Metastatic Microsatellite Stable Colorectal CarcinomaPhase 2NCT05518032
Pembrolizumab and Autologous Dendritic Cells for the Treatment of Refractory Colorectal Cancer (CRC)
A Phase 2 study testing Biopsy, Pembrolizumab and Therapeutic Autologous Dendritic Cells in people with Metastatic Microsatellite Stable Colorectal Carcinoma and Recurrent Colorectal Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.
Trial summary
The phase II trial tests whether pembrolizumab and dendritic cell-based treatment works to shrink tumors in patients with colorectal cancer that does not respond to treatment (refractory). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Microsatellite Stable Colorectal Carcinoma, Recurrent Colorectal Carcinoma, Stage III Colorectal Cancer AJCC v8
- What is being tested?
- Biopsy, Pembrolizumab and Therapeutic Autologous Dendritic Cells
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2024to 1 Oct 2026
- 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
- Age >= 18 years of age
- Recurrent and/or metastatic unresectable microsatellite stable (MSS) colorectal cancer
- At least 2 target lesions present per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at least one of which is amenable to biopsy and injection
- Prior treatment with, contra-indication to, or refusal of a fluoropyrimidine, irinotecan, oxaliplatin and an anti-EGFR targeted therapy (if RAS wt), as well as avastin/bevacizumab
- PD-1/PD-L1/PD-L2 treatment naïve patients are eligible
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Show all 16Show fewer
- Platelet >= 75,000/uL
- Hemoglobin >= 8 g/dL (without transfusion in the past 14 days)
- Absolute neutrophil count (ANC) >= 1500/uL
- Estimated creatinine clearance (Cockcroft Gault) >= 30 mL/min/ for participant with creatinine levels > 1.5 x institutional upper limit of normal (ULN)
- Total bilirubin: =< 2 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 2 x ULN
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) =< 3 x institutional ULN (=< 5 x ULN for participants with liver metastases)
- Women of childbearing potential must agree to use acceptable birth control methods for the duration of the study and until persistence of the study drug is no longer detected in the peripheral blood: This may be a period of several years. Methods for acceptable birth control include condoms, diaphragm or cervical cap with spermicide, intrauterine device, and hormonal contraception; it is recommended that a combination of two methods be used
- NOTE: If the risk of conception exists, patients must continue to use highly effective contraception for at least two years following the last study treatment administration
- A male participant must agree to use a contraception during the treatment period and for at least 1 year after the last dose of study treatment and refrain from donating sperm during this period
- Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Who cannot join
- Patients currently treated with systemic immunosuppressive agents. If a patient is currently on steroids, they must be on a steroid dose less than or equal to an equivalent prednisone dose of 10 mg daily
- Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- Has received prior chemotherapy or radiotherapy within 2 weeks of start of study intervention. All chemotherapy or radiation-related toxicities must be resolved to =< grade 1, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-CNS disease
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
Show all 16Show fewer
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
- Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection. Note: No HIV testing is required
- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected) infection. Note: no testing for hepatitis B and hepatitis C is required
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or nursing female participants
- Unwilling or unable to follow protocol requirements
- Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
Trial locations and contacts
1 site in 1 country.
United States1 site
Roswell Park Cancer Institute
Buffalo, New York, 14263
About this study
Official title: A Phase 2 Study of Intravenous Pembrolizumab and Intratumorally Injected Autologous Dendritic Cells (DCs) in Refractory Colorectal Cancer (CRC)
The phase II trial tests whether pembrolizumab and dendritic cell-based treatment works to shrink tumors in patients with colorectal cancer that does not respond to treatment (refractory). Pembrolizumab, also referred to as an immune checkpoint inhibitor drug, works by targeting molecules that act as a check and balance system for immune responses. Immune checkpoint inhibitor drugs are designed to either "unleash" or "enhance" the cancer immune responses that already exist by either (1) blocking inhibitory molecules or by (2) activating stimulatory molecules. Dendritic cell-based treatment works by boosting the immune system (a system in our bodies that protects us against infection) to recognize and destroy the cancer cells. This investigational treatment targets cancer cells and is made from the patient's own blood cells. Giving pembrolizumab and dendritic cell-based treatment may help shrink tumors in patients with colorectal cancer.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the clinical efficacy of pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs) in refractory metastatic colorectal cancer (CRC).
SECONDARY OBJECTIVES:
- To evaluate the safety profile of pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs) in CRC patients.
II. To assess progression-free survival (PFS) in CRC patients receiving pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs).
III. To assess overall survival (OS) in CRC patients receiving pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs).
IV. To assess objective response as determined by Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).
EXPLORATORY OBJECTIVES:
- To conduct correlative science studies including:
Ia. Comparison of the metastatic tissue specimen with regard to total numbers of infiltrating T cells, their CD4/CD8 ratios, frequencies of Tregs, and their expression of chemokine receptors.
Ib. Evaluate the local expression of T eff-attracting chemokines and T reg-favoring chemokines using immunofluorescence (IF) and reverse transcription-polymerase chain reaction (RT-PCR).
OUTLINE:
Patients receive pembrolizumab intravenously (IV) on days 8, 29, 50, and 71, and autologous dendritic cells intratumorally on days 1 and 8 in the absence of disease progression or unacceptable toxicity. Patients may also receive an autologous dendritic cells intratumorally on day 50.
After completion study treatment, patients are followed up at 30 and 90 days, and then every 3 months for 12 months.
- Conditions
- Metastatic Microsatellite Stable Colorectal Carcinoma, Recurrent Colorectal Carcinoma, Stage III Colorectal Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Unresectable Colorectal Carcinoma
- Being tested
- Biopsy, Pembrolizumab, Therapeutic Autologous Dendritic Cells
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiopsyProcedure or surgery
Also called BIOPSY_TYPE, Bx
Undergo biopsy
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
Therapeutic Autologous Dendritic CellsBiological
Given intratumorally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pembrolizumab, autologous dendritic cells) | Experimental | Patients receive pembrolizumab IV on days 8, 29, 50, and 71, and autologous dendritic cells intratumorally on days 1 and 8 in the absence of disease progression or unacceptable toxicity. Patients may also receive an autologous dendritic cells intratumorally on day 50. Receives: Procedure: Biopsy; Biological: Pembrolizumab; Biological: Therapeutic Autologous Dendritic Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate
Determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be estimated using a 90% confidence interval obtained by Jeffrey's prior method.
Measured: At 12 weeks
Secondary outcomes (4)
Incidence of toxicities and adverse events
Assessed as per Common Terminology Criteria for Adverse Events version 5.0 and tabulated by type and grade.
Measured: Up to 90 days after last dose
Progression-free survival
Will be summarized using standard Kaplan-Meier methods, where estimates of median survival will be obtained with 90% confidence intervals.
Measured: From initiation of study treatment regimen to disease progression or death from any cause, assessed up to 1 year
Overall survival
Will be summarized using standard Kaplan-Meier methods, where estimates of median survival will be obtained with 90% confidence intervals.
Measured: From the time of treatment initiation until death from any cause, assessed up to 1 year
Objective response rate
Determined by Immune-related RECIST. Will be estimated using a 90% confidence interval obtained by Jeffrey's prior method.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2022
- Study start1 Oct 2024 (estimated)
- Primary completion1 Oct 2026 (estimated)
- Study completion1 Oct 2026 (estimated)
Why it stopped: prioritization of studies
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Microsatellite Stable Colorectal CarcinomaStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sarbajit Mukherjee, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05518032
- Sponsor's protocol ID
- I - 1670021
- Other IDs
- NCI-2022-04955, I - 1670021
- Status last verified
- Sep 2024
- First submitted
- 24 Aug 2022
- Last updated
- 26 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Intravenous Pembrolizumab and Intratumorally Injected Autologous Dendritic Cells (DCs) in Refractory Colorectal Cancer (CRC)
- ClinicalTrials.gov ID
- NCT05518032
- Acronym / sponsor ID
- I - 1670021
- Conditions
- Metastatic Microsatellite Stable Colorectal Carcinoma, Recurrent Colorectal Carcinoma, Stage III Colorectal Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Unresectable Colorectal Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: prioritization of studies
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Study start
- 1 Oct 2024 (estimated)
- Primary completion
- 1 Oct 2026 (estimated)
- Study completion
- 1 Oct 2026 (estimated)
- First posted
- 26 Aug 2022 (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.
The phase II trial tests whether pembrolizumab and dendritic cell-based treatment works to shrink tumors in patients with colorectal cancer that does not respond to treatment (refractory). Pembrolizumab, also referred to as an immune checkpoint inhibitor drug, works by targeting molecules that act as a check and balance system for immune responses. Immune checkpoint inhibitor drugs are designed to either "unleash" or "enhance" the cancer immune responses that already exist by either (1) blocking inhibitory molecules or by (2) activating stimulatory molecules. Dendritic cell-based treatment works by boosting the immune system (a system in our bodies that protects us against infection) to recognize and destroy the cancer cells. This investigational treatment targets cancer cells and is made from the patient's own blood cells. Giving pembrolizumab and dendritic cell-based treatment may help shrink tumors in patients with colorectal cancer.
Detailed description
PRIMARY OBJECTIVE:
- To determine the clinical efficacy of pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs) in refractory metastatic colorectal cancer (CRC).
SECONDARY OBJECTIVES:
- To evaluate the safety profile of pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs) in CRC patients.
II. To assess progression-free survival (PFS) in CRC patients receiving pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs).
III. To assess overall survival (OS) in CRC patients receiving pembrolizumab in combination with intratumorally injected autologous dendritic cells (DCs).
IV. To assess objective response as determined by Immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).
EXPLORATORY OBJECTIVES:
- To conduct correlative science studies including:
Ia. Comparison of the metastatic tissue specimen with regard to total numbers of infiltrating T cells, their CD4/CD8 ratios, frequencies of Tregs, and their expression of chemokine receptors.
Ib. Evaluate the local expression of T eff-attracting chemokines and T reg-favoring chemokines using immunofluorescence (IF) and reverse transcription-polymerase chain reaction (RT-PCR).
OUTLINE:
Patients receive pembrolizumab intravenously (IV) on days 8, 29, 50, and 71, and autologous dendritic cells intratumorally on days 1 and 8 in the absence of disease progression or unacceptable toxicity. Patients may also receive an autologous dendritic cells intratumorally on day 50.
After completion study treatment, patients are followed up at 30 and 90 days, and then every 3 months for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pembrolizumab, autologous dendritic cells) | Experimental | Procedure: Biopsy, Biological: Pembrolizumab, Biological: Therapeutic Autologous Dendritic CellsPatients receive pembrolizumab IV on days 8, 29, 50, and 71, and autologous dendritic cells intratumorally on days 1 and 8 in the absence of disease progression or unacceptable toxicity. Patients may also receive an autologous dendritic cells intratumorally on day 50. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age >= 18 years of age
- Recurrent and/or metastatic unresectable microsatellite stable (MSS) colorectal cancer
- At least 2 target lesions present per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at least one of which is amenable to biopsy and injection
- Prior treatment with, contra-indication to, or refusal of a fluoropyrimidine, irinotecan, oxaliplatin and an anti-EGFR targeted therapy (if RAS wt), as well as avastin/bevacizumab
- PD-1/PD-L1/PD-L2 treatment naïve patients are eligible
Key exclusion criteria (16 listed)
- Patients currently treated with systemic immunosuppressive agents. If a patient is currently on steroids, they must be on a steroid dose less than or equal to an equivalent prednisone dose of 10 mg daily
- Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
- Has received prior chemotherapy or radiotherapy within 2 weeks of start of study intervention. All chemotherapy or radiation-related toxicities must be resolved to =< grade 1, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 2 weeks of radiotherapy) to non-CNS disease
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 |
|---|---|---|
| BiopsyAlso: BIOPSY_TYPE, BxUndergo biopsy | Procedure or surgery | Treatment (pembrolizumab, autologous dendritic cells) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Treatment (pembrolizumab, autologous dendritic cells) |
| Therapeutic Autologous Dendritic CellsGiven intratumorally | Biological | Treatment (pembrolizumab, autologous dendritic cells) |
Primary outcome
Objective response rate
Time frame: At 12 weeks
Determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be estimated using a 90% confidence interval obtained by Jeffrey's prior method.
4 secondary outcomes
Incidence of toxicities and adverse events
Time frame: Up to 90 days after last dose
Progression-free survival
Time frame: From initiation of study treatment regimen to disease progression or death from any cause, assessed up to 1 year
Overall survival
Time frame: From the time of treatment initiation until death from any cause, assessed up to 1 year
Objective response rate
Time frame: Up to 1 year
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 26 Sep 2024.
Related trials for Metastatic Microsatellite Stable Colorectal Carcinoma
Not yet recruitingPhase 2
Tovecimig Plus FOLFIRI in Second Line Metastatic Colorectal Cancer
Colorectal Cancer, Metastatic Colorectal Cancer
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
RecruitingPhase 2
FOLFIRI and Bevacizumab With or Without Pelareorep for Second-Line Treatment of Metastatic RAS-Mutated, Microsatellite-Stable Colorectal Cancer
Ras-mutated Metastatic Colorectal Cancer, mCRC
Active, not recruitingPhase 2
CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer
Metastatic Mismatch Repair Proficient Colorectal Carcinoma, Refractory Mismatch Repair Proficient Colorectal Carcinoma
RecruitingPhase 1
Phase 1 Study Of SAR445877 In Combination With FOLFOX6 And Bevacizumab As First-Line Treatment For Microsatellite Stable Metastatic Colorectal Cancer
Phase 1, SAR445877
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.
Sarbajit Mukherjee principal investigator
Roswell Park Cancer Institute
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 Biopsy, Pembrolizumab and Therapeutic Autologous Dendritic Cells in people with Metastatic Microsatellite Stable Colorectal Carcinoma and Recurrent Colorectal Carcinoma, run by Roswell Park Cancer Institute 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 16 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 26 Sep 2024. 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?
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?
Objective response rate (time frame: At 12 weeks). 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 26 Sep 2024.