Solid TumorPhase 2NCT03220854
SBRT + PD-1/PDL-1 Inhibiting Therapy for Advanced Solid Tumors After Dz Control on PD-1/PDL-1 Tx
A Phase 2 study testing Stereotactic radiotherapy, Biological: humanized anti-PD-1 monoclonal antibody and Biological: humanized anti-PD-L1 monoclonal antibody in people with Solid Tumor, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
The purpose of this study is to find out if having radiation therapy and continuing immunotherapy can improve the benefit of immunotherapy. There have been reports of patients who were treated with radiation therapy that not only caused the treated tumors to shrink or stop growing, but also resulted in tumors that had… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- Stereotactic radiotherapy, Biological: humanized anti-PD-1 monoclonal antibody and Biological: humanized anti-PD-L1 monoclonal antibody
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2017to 22 Sep 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically-proven diagnosis of a solid tumor malignancy
- One of the following criteria must be met:
- Clinical or radiographic evidence of disease control (defined as best response of stable disease (SD) or partial response (PR) or combination of both for ≥ 16 weeks) without evidence of complete response (CR) or progression OR
- Clinical or radiographic evidence of disease progression during treatment with PD-1 or PD-L1 inhibiting therapy, following previous tumor response (CR, PR, or SD for ≥ 16 weeks) to PD-1 or PD-L1 inhibiting therapy, and, for patients who discontinued PD-1 or PD-L1 inhibiting therapy during response to therapy, disease progression must have occurred following at least 8 weeks of re-treatment with PD-1 or PD-L1 inhibiting therapy Note: Both the treating medical oncologist and radiation oncologist must be in agreement with determination of disease progression.
- Administration of a PD-1 or PD-L1 inhibitor within 60 days prior to study registration
- Determination by the treating radiation oncologist that the patient is a candidate for SRT (ie, radiation therapy with a stereotactic setup) Note: All brain metastases will receive stereotactic radiotherapy (SRT).
Show all 13Show fewer
- The total number of tumors requiring SRT must be ≤ 5 Note: Regardless of the number of brain metastases that will be treated with SRT, the brain metastases will be considered to be one tumor.
- Measurable disease by RECIST v1.1 that will not undergo SRT and that is amenable to monitoring Note: all brain metastases will receive SRT. Therefore, a patient with brain metastases that will be treated with SRT must also have extracranial disease that will not undergo SRT and that is amenable to monitoring
- Determination by the treating medical oncologist that the patient is a candidate to continue the PD-1 or PD-L1 inhibiting therapy that had previously provided disease control
- Age ≥ 18 years
- Karnofsky Performance Status score of ≥ 60 %
- A woman of childbearing potential (WCBP), defined as a woman who is < 60 years of age and has not had a hysterectomy, must have a documented negative serum pregnancy test within 14 days prior to initiating study treatment
- Ability to understand and willingness to sign the consent form
Who cannot join
- Other anti-cancer therapy administered between the time of tumor response to PD-1 or PD-L1 therapy and time of study enrollment Note: Patients treated with a combination of PD-1 or PD-L1 inhibiting therapy and other immunotherapy are eligible; patients taking hormonal anti-cancer therapies or steroids for central nervous system (CNS) edema management that, in the opinion of the investigator, are appropriate to continue are eligible.
- Any prior PD-1/PD-L1 therapy-related AE that, in the opinion of the investigator, warrants exclusion from participation in this trial
- Administration of any investigational agent within 4 weeks prior to initiating study treatment
- Known active hepatitis B or C
- Pregnancy or breastfeeding
- Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
About this study
Official title: Phase 2 Clinical Trial of Stereotactic Radiotherapy (SRT) and PD-1 or PD-L1 Inhibiting Therapy for Treatment of Advanced Solid Tumors After Disease Control on PD-1 or PD-L1 Inhibiting Therapy
The purpose of this study is to find out if having radiation therapy and continuing immunotherapy can improve the benefit of immunotherapy. There have been reports of patients who were treated with radiation therapy that not only caused the treated tumors to shrink or stop growing, but also resulted in tumors that had not been treated in other parts of the body to shrink or stop growing. This effect is thought to be brought about by cells in the body's immune system that become active as a result of the effects of radiation therapy. If radiation therapy can stimulate the immune system, it may be possible for immunotherapy to be helpful again in treating a cancer that the immunotherapy drug helped treat before. This study will also check if receiving immunotherapy at the end of radiation therapy has any effect on the side effects of radiation therapy or immunotherapy.
Read the detailed description
Stereotactic radiotherapy (SRT) will be delivered in up to 10 treatment fractions over 1 to 2 weeks. Patients will continue to receive the same FDA-approved programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor that they had been receiving at the time of disease progression through 52 weeks following completion of SRT.
Correlative blood samples will be collected at baseline, prior to the second SRT fraction, after the last SRT fraction (on the same day), and at 8, 24, and 52 weeks after the last SRT fraction. These samples will be used to determine the mechanistic immunologic effects of therapy.
- Conditions
- Solid Tumor
- Being tested
- Stereotactic radiotherapy, Biological: humanized anti-PD-1 monoclonal antibody, Biological: humanized anti-PD-L1 monoclonal antibody
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic radiotherapyRadiation
Also called SRT
Treatment will be planned to deliver a total of 18 to 60 Gy to the planning target volume (PTV) in 3 to 5 fractions over 1 to 2 weeks.
Biological: humanized anti-PD-1 monoclonal antibodyOther
Also called PD-1
Standard of Care - patient will continue to be given the same PD-1 inhibitor they were receiving prior to study registration
Biological: humanized anti-PD-L1 monoclonal antibodyOther
Also called PD-L1
Standard of Care - patient will continue to be given the same PD-L1 inhibitor they were receiving prior to study registration
| Study group | Role | What they receive |
|---|---|---|
| A: SBRT (body) irradiation only | Experimental | Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations Receives: Radiation: Stereotactic radiotherapy; Other: Biological: humanized anti-PD-1 monoclonal antibody; Other: Biological: humanized anti-PD-L1 monoclonal antibody |
| B: Patients receiving SBRT and SRS (body and brain) irradiation | Experimental | Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations Receives: Radiation: Stereotactic radiotherapy; Other: Biological: humanized anti-PD-1 monoclonal antibody; Other: Biological: humanized anti-PD-L1 monoclonal antibody |
| C: Patients receiving SRS (brain) irradiation only | Experimental | Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations Receives: Radiation: Stereotactic radiotherapy; Other: Biological: humanized anti-PD-1 monoclonal antibody; Other: Biological: humanized anti-PD-L1 monoclonal antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Improved Disease Control
- Number of patients with improved disease control at 24 weeks following RT [Time Frame: up to 24 weeks following RT] 1a. Number of participants with improved disease control (SD, PR or CR) at 24 weeks per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) 1b. For participants enrolled with brain metastases: number of participants with improved disease (SD, PR or CR) control at 24 weeks per per Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM)
Measured: Up to 24 weeks following SRT
Secondary outcomes (7)
Number of Patients Alive and Free From Progression at 24 Weeks Following SRT Per Unidimensional Immune-related Response Criteria (irRC)
Number of participants alive and without progression (irSD+irPR+irCR) at 24 weeks post-RT per unidimensional immune-related response criteria (irRC)
1b. For participants enrolled with brain metastases: number of participants alive and without progression (SD+PR+CR) at 24 weeks post-RT per immune Response Assessment in Neuro-Oncology (iRANO)
Measured: Up to 24 weeks following SRT
Number of Participants With Treatment Response in Irradiated Tumor Sites
Number of participants with treatment response in irradiated tumor sites at 24 weeks post-RT.
Measured: Up to 24 weeks following SRT
Number of Participants With Treatment Response in Non-irradiated Tumor Sites
Number of participants with treatment response in non-irradiated tumor sites at 24 weeks post-RT
Measured: Up to 24 weeks post-RT
Number of Patients Alive
Number of patients who are alive at 2 years after completion of SRT
Measured: 2 years following SRT
Number of Participants With Grade 3 or Greater Toxicity
Number of participants with grade 3 or greater toxicity from the regimen through 8 weeks following RT
Measured: Through 8 weeks following SRT
Number of Participants With Immune-related Toxicity From the Regimen
Number participants with immune-related AEs (irAEs) that require both checkpoint-inhibitor discontinuation and initiation of steroids reported per CTCAE v5.0
Measured: Up to 2 years following RT
Radiobiological Signatures Associated With the Regimen
Number participants with samples collected and number of participants with samples analyzed for immunologic effects of the regimen
Measured: Up to 52 weeks post SRT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2017
- Study start10 Oct 2017
- Primary completion27 Jan 2020
- Study completion22 Sep 2021
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 Solid TumorStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe 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
- Parallel groups
- Model description
- Steriotactic Radiotherapy followed by a commercially available PD-1 or PD-L1 inhibitor drug
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Alfredo Urdaneta, M.D., Principal investigator, Massey Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03220854
- Sponsor's protocol ID
- MCC-16-12436
- Other IDs
- P30CA016059
- Status last verified
- Dec 2021
- First submitted
- 14 Jul 2017
- Last updated
- 10 Jan 2022
- 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 10 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Clinical Trial of Stereotactic Radiotherapy (SRT) and PD-1 or PD-L1 Inhibiting Therapy for Treatment of Advanced Solid Tumors After Disease Control on PD-1 or PD-L1 Inhibiting Therapy
- ClinicalTrials.gov ID
- NCT03220854
- Acronym / sponsor ID
- MCC-16-12436
- Conditions
- Solid Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 10 Oct 2017 (actual)
- Primary completion
- 27 Jan 2020 (actual)
- Study completion
- 22 Sep 2021 (actual)
- First posted
- 18 Jul 2017 (actual)
- Results
- Posted 15 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out if having radiation therapy and continuing immunotherapy can improve the benefit of immunotherapy. There have been reports of patients who were treated with radiation therapy that not only caused the treated tumors to shrink or stop growing, but also resulted in tumors that had not been treated in other parts of the body to shrink or stop growing. This effect is thought to be brought about by cells in the body's immune system that become active as a result of the effects of radiation therapy. If radiation therapy can stimulate the immune system, it may be possible for immunotherapy to be helpful again in treating a cancer that the immunotherapy drug helped treat before. This study will also check if receiving immunotherapy at the end of radiation therapy has any effect on the side effects of radiation therapy or immunotherapy.
Detailed description
Stereotactic radiotherapy (SRT) will be delivered in up to 10 treatment fractions over 1 to 2 weeks. Patients will continue to receive the same FDA-approved programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor that they had been receiving at the time of disease progression through 52 weeks following completion of SRT.
Correlative blood samples will be collected at baseline, prior to the second SRT fraction, after the last SRT fraction (on the same day), and at 8, 24, and 52 weeks after the last SRT fraction. These samples will be used to determine the mechanistic immunologic effects of therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Steriotactic Radiotherapy followed by a commercially available PD-1 or PD-L1 inhibitor drug
| Arm | Type | Receives |
|---|---|---|
| A: SBRT (body) irradiation only | Experimental | Radiation: Stereotactic radiotherapy, Other: Biological: humanized anti-PD-1 monoclonal antibody, Other: Biological: humanized anti-PD-L1 monoclonal antibodyPatients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations |
| B: Patients receiving SBRT and SRS (body and brain) irradiation | Experimental | Radiation: Stereotactic radiotherapy, Other: Biological: humanized anti-PD-1 monoclonal antibody, Other: Biological: humanized anti-PD-L1 monoclonal antibodyPatients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations |
| C: Patients receiving SRS (brain) irradiation only | Experimental | Radiation: Stereotactic radiotherapy, Other: Biological: humanized anti-PD-1 monoclonal antibody, Other: Biological: humanized anti-PD-L1 monoclonal antibodyPatients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Pathologically-proven diagnosis of a solid tumor malignancy
- One of the following criteria must be met:
- Clinical or radiographic evidence of disease control (defined as best response of stable disease (SD) or partial response (PR) or combination of both for ≥ 16 weeks) without evidence of complete response (CR) or progression OR
- Clinical or radiographic evidence of disease progression during treatment with PD-1 or PD-L1 inhibiting therapy, following previous tumor response (CR, PR, or SD for ≥ 16 weeks) to PD-1 or PD-L1 inhibiting therapy, and, for patients who discontinued PD-1 or PD-L1 inhibiting therapy during response to therapy, disease progression must have occurred following at least 8 weeks of re-treatment with PD-1 or PD-L1 inhibiting therapy Note: Both the treating medical oncologist and radiation oncologist must be in agreement with determination of disease progression.
- Administration of a PD-1 or PD-L1 inhibitor within 60 days prior to study registration
Key exclusion criteria (6 listed)
- Other anti-cancer therapy administered between the time of tumor response to PD-1 or PD-L1 therapy and time of study enrollment Note: Patients treated with a combination of PD-1 or PD-L1 inhibiting therapy and other immunotherapy are eligible; patients taking hormonal anti-cancer therapies or steroids for central nervous system (CNS) edema management that, in the opinion of the investigator, are appropriate to continue are eligible.
- Any prior PD-1/PD-L1 therapy-related AE that, in the opinion of the investigator, warrants exclusion from participation in this trial
- Administration of any investigational agent within 4 weeks prior to initiating study treatment
- Known active hepatitis B or C
- Pregnancy or breastfeeding
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 |
|---|---|---|
| Stereotactic radiotherapyAlso: SRTTreatment will be planned to deliver a total of 18 to 60 Gy to the planning target volume (PTV) in 3 to 5 fractions over 1 to 2 weeks. | Radiation | A: SBRT (body) irradiation only, B: Patients receiving SBRT and SRS (body and brain) irradiation, C: Patients receiving SRS (brain) irradiation only |
| Biological: humanized anti-PD-1 monoclonal antibodyAlso: PD-1Standard of Care - patient will continue to be given the same PD-1 inhibitor they were receiving prior to study registration | Other | A: SBRT (body) irradiation only, B: Patients receiving SBRT and SRS (body and brain) irradiation, C: Patients receiving SRS (brain) irradiation only |
| Biological: humanized anti-PD-L1 monoclonal antibodyAlso: PD-L1Standard of Care - patient will continue to be given the same PD-L1 inhibitor they were receiving prior to study registration | Other | A: SBRT (body) irradiation only, B: Patients receiving SBRT and SRS (body and brain) irradiation, C: Patients receiving SRS (brain) irradiation only |
Primary outcome
Number of Patients With Improved Disease Control
Time frame: Up to 24 weeks following SRT
1. Number of patients with improved disease control at 24 weeks following RT [Time Frame: up to 24 weeks following RT] 1a. Number of participants with improved disease control (SD, PR or CR) at 24 weeks per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) 1b. For participants enrolled with brain metastases: number of participants with improved disease (SD, PR or CR) control at 24 weeks per per Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM)
7 secondary outcomes
Number of Patients Alive and Free From Progression at 24 Weeks Following SRT Per Unidimensional Immune-related Response Criteria (irRC)
Time frame: Up to 24 weeks following SRT
Number of Participants With Treatment Response in Irradiated Tumor Sites
Time frame: Up to 24 weeks following SRT
Number of Participants With Treatment Response in Non-irradiated Tumor Sites
Time frame: Up to 24 weeks post-RT
Number of Patients Alive
Time frame: 2 years following SRT
Number of Participants With Grade 3 or Greater Toxicity
Time frame: Through 8 weeks following SRT
Number of Participants With Immune-related Toxicity From the Regimen
Time frame: Up to 2 years following RT
Radiobiological Signatures Associated With the Regimen
Time frame: Up to 52 weeks post SRT
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 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.
Alfredo Urdaneta, M.D. principal investigator
Massey Cancer Center
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 Stereotactic radiotherapy, Biological: humanized anti-PD-1 monoclonal antibody and Biological: humanized anti-PD-L1 monoclonal antibody in people with Solid Tumor, run by Virginia Commonwealth University 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 13 inclusion and 6 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 10 Jan 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 15 Jan 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 Patients With Improved Disease Control (time frame: Up to 24 weeks following SRT). 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 10 Jan 2022.