Microsatellite Instability HighPhase 2NCT04001101
Anti-PD-1 +/- RT for MSI-H Solid Tumors
A Phase 2 study testing RT and Anti-PD-1 and Anti-PD-1 in people with Microsatellite Instability High and Mismatch Repair Deficiency, run by University of Colorado, Denver at 1 site in United States.
Trial summary
To determine if the out-of-field ORR is improved with the addition of radiation therapy to anti-PD-1 for patients with MSI-H/dMMR metastatic solid tumors. Determine the rates of in-field tumor control, disease control (stable disease, partial response, complete response), durability of disease response… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Microsatellite Instability High, Mismatch Repair Deficiency, Colorectal Cancer
- What is being tested?
- RT and Anti-PD-1 and Anti-PD-1
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2019to 17 Nov 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision to sign and date the consent form.
- Stated willingness to comply with all study procedures and be available for the duration of the study.
- Adult patients, 18-100 years of age.
- ECOG 0 or 1.
- Unresectable or metastatic MSI-H/dMMR tumors eligible to receive pembrolizumab according to FDA-approved indications:
- Solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options OR
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- Colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan11
- Confirmation from medical or gynecologic oncology that the patient is eligible to receive pembrolizumab per FDA-approved indication for patients not currently receiving pembrolizumab .
- At least one site of disease amenable to radiation therapy per the acceptable dosing regimens outlined in section 6.2, and at least one additional site of measurable disease suitable for out-of-field response assessment.
- Adequate baseline labs for initiation of trial treatment:
- absolute neutrophil count (ANC) >1,000/µL
- platelets >75,000/µL
- hemoglobin >8 g/dL
- serum creatinine < 1.5 x ULN
- serum total bilirubin < 1.5 x ULN
- AST and ALT < 2.5 x ULN, or < 5 x ULN if liver metastasis are present
Who cannot join
- Pregnant women. Pregnancy testing is required for all female subjects of childbearing potential.
- Patients with active collagen vascular disease (CVD), specifically systemic lupus erythematosus or scleroderma. Patients with a history of CVD without evidence of active disease are eligible for enrollment at the discretion of the study PI.
- History of immunodeficiency, hypersensitivity to pembrolizumab, or other medical contraindication to receipt of pembrolizumab.
- Active infection.
- Active CNS metastases. Patients with treated CNS metastases are eligible.
- Patients with a separate non-cutaneous cancer diagnosis for which the patient has not been without evidence of disease for at least 5 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Hospital
Denver, Colorado, 80045
About this study
Official title: A Randomized Phase II Study of Anti-PD-1 and Limited Metastatic Site Radiation Therapy Versus Anti-PD-1 Alone for Patients With Microsatellite Instability-high (MSI-H) and Mismatch Repair Deficient (dMMR) Metastatic Solid Tumors
To determine if the out-of-field ORR is improved with the addition of radiation therapy to anti-PD-1 for patients with MSI-H/dMMR metastatic solid tumors. Determine the rates of in-field tumor control, disease control (stable disease, partial response, complete response), durability of disease response, progression-free survival, overall survival, and to assess quality of life and toxicity. Determine the chronology and profile of the radiation-associated immune response.
Read the detailed description
This is a randomized phase II study with a primary objective to compare the objective response rate (ORR) for anti-PD-1 therapy alone versus anti-PD-1 therapy and limited metastatic site radiation, in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic solid tumors. The anti-PD-1 agent, pembrolizumab, received recent FDA accelerated approval for the use in patients with metastatic MSI-H or dMMR solid tumors that have progressed following prior treatment or without satisfactory alternative treatment options. FDA approval for pembrolizumab was based on the results of five multi-cohort, multi-center, single-arm trials, which together showed an ORR of 39.6% among 149 patients with MSI-H/dMMR cancers. Importantly, there is mounting preclinical and clinic evidence supporting the safety and efficacy of combining radiation therapy with systemic immunotherapy, although no prospective comparative data, to the best of our knowledge. In this study, the investigators will focus on patients with MSI-H/dMMR tumors, given their baseline responsiveness to immune checkpoint inhibition, and test the hypothesis that ORR will be improved with radiation and anti-PD-1 therapy compared to anti-PD-1 therapy alone, through a randomized phase II trial design.
- Being tested
- RT and Anti-PD-1, Anti-PD-1
- Keywords
- Solid tumor, Colorectal cancer, Unresectable or metastatic
- Medical subject headings
- Turcot syndrome, Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RT and Anti-PD-1Combination product
limited metastatic site radiation
Anti-PD-1Drug
anti-PD-1 therapy alone
| Study group | Role | What they receive |
|---|---|---|
| RT and Anti-PD-1 | Active comparator | In the pembrolizumab + RT arm, pembrolizumab will be started on study within 7 days (+/- 7 days) of start of RT.
Pembrolizumab will be given as standard of care in both arms Receives: Combination Product: RT and Anti-PD-1 |
| Anti-PD-1 | Placebo comparator | anti-PD-1 therapy alone Pembrolizumab will be given as standard of care in both arms Receives: Drug: Anti-PD-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Out-of-field ORR improvement
- Out-of-field objective response rate (ORR: CR+PR) according to RECIST 1.1 assessment
Measured: 12 months
Secondary outcomes (6)
in-field tumor control and disease control
In-field tumor control and disease control will be defined as SD, PR, or CR, of the target lesion, by RECIST 1.1 criteria
Measured: 12 Months
Determine the chronology and profile of the radiation-associated immune response.
The University of Colorado School of Medicine Human Immune Monitoring Shared Resource (HIMSR) will quantify peripheral CD8, CD4, and regulatory T cell populations and characterize the relative functional state of these cells using activation markers (CD45RO, ICOS, and CD25) and inhibitory markers (TIM-3, CTLA-4, LAG-3, and PD-1). The HIMSR will also characterize peripheral dendritic cells (pDCs, CD1c+, and CD141+ subsets), monocytes (classical and non-classical subsets), myeloid-derived suppressor cells (MDSCs, granulocytic and monocytic subsets), and expression of activation (CD80 and HLA-DR) and inhibitory molecules (PDL1) on these cells. Further, cytokine production by NK cells, B cells, T cells, and monocytes will be measured by flow cytometry after brief ex-vivo stimulation. The HIMSR will also perform a protein multiplex array of 40 potential biomarkers in plasma.
Measured: 12 months
Durability of disease response
In patients that achieve an objective response to pembrolizumab +/- RT, durability of response will be measured from the initiation of pembrolizumab until PD.
Measured: 12 months
Progression-free Survival
Progression-free survival will be measured from the date of initiation of pembrolizumab to the time of tumor progression or death from any cause for one year.
Measured: 12 months
Overall Survival
Overall survival will be measured from the date of initiation of pembrolizumab to the time of death from any cause for one year.
Measured: 12 Months
Quality of life score
Quality of life questionnaire, 28 questions rating experience from 1 to 4 (4 being "very much", 1 being "not at all") and two questions rating overall health and quality of life on a scale from 1 to 7 (7 being excellent)
Measured: 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2019
- Study start10 Oct 2019
- Primary completion17 Nov 2021
- Study completion17 Nov 2021
Why it stopped: PI has decided to withdraw the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Microsatellite Instability HighStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Cancer League of Colorado
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04001101
- Sponsor's protocol ID
- 19-0556.cc
- Other IDs
- P30CA046934
- Status last verified
- Nov 2021
- First submitted
- 10 Jun 2019
- Last updated
- 30 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Anti-PD-1 and Limited Metastatic Site Radiation Therapy Versus Anti-PD-1 Alone for Patients With Microsatellite Instability-high (MSI-H) and Mismatch Repair Deficient (dMMR) Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT04001101
- Acronym / sponsor ID
- 19-0556.cc
- Keywords
- Solid tumor, Colorectal cancer, Unresectable or metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI has decided to withdraw the study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Cancer League of Colorado
- Study start
- 10 Oct 2019 (actual)
- Primary completion
- 17 Nov 2021 (actual)
- Study completion
- 17 Nov 2021 (actual)
- First posted
- 27 Jun 2019 (actual)
- 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.
To determine if the out-of-field ORR is improved with the addition of radiation therapy to anti-PD-1 for patients with MSI-H/dMMR metastatic solid tumors. Determine the rates of in-field tumor control, disease control (stable disease, partial response, complete response), durability of disease response, progression-free survival, overall survival, and to assess quality of life and toxicity. Determine the chronology and profile of the radiation-associated immune response.
Detailed description
This is a randomized phase II study with a primary objective to compare the objective response rate (ORR) for anti-PD-1 therapy alone versus anti-PD-1 therapy and limited metastatic site radiation, in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic solid tumors. The anti-PD-1 agent, pembrolizumab, received recent FDA accelerated approval for the use in patients with metastatic MSI-H or dMMR solid tumors that have progressed following prior treatment or without satisfactory alternative treatment options. FDA approval for pembrolizumab was based on the results of five multi-cohort, multi-center, single-arm trials, which together showed an ORR of 39.6% among 149 patients with MSI-H/dMMR cancers. Importantly, there is mounting preclinical and clinic evidence supporting the safety and efficacy of combining radiation therapy with systemic immunotherapy, although no prospective comparative data, to the best of our knowledge. In this study, the investigators will focus on patients with MSI-H/dMMR tumors, given their baseline responsiveness to immune checkpoint inhibition, and test the hypothesis that ORR will be improved with radiation and anti-PD-1 therapy compared to anti-PD-1 therapy alone, through a randomized phase II trial design.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RT and Anti-PD-1 | Active comparator | Combination Product: RT and Anti-PD-1In the pembrolizumab + RT arm, pembrolizumab will be started on study within 7 days (+/- 7 days) of start of RT. Pembrolizumab will be given as standard of care in both arms |
| Anti-PD-1 | Placebo comparator | Drug: Anti-PD-1anti-PD-1 therapy alone Pembrolizumab will be given as standard of care in both arms |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Provision to sign and date the consent form.
- Stated willingness to comply with all study procedures and be available for the duration of the study.
- Adult patients, 18-100 years of age.
- ECOG 0 or 1.
- Unresectable or metastatic MSI-H/dMMR tumors eligible to receive pembrolizumab according to FDA-approved indications:
Key exclusion criteria (6 listed)
- Pregnant women. Pregnancy testing is required for all female subjects of childbearing potential.
- Patients with active collagen vascular disease (CVD), specifically systemic lupus erythematosus or scleroderma. Patients with a history of CVD without evidence of active disease are eligible for enrollment at the discretion of the study PI.
- History of immunodeficiency, hypersensitivity to pembrolizumab, or other medical contraindication to receipt of pembrolizumab.
- Active infection.
- Active CNS metastases. Patients with treated CNS metastases are eligible.
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 |
|---|---|---|
| RT and Anti-PD-1limited metastatic site radiation | Combination product | RT and Anti-PD-1 |
| Anti-PD-1anti-PD-1 therapy alone | Drug | Anti-PD-1 |
Primary outcome
Out-of-field ORR improvement
Time frame: 12 months
• Out-of-field objective response rate (ORR: CR+PR) according to RECIST 1.1 assessment
6 secondary outcomes
in-field tumor control and disease control
Time frame: 12 Months
Determine the chronology and profile of the radiation-associated immune response.
Time frame: 12 months
Durability of disease response
Time frame: 12 months
Progression-free Survival
Time frame: 12 months
Overall Survival
Time frame: 12 Months
Quality of life score
Time frame: 12 Months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2021.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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 RT and Anti-PD-1 and Anti-PD-1 in people with Microsatellite Instability High and Mismatch Repair Deficiency, run by University of Colorado, Denver 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 16 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: withdrawn, as of the sponsor's last update on 30 Nov 2021. 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. Some participants in this study may receive a placebo. 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 was withdrawn before enrolling participants, so there are no results.
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?
Out-of-field ORR improvement (time frame: 12 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 30 Nov 2021.