Kidney Cancer MetastaticPhase 2RADVAXNCT03065179
SBRT (Stereotactic Body Radiation Therapy) in Combination With Nivolumab/Ipilimumab in Renal Cell Carcinoma (RCC) / Kidney Cancer Patients
A Phase 2 study testing Nivolumab/Ipilimumab and SBRT in people with Kidney Cancer Metastatic and Kidney Cancer, run by University of Texas Southwestern Medical Center at 2 sites in United States.
Trial summary
This is a multi-institution, single-arm phase II study to determine the safety and efficacy of SBRT (up to 2 metastatic sites preferentially lung, mediastinum or bone in combination of nivolumab and ipilimumab in patients with metastatic renal cell carcinoma(with a clear-cell component and at least 1 measurable… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Kidney Cancer Metastatic, Kidney Cancer, Kidney Cancer, Stage IV
- What is being tested?
- Nivolumab/Ipilimumab and SBRT
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Mar 2017to 17 Nov 2020
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histological confirmation of RCC with a clear-cell component
- Metastatic (AJCC Stage IV) RCC
- Prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is allowed provided recurrence occurred = or > 6 months after the last dose of the adjuvant or neoadjuvant therapy
- Any number of prior systemic treatment regimen in the advanced/metastatic setting is allowed (cytokine, anti-angiogenic, mammalian target of rapamycin (mTOR) inhibitor or clinical trial) including previously untreated patients
- Karnofsky Performance Status (KPS) of at least 70%
- Life expectancy of at least 3 months
Show all 9Show fewer
- At least 2 metastatic sites of which at least 1 must be measurable as per RECIST 1.1
- Archival Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for correlative studies (Note: Fine Needle Aspiration (FNA) and bone metastases samples are not acceptable for submission)
- Patients with favorable, intermediate and poor risk categories will be eligible for the study. Patients must be categorized according to favorable versus intermediate/poor risk status at registration. International Metastatic RCC Database Consortium (IMDC) must be used to determine prognostic factors
Who cannot join
- Subjects with previously treated brain or CNS (Central nervous system) metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery was completed at least 2 weeks prior to study drug administration. Liver metastases will not be included as part of the radiated lesions to be treated.
- Medical History and Concurrent Diseases:
- Prior treatment with an anti-Programmed cell death(PD) -1, anti-PD-L1, anti-PD-L2, anti-CD137(cluster of differentiation), or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein ) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Prior treatment with high dose interleukin (HD IL)-2 is allowed.
- Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll. Patients with psoriasis not requiring active, systemic treatment are allowed.
- Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- Uncontrolled adrenal insufficiency
Show all 28Show fewer
- Requirement for anti-coagulation with Coumadin, low molecular weight heparin and anti-thrombin inhibitors will be accepted if anticoagulation has been stable for at least 4 weeks and no recent history of prior bleeding complications.
- Prior malignancy 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 cervix, breast or low risk Gleason 6 prostate cancer
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection
- Known medical condition (eg, a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
- Major surgery (eg, nephrectomy) less than 28 days prior to the first dose of study drug
- 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
- Presence of any toxicities attributed to prior anti-cancer therapy, other than alopecia, that have not resolved to Grade 1 (NCI CTCAE v4) or baseline before administration of study drug
- Physical and Laboratory Test Findings:
- Any of the following laboratory test findings:
- White blood cell (WBC) < 2,000/mm3
- Neutrophils < 1,500/mm3
- Platelets < 100,000/mm3
- aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x ULN (> 5 x ULN if liver metastases are present)
- Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
- Serum creatinine > 1.5 x upper limit of normal (ULN) or creatinine clearance < 40 mL/min (measured or calculated by Cockroft-Gault formula)
- Allergies and Adverse Drug Reaction:
- History of severe hypersensitivity reaction to any monoclonal antibody or study drug components
- Other Exclusion Criteria:
- Prisoners or subject who are involuntarily incarcerated
- Not suitable for SBRT treatment
- Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287
UT Southwestern
Dallas, Texas, 75390
About this study
Official title: Phase II Trial of Stereotactic Body Radiation Therapy in Combination With Nivolumab Plus Ipilimumab in Patients With Metastatic Renal Cell Cancer
This is a multi-institution, single-arm phase II study to determine the safety and efficacy of SBRT (up to 2 metastatic sites preferentially lung, mediastinum or bone in combination of nivolumab and ipilimumab in patients with metastatic renal cell carcinoma(with a clear-cell component and at least 1 measurable metastatic lesion that is not being irradiated).
Read the detailed description
The study is planned based on a two-stage design that allows early termination for lack of efficacy. A safety run-in phase will be included comprising the first 6 patients at minimum to ensure that the combination of nivolumab plus ipilimumab and SBRT is safe. Then, the investigators will determine whether the combination of nivolumab plus ipilimumab and SBRT yields a clinically compelling antitumor activity measured as objective response rate (ORR), and evaluate other endpoints including Thrombotic thrombocytopenic purpura (TTP), duration of response (DOR), progression free survival (PFS), overall survival (OS) and local control of irradiated sites.
There is no previous experience with SBRT used concurrently with nivolumab and ipilimumab in this study population. Therefore, to ensure that the combination is safe, the first six patients will be treated and observed for toxicity for 6 weeks after radiation before continuing with further accrual. Therefore, six patients will be enrolled at the proposed dose of nivolumab and ipilimumab in combination with SBRT. If 4 out of the first 6 patients experience Grade 3/4 toxicity or a lower grade toxicity requiring immune suppressive therapy during the safety run-in observation period (defined as the first 4-cycles, 12 weeks), enrollment will cease and the study will be halted until further safety analysis of the combination regimen can be performed. If less than 4 out of the first 6 patients experience Grade 3/4 toxicities or require steroids, the investigators will proceed with additional accrual with this regimen.
- Being tested
- Nivolumab/Ipilimumab, SBRT
- Medical subject headings
- Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab/IpilimumabDrug
Also called Opdivo, Yervoy
IV immunotherapy
SBRTRadiation
Also called stereotactic radiation
SBRT will be delivered in conjunction with immunotherapy
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab/Ipilimumab plus SBRT | Experimental | Induction Dual Immune Checkpoint Inhibition with nivolumab and ipilimumab plus SBRT to 1-2 metastatic sites, followed by nivolumab monotherapy Receives: Drug: Nivolumab/Ipilimumab; Radiation: SBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-related Adverse Events Grade 3 or Higher as Assessed by CTCAE v4.0
An adverse event (AE) will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Measured: up to 35 months
Number of Participants Needing Corticosteroids
Measured: up to 35 months
Objective Response Rate (ORR)
The ORR is defined as the number of participants with a BOR of CR (Complete response) or PR (Partial response) divided by the number of treated participants. The BOR (Best overall response) is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy including radiotherapy, tumor-directed surgery, or systemic anticancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment
Measured: up to 35 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2017
- Study start1 Mar 2017
- Primary completion20 Feb 2020
- Study completion17 Nov 2020
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 Kidney Cancer MetastaticStudies 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
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hans Hammers, University of Texas Southwestern Medical Center
- Investigators
- Hans Hammers, MD, PhD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03065179
- Sponsor's protocol ID
- STU 072016-044
- Acronym
- RADVAX
- Status last verified
- Mar 2021
- First submitted
- 7 Feb 2017
- Last updated
- 30 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Stereotactic Body Radiation Therapy in Combination With Nivolumab Plus Ipilimumab in Patients With Metastatic Renal Cell Cancer
- ClinicalTrials.gov ID
- NCT03065179
- Acronym / sponsor ID
- RADVAX / STU 072016-044
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 20 Feb 2020 (actual)
- Study completion
- 17 Nov 2020 (actual)
- First posted
- 27 Feb 2017 (actual)
- Results
- Posted 30 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-institution, single-arm phase II study to determine the safety and efficacy of SBRT (up to 2 metastatic sites preferentially lung, mediastinum or bone in combination of nivolumab and ipilimumab in patients with metastatic renal cell carcinoma(with a clear-cell component and at least 1 measurable metastatic lesion that is not being irradiated).
Detailed description
The study is planned based on a two-stage design that allows early termination for lack of efficacy. A safety run-in phase will be included comprising the first 6 patients at minimum to ensure that the combination of nivolumab plus ipilimumab and SBRT is safe. Then, the investigators will determine whether the combination of nivolumab plus ipilimumab and SBRT yields a clinically compelling antitumor activity measured as objective response rate (ORR), and evaluate other endpoints including Thrombotic thrombocytopenic purpura (TTP), duration of response (DOR), progression free survival (PFS), overall survival (OS) and local control of irradiated sites.
There is no previous experience with SBRT used concurrently with nivolumab and ipilimumab in this study population. Therefore, to ensure that the combination is safe, the first six patients will be treated and observed for toxicity for 6 weeks after radiation before continuing with further accrual. Therefore, six patients will be enrolled at the proposed dose of nivolumab and ipilimumab in combination with SBRT. If 4 out of the first 6 patients experience Grade 3/4 toxicity or a lower grade toxicity requiring immune suppressive therapy during the safety run-in observation period (defined as the first 4-cycles, 12 weeks), enrollment will cease and the study will be halted until further safety analysis of the combination regimen can be performed. If less than 4 out of the first 6 patients experience Grade 3/4 toxicities or require steroids, the investigators will proceed with additional accrual with this regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab/Ipilimumab plus SBRT | Experimental | Drug: Nivolumab/Ipilimumab, Radiation: SBRTInduction Dual Immune Checkpoint Inhibition with nivolumab and ipilimumab plus SBRT to 1-2 metastatic sites, followed by nivolumab monotherapy |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Histological confirmation of RCC with a clear-cell component
- Metastatic (AJCC Stage IV) RCC
- Prior adjuvant or neoadjuvant therapy for localized or locally advanced RCC is allowed provided recurrence occurred = or > 6 months after the last dose of the adjuvant or neoadjuvant therapy
- Any number of prior systemic treatment regimen in the advanced/metastatic setting is allowed (cytokine, anti-angiogenic, mammalian target of rapamycin (mTOR) inhibitor or clinical trial) including previously untreated patients
- Karnofsky Performance Status (KPS) of at least 70%
Key exclusion criteria (28 listed)
- Subjects with previously treated brain or CNS (Central nervous system) metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy and is not requiring steroids, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery was completed at least 2 weeks prior to study drug administration. Liver metastases will not be included as part of the radiated lesions to be treated.
- Prior treatment with an anti-Programmed cell death(PD) -1, anti-PD-L1, anti-PD-L2, anti-CD137(cluster of differentiation), or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein ) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. Prior treatment with high dose interleukin (HD IL)-2 is allowed.
- Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll. Patients with psoriasis not requiring active, systemic treatment are allowed.
- Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
- Uncontrolled adrenal insufficiency
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 |
|---|---|---|
| Nivolumab/IpilimumabAlso: Opdivo, YervoyIV immunotherapy | Drug | Nivolumab/Ipilimumab plus SBRT |
| SBRTAlso: stereotactic radiationSBRT will be delivered in conjunction with immunotherapy | Radiation | Nivolumab/Ipilimumab plus SBRT |
Primary outcome
Number of Participants With Treatment-related Adverse Events Grade 3 or Higher as Assessed by CTCAE v4.0
Time frame: up to 35 months
An adverse event (AE) will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Number of Participants Needing Corticosteroids
Time frame: up to 35 months
Objective Response Rate (ORR)
Time frame: up to 35 months
The ORR is defined as the number of participants with a BOR of CR (Complete response) or PR (Partial response) divided by the number of treated participants. The BOR (Best overall response) is defined as the best response designation, as determined by the investigator, recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of first subsequent anti-cancer therapy including radiotherapy, tumor-directed surgery, or systemic anticancer therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2021.
- 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.
Hans Hammers, MD, PhD principal investigator
University of Texas Southwestern Medical Center
2 sites 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/Ipilimumab and SBRT in people with Kidney Cancer Metastatic and Kidney Cancer, run by University of Texas Southwestern Medical Center at 2 sites 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 9 inclusion and 28 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: finished, as of the sponsor's last update on 30 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 30 Mar 2021). 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?
Number of Participants With Treatment-related Adverse Events Grade 3 or Higher as Assessed by CTCAE v4.0 (time frame: up to 35 months). The study lists 3 primary outcomes in all. 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 30 Mar 2021.