Metastatic Clear Cell Renal Cell CarcinomaPhase 2NCT02781506
Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma
A Phase 2 study testing Nivolumab and SAbR in people with Metastatic Clear Cell Renal Cell Carcinoma, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Metastatic Clear Cell Renal Cell Carcinoma
- What is being tested?
- Nivolumab and SAbR
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jun 2016to 24 May 2021
- Phase
- Phase 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
Official title: Phase II Trial of Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma (mRCC)
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.
Read the detailed description
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.
- Being tested
- Nivolumab, SAbR
- Medical subject headings
- Clear-cell metastatic renal cell carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
Nivolumab IV, administered per standard of care according to institutional guidelines at the discretion of the treating medical oncologist
SAbRRadiation
Also called SBRT, Stereotactic Ablative Radiation Therapy
SAbR (1-3 lesions)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Nivolumab; Radiation: SAbR |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (10)
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.
Measured: 3 years
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2016 (estimated)
- Study start20 Jun 2016
- Primary completion24 May 2021
- Study completion24 May 2021
Why it stopped: Since the treatment landscape for metastatic kidney cancer changed, patients were not becoming eligible for this trial and therefore, the trial was terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Raquibul Hannan, University of Texas Southwestern Medical Center
- Investigators
- Raquibul Hannan, MD, PhD, Principal investigator, UT Southwestern Medical Center at Dallas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02781506
- Sponsor's protocol ID
- STU 122015-052
- Status last verified
- Jul 2022
- First submitted
- 19 May 2016
- Last updated
- 8 Aug 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Nivolumab and Stereotactic Ablative Radiation Therapy (SAbR) for Metastatic Clear Cell Renal Cell Carcinoma (mRCC)
- ClinicalTrials.gov ID
- NCT02781506
- Acronym / sponsor ID
- STU 122015-052
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Since the treatment landscape for metastatic kidney cancer changed, patients were not becoming eligible for this trial and therefore, the trial was terminated.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 20 Jun 2016 (actual)
- Primary completion
- 24 May 2021 (actual)
- Study completion
- 24 May 2021 (actual)
- First posted
- 24 May 2016 (estimated)
- Results
- Posted 8 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab and SABR | Experimental | Drug: Nivolumab, Radiation: SAbRNivolumab 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OpdivoNivolumab IV, administered per standard of care according to institutional guidelines at the discretion of the treating medical oncologist | Drug | Nivolumab and SABR |
| SAbRAlso: SBRT, Stereotactic Ablative Radiation TherapySAbR (1-3 lesions) | Radiation | Nivolumab and SABR |
Primary outcome
Response Rate (RR)
Time frame: 3 years
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.
10 secondary outcomes
Overall Survival
Time frame: 3 years
Progression Free Survival
Time frame: 3 years
Complete Response Rate
Time frame: 3 years
Time to Progression
Time frame: 3 years
Median Response Duration
Time frame: 3 years
Median Response Duration to CR (Complete Response)
Time frame: 3 years
Adverse Events
Time frame: 3 years
Health-related Quality of Life Using FACT-G Questionnaire (Functional Assessment of Cancer Therapy-General)
Time frame: Baseline and 6 months
Health-related Quality of Life Using EQ-5D (European Quality of Life Five Dimension) Questionnaire With VAS (Visual Analogue Scale)
Time frame: Baseline and 6 months
Health-related Quality of Life Using FKSI (Functional Assessment of Cancer Therapy-Kidney Symptom Index) Questionnaire
Time frame: Baseline and 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raquibul Hannan, MD, PhD principal investigator
UT Southwestern Medical Center at Dallas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and SAbR in people with Metastatic Clear Cell Renal Cell Carcinoma, run by University of Texas Southwestern Medical 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 22 inclusion and 14 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: stopped early, as of the sponsor's last update on 8 Aug 2022. 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 phase mean?
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 8 Aug 2022). 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?
Response Rate (RR) (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Aug 2022.