Stage IV Renal Cell Cancer AJCC V7Phase 2OZM-065NCT02599779
A Proof of Principle Study of Pembrolizumab With SBRT in TKI mRCC Patients
A Phase 2 study testing Pembrolizumab and Stereotactic Body Radiation Therapy in people with Stage IV Renal Cell Cancer AJCC V7, run by Sunnybrook Health Sciences Centre at 3 sites in Canada.
Trial summary
This study is designed as a phase-II proof of concept trial to investigate if a treatment strategy where stereotactic body radiation therapy (SBRT) is given with pembrolizumab is sufficiently active to warrant further investigation in randomized phase II or III studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IV Renal Cell Cancer AJCC V7
- What is being tested?
- Pembrolizumab and Stereotactic Body Radiation Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 3 sitesCanada
- Study dates
- Dec 2016to 5 Aug 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- Patients with a histologic confirmation of renal cell carcinoma with a clear cell component where the best response to first line TKI therapy (sunitinib, pazopanib, axitinib etc) is progression, or untreated RCC patients with sarcomatoid differentiation.
- Evidence of measurable metastatic kidney cancer according to RECIST 1.1 criteria. Patients should have an adequate number of non-irradiated metastatic sites in order to adequately assess the activity of the pembrolizumab therapy.
- Karnofsky performance status of ≥80.
- Favorable (0 risk factors), intermediate (1-2 risk factors) and poor risk (3-6 risk factors) patients by the Heng prognostic model are eligible based on the number of the following risk factors present.
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- Demonstrate adequate organ function, all screening labs should be performed within 10 working days of the first dose of trial treatment.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of trial treatment through 120 days after the last dose of trial treatment.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of trial treatment. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- One to three extra-cranial metastases eligible for SBRT.
Who cannot join
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has had a prior monoclonal antibody within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has more than one previous targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- Note: If subject received major surgery, they must have recovered adequately in the opinion of the investigator from the toxicity and/or complications from the intervention prior to starting trial treatment.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
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- Has known brain metastases and/or carcinomatous meningitis. Exceptions include patients who have completed treatment for brain metastases at least 3 months prior to starting treatment with pembrolizumab and remained stable and no longer require steroids to control brain edema.
- Diagnosis of ataxia telangiectasia or active collagen vascular disease.
- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
- Has evidence of interstitial lung disease, a history of non-infectious pneumonitis that required steroids, or current pneumonitis.
- Has a known active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: A Phase II Proof of Principle Study of the Activity of Pembrolizumab (MK-3475) in Combination With SBRT in Primary Tyrosine Kinase Inhibitor (TKI) Refractory Metastatic Kidney Cancer (mRCC) Patients
This study is designed as a phase-II proof of concept trial to investigate if a treatment strategy where stereotactic body radiation therapy (SBRT) is given with pembrolizumab is sufficiently active to warrant further investigation in randomized phase II or III studies. Metastatic renal cell cancer (mRCC) patients with PD-1 expressing immune cells are more likely to have larger more aggressive tumours and reduced survival and renal tumours that express PD-L1 are more aggressive with poorer outcome. Blocking this receptor/ligand interaction with monoclonal antibodies can restore the activity of tumour specific T-cells within the tumour with durable responses documented in early clinical trials in several tumour types including renal cell carcinoma. The study drug pembrolizumab is designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. SBRT will be given to the 1-3 most clinically significant lesions at the time of progression on pembrolizumab or at the 2nd course of pembrolizumab treatment in an effort to improve the activity of pembrolizumab. A total of 35 patients refractory to the approved first line therapy with a targeted drug (Sunitinib or Pazopanib) or untreated RCC patients with sarcomatoid differentiation will be enrolled on study. This group of patient has a poor outcome on any other 2nd line therapy and urgently need novel therapy.
Read the detailed description
A phase II proof of concept, multi-centre, safety and efficacy study with a biomarker component to investigate if a treatment strategy where stereotactic body radiation therapy (SBRT) is given with pembrolizumab is sufficiently active to warrant further investigation in randomized phase II or III studies. The study will run for approximately 3 years, including 2 year of recruitment and 1 year of follow up. There will be two study arms. Enrollment of 15 patients into arm A will occur before the start of enrollment of the next 20 patients on arm B.
In arm A, pembrolizumab will be started and SBRT will be given to the 1-3 most clinically significant lesions only at the time of progression on pembrolizumab. Pembrolizumab will be continued after progression to detect if the addition of SBRT leads to stability or response in progressing lesions. After SBRT, untreated measurable disease must remain to assess the activity of continued pembrolizumab. Pembrolizumab and SBRT will continue until progression as per immune related response criteria (irRC). This cohort of patients will allow us to more clearly understand if SBRT does play a part in improving progression free survival when given in combination with pembrolizumab.
In arm B, pembrolizumab will be started and SBRT given before the 2nd course of pembrolizumab to the 1-3 most clinically significant lesions. After SBRT, untreated measurable disease must remain to assess the activity of pembrolizumab. The value of a treatment strategy that combines pembrolizumab and SBRT up-front is evaluated in this arm. Giving SBRT early to the most clinically significant cancer lesions may give pembrolizumab more time to work and may improve response by generating neo-antigens.
Patients will remain on study until progression as per irRC, withdrawal of consent or if they meet any of the premature withdrawal/discontinuation criteria.
- Conditions
- Stage IV Renal Cell Cancer AJCC V7
- Being tested
- Pembrolizumab, Stereotactic Body Radiation Therapy
- Keywords
- Renal cell cancer, SBRT, Pembrolizumab
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda, MK-3475
200mg given intravenously over 30 minutes day 1 of every 3 week cycle until progression as per immune related response criteria
Stereotactic Body Radiation TherapyRadiation
Also called SBRT
Dose and duration dependent on body site. In Arm A: SBRT given at the time of progression on pembrolizumab. In Arm B: SBRT given before the 2nd course of pembrolizumab.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm A | Experimental | Arm-A: Pembrolizumab will be started and Stereotactic Body Radiation Therapy will be given at the time of progression on pembrolizumab and pembrolizumab will be continued.
Pembrolizumab will continue until progression as per immune related response criteria (irRC). Receives: Drug: Pembrolizumab; Radiation: Stereotactic Body Radiation Therapy |
| Treatment arm B | Experimental | Arm B: Pembrolizumab will be started. Stereotactic Body Radiation Therapy will be given before the 2nd course of pembrolizumab and pembrolizumab will be continued.
Pembrolizumab will continue until progression as per immune related response criteria (irRC). Receives: Drug: Pembrolizumab; Radiation: Stereotactic Body Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival, as per irRC, for pembrolizumab, given with SBRT in metastatic RCC patients where progression is the best response to their first line therapy with a TKI, and in untreated patients with sarcomatoid differentiation.
Measured: up to 36 months
Secondary outcomes (3)
Overall survival
Measured: up to 36 months
Objective response rate by immune related response criteria (irRC), and RECIST 1.1 criteria
Measured: up to 36 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Measured: up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2015 (estimated)
- Study startDec 2016
- Primary completionAug 2021
- Study completion5 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IV Renal Cell Cancer AJCC V7Studies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Ozmosis Research Inc.
- Responsible party
- Sponsor
- Investigators
- Georg Bjarnason, MD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02599779
- Sponsor's protocol ID
- OZM-065
- Acronym
- OZM-065
- Status last verified
- Aug 2021
- First submitted
- 9 Sep 2015
- Last updated
- 1 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Proof of Principle Study of the Activity of Pembrolizumab (MK-3475) in Combination With SBRT in Primary Tyrosine Kinase Inhibitor (TKI) Refractory Metastatic Kidney Cancer (mRCC) Patients
- ClinicalTrials.gov ID
- NCT02599779
- Acronym / sponsor ID
- OZM-065 / OZM-065
- Conditions
- Stage IV Renal Cell Cancer AJCC V7
- Keywords
- Renal cell cancer, SBRT, Pembrolizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Ozmosis Research Inc.
- Study start
- Dec 2016
- Primary completion
- Aug 2021 (actual)
- Study completion
- 5 Aug 2021 (actual)
- First posted
- 9 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed as a phase-II proof of concept trial to investigate if a treatment strategy where stereotactic body radiation therapy (SBRT) is given with pembrolizumab is sufficiently active to warrant further investigation in randomized phase II or III studies. Metastatic renal cell cancer (mRCC) patients with PD-1 expressing immune cells are more likely to have larger more aggressive tumours and reduced survival and renal tumours that express PD-L1 are more aggressive with poorer outcome. Blocking this receptor/ligand interaction with monoclonal antibodies can restore the activity of tumour specific T-cells within the tumour with durable responses documented in early clinical trials in several tumour types including renal cell carcinoma. The study drug pembrolizumab is designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. SBRT will be given to the 1-3 most clinically significant lesions at the time of progression on pembrolizumab or at the 2nd course of pembrolizumab treatment in an effort to improve the activity of pembrolizumab. A total of 35 patients refractory to the approved first line therapy with a targeted drug (Sunitinib or Pazopanib) or untreated RCC patients with sarcomatoid differentiation will be enrolled on study. This group of patient has a poor outcome on any other 2nd line therapy and urgently need novel therapy.
Detailed description
A phase II proof of concept, multi-centre, safety and efficacy study with a biomarker component to investigate if a treatment strategy where stereotactic body radiation therapy (SBRT) is given with pembrolizumab is sufficiently active to warrant further investigation in randomized phase II or III studies. The study will run for approximately 3 years, including 2 year of recruitment and 1 year of follow up. There will be two study arms. Enrollment of 15 patients into arm A will occur before the start of enrollment of the next 20 patients on arm B.
In arm A, pembrolizumab will be started and SBRT will be given to the 1-3 most clinically significant lesions only at the time of progression on pembrolizumab. Pembrolizumab will be continued after progression to detect if the addition of SBRT leads to stability or response in progressing lesions. After SBRT, untreated measurable disease must remain to assess the activity of continued pembrolizumab. Pembrolizumab and SBRT will continue until progression as per immune related response criteria (irRC). This cohort of patients will allow us to more clearly understand if SBRT does play a part in improving progression free survival when given in combination with pembrolizumab.
In arm B, pembrolizumab will be started and SBRT given before the 2nd course of pembrolizumab to the 1-3 most clinically significant lesions. After SBRT, untreated measurable disease must remain to assess the activity of pembrolizumab. The value of a treatment strategy that combines pembrolizumab and SBRT up-front is evaluated in this arm. Giving SBRT early to the most clinically significant cancer lesions may give pembrolizumab more time to work and may improve response by generating neo-antigens.
Patients will remain on study until progression as per irRC, withdrawal of consent or if they meet any of the premature withdrawal/discontinuation criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment arm A | Experimental | Drug: Pembrolizumab, Radiation: Stereotactic Body Radiation TherapyArm-A: Pembrolizumab will be started and Stereotactic Body Radiation Therapy will be given at the time of progression on pembrolizumab and pembrolizumab will be continued. Pembrolizumab will continue until progression as per immune related response criteria (irRC). |
| Treatment arm B | Experimental | Drug: Pembrolizumab, Radiation: Stereotactic Body Radiation TherapyArm B: Pembrolizumab will be started. Stereotactic Body Radiation Therapy will be given before the 2nd course of pembrolizumab and pembrolizumab will be continued. Pembrolizumab will continue until progression as per immune related response criteria (irRC). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Be willing and able to provide written informed consent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- Patients with a histologic confirmation of renal cell carcinoma with a clear cell component where the best response to first line TKI therapy (sunitinib, pazopanib, axitinib etc) is progression, or untreated RCC patients with sarcomatoid differentiation.
- Evidence of measurable metastatic kidney cancer according to RECIST 1.1 criteria. Patients should have an adequate number of non-irradiated metastatic sites in order to adequately assess the activity of the pembrolizumab therapy.
- Karnofsky performance status of ≥80.
Key exclusion criteria (18 listed)
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has had a prior monoclonal antibody within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has more than one previous targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- Has known brain metastases and/or carcinomatous meningitis. Exceptions include patients who have completed treatment for brain metastases at least 3 months prior to starting treatment with pembrolizumab and remained stable and no longer require steroids to control brain edema.
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 |
|---|---|---|
| PembrolizumabAlso: Keytruda, MK-3475200mg given intravenously over 30 minutes day 1 of every 3 week cycle until progression as per immune related response criteria | Drug | Treatment arm A, Treatment arm B |
| Stereotactic Body Radiation TherapyAlso: SBRTDose and duration dependent on body site. In Arm A: SBRT given at the time of progression on pembrolizumab. In Arm B: SBRT given before the 2nd course of pembrolizumab. | Radiation | Treatment arm A, Treatment arm B |
Primary outcome
Progression-free survival, as per irRC, for pembrolizumab, given with SBRT in metastatic RCC patients where progression is the best response to their first line therapy with a TKI, and in untreated patients with sarcomatoid differentiation.
Time frame: up to 36 months
3 secondary outcomes
Overall survival
Time frame: up to 36 months
Objective response rate by immune related response criteria (irRC), and RECIST 1.1 criteria
Time frame: up to 36 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time frame: up to 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2021.
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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.
Georg Bjarnason, MD principal investigator
Sunnybrook Health Sciences Centre
3 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 Pembrolizumab and Stereotactic Body Radiation Therapy in people with Stage IV Renal Cell Cancer AJCC V7, run by Sunnybrook Health Sciences Centre at 3 sites in Canada.
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 10 inclusion and 18 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 1 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Progression-free survival, as per irRC, for pembrolizumab, given with SBRT in metastatic RCC patients where progression is the best response to their first line therapy with a TKI, and in untreated patients with sarcomatoid differentiation. (time frame: up to 36 months). 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 1 Sep 2021.