date of progression. | 3 years |
| Adverse Events | 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 |
| Health-related Quality of Life Using FACT-G Questionnaire (Functional Assessment of Cancer Therapy-General) | 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. | Baseline and 6 months |
| Health-related Quality of Life Using EQ-5D (European Quality of Life Five Dimension) Questionnaire With VAS (Visual Analogue Scale) | 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. | Baseline and 6 months |
| Health-related Quality of Life Using FKSI (Functional Assessment of Cancer Therapy-Kidney Symptom Index) Questionnaire | 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. | Baseline and 6 months |
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.
| 3 years |
| Immunogenicity | 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. | 3 years |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| AJCC Stage at Diagnosis | AJCC (American Joint Committee on Cancer ) staging system is a system to describe the amount and spread of cancer in a patient's body, using TNM. T describes the size of the tumor and any spread of cancer into nearby tissue; N describes spread of cancer to nearby lymph nodes; and M describes metastasis (spread of cancer to other parts of the body) by use of x-rays, lab tests, and other tests or procedures. Stage 0: Abnormal cells are present but have not spread to nearby tissue; Stage I-III: Cancer is present; Stage IV: The cancer has spread to distant parts of the body. | Number | number of participants |
|
|
|
| Secondary | Overall Survival | 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. | Posted | Number | percentage of participants | 3 years |
|
|
|
| Secondary | Progression Free Survival | 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. | Posted | Median | Full Range | months | 3 years |
|
|
|
| Secondary | Complete Response Rate | 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. | Posted | Count of Participants | Participants | 3 years |
|
|
|
| Secondary | Time to Progression | 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. | Posted | Median | Full Range | months | 3 years |
|
|
|
| Secondary | Median Response Duration | 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. | Posted | Median | Full Range | weeks | 3 years |
|
|
|
| Secondary | Median Response Duration to CR (Complete Response) | To evaluate median duration, which is defined as the time between the date of CR (complete response) was first seen until date of progression. | No patient achieved complete response (CR). | Posted | 3 years |
|
|
| Secondary | Adverse Events | 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 | Posted | Number | events | 3 years |
|
|
|
| Secondary | Health-related Quality of Life Using FACT-G Questionnaire (Functional Assessment of Cancer Therapy-General) | 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. | Posted | Median | Full Range | score on scale | Baseline and 6 months |
|
|
|
| Secondary | Health-related Quality of Life Using EQ-5D (European Quality of Life Five Dimension) Questionnaire With VAS (Visual Analogue Scale) | 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. | Posted | Median | Full Range | score on a scale | Baseline and 6 months |
|
|
|
| Secondary | Health-related Quality of Life Using FKSI (Functional Assessment of Cancer Therapy-Kidney Symptom Index) Questionnaire | 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. | Posted | Median | Full Range | score on a scale | Baseline and 6 months |
|
|
|
| Other Pre-specified | Immunological Biomarkers | 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. | Not Posted | 3 years | Participants |
| Other Pre-specified | Cost-effectiveness | 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. | Not Posted | 3 years | Participants |
| Other Pre-specified | Immunogenicity | 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. | Not Posted | 3 years | Participants |
| 1 |
| 7 |
| 0 |
| 7 |
| 7 |
| 7 |
| Genitourinary | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hematologic | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Musculoskeletal | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Renal/Electrolyte | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Respiratory | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Skin | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
Not provided
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Not provided
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Title | Measurements |
|---|---|
|
| 6 month follow up Self-Care |
|
| Baseline Usual Activities |
|
| 6 month follow up Usual Activities |
|
| Baseline Pain/Discomfort |
|
| 6 month follow up Pain/Discomfort |
|
| Baseline Anxiety/Depression |
|
| 6 month follow up Anxiety/Depression |
|
| Baseline EQ-VAS |
|
| 6 month follow up EQ-VAS |
|