Metastatic Colon CancerPhase 1/2NCT02834052
Pembrolizumab + Poly-ICLC in MRP Colon Cancer
A Phase 1/2 study testing pembrolizumab and Poly-ICLC in people with Metastatic Colon Cancer and Solid Tumor, run by Asha Nayak at 1 site in United States.
Trial summary
The main purpose of this study is to determine the dose of poly-ICLC that is safe and tolerable when it is combined with pembrolizumab in patients with colon cancer. This study will also evaluate how the combination of pembrolizumab and poly-ICLC activates the immune system in the patient's blood and inside the tumor… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colon Cancer, Solid Tumor
- What is being tested?
- pembrolizumab and Poly-ICLC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2018to 29 Jul 2022
- Phase
- Phase 1/2
- 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
- Be willing and able to provide written informed consent for the trial
- Have measurable disease based on RECIST 1.1 (Phase 2)
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion
- Have a performance status of 0 or 1 on the ECOG Performance Scale
- Have adequate organ function, according to screening labs performed within 10 days of treatment initiation
- Subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
Who cannot join
- Currently participating/previously participated in a therapeutic study and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- 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 a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
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- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has active autoimmune disease that has required systemic treatment in the past 2 years
Trial locations and contacts
1 site in 1 country.
United States1 site
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912
About this study
Official title: A Phase I/II Trial of Pembrolizumab (MK-3475) and Poly-ICLC in Patients With Metastatic Mismatch Repair-proficient (MRP) Colon Cancer
The main purpose of this study is to determine the dose of poly-ICLC that is safe and tolerable when it is combined with pembrolizumab in patients with colon cancer. This study will also evaluate how the combination of pembrolizumab and poly-ICLC activates the immune system in the patient's blood and inside the tumor; how it affects the size and number of tumor(s) in each patient; and how effective the combination is in patients with colon cancer that is unlikely to respond to pembrolizumab alone.
Read the detailed description
Mismatch repair genes normally serve to fix the small glitches that occur when DNA is copied as cells divide. In 1993, researchers discovered that mutations in human mismatch repair genes play a key role in the development of certain forms of colorectal cancer; individuals who are deficient in these mismatch repair genes are at high risk for colorectal cancer. Accumulating evidence has shown that immunotherapy may be most effective against these cancers.
Programmed cell death protein 1, also known as PD-1, functions as an immune checkpoint, down-regulating the immune system by preventing the activation of T-cells, which in turn reduces autoimmunity and promotes self-tolerance. A new class of immunotherapy drugs that block PD-1, the PD-1 inhibitors, activate the immune system to attack tumors and are therefore used with varying success to treat some types of cancer.
Current clinical trials are showing that patients whose tumors are mismatch repair deficient are more likely to respond to immune-boosting anti-PD-1 drugs-such as pembrolizumab-than those with tumors proficient in mismatch repair. The idea is that the greater the number of DNA glitches in a tumor cell, the more abnormal proteins it will produce-and the more abnormal proteins that are generated, the greater the odds that the body's immune cells will regard the tumor cells as "foreign" and target them for destruction. Thus far, PD-1 inhibitors have shown great promise for mismatch repair deficient cancer patients, but not for mismatch repair proficient (MRP) cancer patients.
In this clinical trial, the investigators hypothesize that treating MRP colon cancer patients with immunostimulating agent poly-ICLC will generate an inflammatory response, increasing epitope recognition and development of tumor reactive T-cells at the tumor site. However, interferon alpha and gamma produced by the poly-ICLC will increase PD-L1 expression and limit new T-cell development. Thus, PD1 blockade will increase the effectiveness of treatment with pembrolizumab.
- Conditions
- Metastatic Colon Cancer, Solid Tumor
- Being tested
- pembrolizumab, Poly-ICLC
- Keywords
- Immunotherapy, Anti-programmed death 1 (PD-1) inhibitor, Immunostimulant, monoclonal antibody, TLR3 agonist, Immunologic factors
- Medical subject headings
- Colonic Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pembrolizumabDrug
Also called MK-3475, Keytruda
200mg pembrolizumab will be given intravenously on Day 1 of each 3-week cycle
Poly-ICLCDrug
Also called polyinosinic-polycytidylic acid-polylysine-carboxymethylcellulose, Hiltonol
The maximum tolerated dose of Poly ICLC will be given twice weekly, in each 3-week cycle:
Week 1, Days 1 and 4
Week 2, Days 8 and 11
Week 3, Days 15 and 18
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 | Experimental | This "Run In" phase is aimed to determine if poly-ICLC can be safely combined with standard dosages of pembrolizumab:
i. Pembrolizumab will be administered 200 mg intravenously (IV) every 3 weeks (q3w)
ii. Poly-ICLC will be administered intramuscularly (IM) twice weekly at one of two dose levels: 1 mg or 2 mg
Each dose level will enroll 3-6 participants, up to 12 participants total, depending on the occurrence of dose limiting toxicities (DLT) at each dosing level.
Participants may receive treatment for 1 year (~17 cycles). Receives: Drug: pembrolizumab; Drug: Poly-ICLC |
| Phase 2 | Experimental | In Phase 2, all participants will receive the standard pembrolizumab dose (200 mg IV q3w) in addition to the maximum tolerated dose of poly-ICLC (either 1 mg or 2 mg), as determined by the Phase 1 arm.
Up to 30 participants will be treated in Phase 2. Participants may receive treatment for 1 year (~17 cycles). Receives: Drug: pembrolizumab; Drug: Poly-ICLC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Determine the Maximum Tolerated Dose of Poly-ICLC That Can be Combined With Pembrolizumab
A minimum of 3 participants will be treated at dose level 1 (1mg).
- If 0 out of 3 participants experience dose limiting toxicities (DLT), then dose escalation will proceed to dose level 2 (2mg).
- If 1 out of 3 participants experience DLT, a cohort of additional 3 participants will be assigned to the same dose level (1mg).
- If 2 or more participants of 3 (or 6) experience DLT at dose level 1, then enrollment of participants will be stopped.
Measured: 12 months
Phase 1 and 2: Determine the Response Rate of Metastatic MRP Colon Cancer (That Has Progressed Following Two Lines of Therapy in the Metastatic Setting) to the Combination of Pembrolizumab and Poly-ICLC
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: From baseline to disease progression (Expected 12-24 months)
Determine the Overall Survival Rate for Recurrent Metastatic MRP Colon Cancer Response to the Combination of Pembrolizumab and Poly-ICLC
The overall survival rate of response to the combination of pembrolizumab and poly-ICLC administered at the Recommended Phase 2 Dose (RP2D) will be estimated along with the correspondent 95% confidence interval.
Measured: From baseline to disease progression (up to 24 months)
Secondary outcomes (3)
Determine the Adverse Event Profile and Dose Limiting Toxicities of the Combination of Pembrolizumab and Poly-ICLC
The adverse event profile will be presented by dose level of the combination treatment for the phase I portion
Measured: 12 months
Determine the 20-week Progression Free Survival Rate of Recurrent Metastatic MRP Colon Cancer to the Combination of Pembrolizumab and Poly-ICLC
The 20-week progression free survival rate for the combination of pembrolizumab and poly-ICLC administered at the Recommended Phase 2 Dose (RP2D) will be estimated along with the correspondent 95% confidence interval.
Measured: 20 weeks
Determine the Duration of Response of Recurrent Metastatic MRP Colon Cancer to the Combination of Pembrolizumab and Poly-ICLC
The duration of response to the combination of pembrolizumab and poly-ICLC administered at the Recommended Phase 2 Dose (RP2D) will be estimated along with the correspondent 95% confidence interval.
Measured: From baseline to disease progression (up to 24 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2016 (estimated)
- Study start10 Jan 2018
- Primary completion29 Jul 2022
- Study completion29 Jul 2022
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 Metastatic Colon CancerStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asha Nayak
- Sponsor type
- University, hospital or other
- Collaborators
- Oncovir, Inc., Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Asha Nayak, Augusta University
- Investigators
- Asha Nayak, MD, Principal investigator, Georgia Cancer Center at Augusta UniversitySharad Ghamande, MD, Study director, Georgia Cancer Center at Augusta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02834052
- Sponsor's protocol ID
- GCC-16047
- Status last verified
- Jun 2024
- First submitted
- 15 Jun 2016
- Last updated
- 7 Jun 2024
- 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 7 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Pembrolizumab (MK-3475) and Poly-ICLC in Patients With Metastatic Mismatch Repair-proficient (MRP) Colon Cancer
- ClinicalTrials.gov ID
- NCT02834052
- Acronym / sponsor ID
- GCC-16047
- Conditions
- Metastatic Colon Cancer, Solid Tumor
- Keywords
- Immunotherapy, Anti-programmed death 1 (PD-1) inhibitor, Immunostimulant, monoclonal antibody, TLR3 agonist, Immunologic factors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Asha NayakUniversity, hospital or other
- Collaborators
- Oncovir, Inc., Merck Sharp & Dohme LLC
- Study start
- 10 Jan 2018 (actual)
- Primary completion
- 29 Jul 2022 (actual)
- Study completion
- 29 Jul 2022 (actual)
- First posted
- 15 Jul 2016 (estimated)
- Results
- Posted 7 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to determine the dose of poly-ICLC that is safe and tolerable when it is combined with pembrolizumab in patients with colon cancer. This study will also evaluate how the combination of pembrolizumab and poly-ICLC activates the immune system in the patient's blood and inside the tumor; how it affects the size and number of tumor(s) in each patient; and how effective the combination is in patients with colon cancer that is unlikely to respond to pembrolizumab alone.
Detailed description
Mismatch repair genes normally serve to fix the small glitches that occur when DNA is copied as cells divide. In 1993, researchers discovered that mutations in human mismatch repair genes play a key role in the development of certain forms of colorectal cancer; individuals who are deficient in these mismatch repair genes are at high risk for colorectal cancer. Accumulating evidence has shown that immunotherapy may be most effective against these cancers.
Programmed cell death protein 1, also known as PD-1, functions as an immune checkpoint, down-regulating the immune system by preventing the activation of T-cells, which in turn reduces autoimmunity and promotes self-tolerance. A new class of immunotherapy drugs that block PD-1, the PD-1 inhibitors, activate the immune system to attack tumors and are therefore used with varying success to treat some types of cancer.
Current clinical trials are showing that patients whose tumors are mismatch repair deficient are more likely to respond to immune-boosting anti-PD-1 drugs-such as pembrolizumab-than those with tumors proficient in mismatch repair. The idea is that the greater the number of DNA glitches in a tumor cell, the more abnormal proteins it will produce-and the more abnormal proteins that are generated, the greater the odds that the body's immune cells will regard the tumor cells as "foreign" and target them for destruction. Thus far, PD-1 inhibitors have shown great promise for mismatch repair deficient cancer patients, but not for mismatch repair proficient (MRP) cancer patients.
In this clinical trial, the investigators hypothesize that treating MRP colon cancer patients with immunostimulating agent poly-ICLC will generate an inflammatory response, increasing epitope recognition and development of tumor reactive T-cells at the tumor site. However, interferon alpha and gamma produced by the poly-ICLC will increase PD-L1 expression and limit new T-cell development. Thus, PD1 blockade will increase the effectiveness of treatment with pembrolizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 | Experimental | Drug: pembrolizumab, Drug: Poly-ICLCThis "Run In" phase is aimed to determine if poly-ICLC can be safely combined with standard dosages of pembrolizumab: i. Pembrolizumab will be administered 200 mg intravenously (IV) every 3 weeks (q3w) ii. Poly-ICLC will be administered intramuscularly (IM) twice weekly at one of two dose levels: 1 mg or 2 mg Each dose level will enroll 3-6 participants, up to 12 participants total, depending on the occurrence of dose limiting toxicities (DLT) at each dosing level. Participants may receive treatment for 1 year (~17 cycles). |
| Phase 2 | Experimental | Drug: pembrolizumab, Drug: Poly-ICLCIn Phase 2, all participants will receive the standard pembrolizumab dose (200 mg IV q3w) in addition to the maximum tolerated dose of poly-ICLC (either 1 mg or 2 mg), as determined by the Phase 1 arm. Up to 30 participants will be treated in Phase 2. Participants may receive treatment for 1 year (~17 cycles). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Be willing and able to provide written informed consent for the trial
- Have measurable disease based on RECIST 1.1 (Phase 2)
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion
- Have a performance status of 0 or 1 on the ECOG Performance Scale
- Have adequate organ function, according to screening labs performed within 10 days of treatment initiation
Key exclusion criteria (9 listed)
- Currently participating/previously participated in a therapeutic study and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- 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 a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
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: MK-3475, Keytruda200mg pembrolizumab will be given intravenously on Day 1 of each 3-week cycle | Drug | Phase 1, Phase 2 |
| Poly-ICLCAlso: polyinosinic-polycytidylic acid-polylysine-carboxymethylcellulose, HiltonolThe maximum tolerated dose of Poly ICLC will be given twice weekly, in each 3-week cycle: Week 1, Days 1 and 4 Week 2, Days 8 and 11 Week 3, Days 15 and 18 | Drug | Phase 1, Phase 2 |
Primary outcome
Phase 1: Determine the Maximum Tolerated Dose of Poly-ICLC That Can be Combined With Pembrolizumab
Time frame: 12 months
A minimum of 3 participants will be treated at dose level 1 (1mg). * If 0 out of 3 participants experience dose limiting toxicities (DLT), then dose escalation will proceed to dose level 2 (2mg). * If 1 out of 3 participants experience DLT, a cohort of additional 3 participants will be assigned to the same dose level (1mg). * If 2 or more participants of 3 (or 6) experience DLT at dose level 1, then enrollment of participants will be stopped.
Phase 1 and 2: Determine the Response Rate of Metastatic MRP Colon Cancer (That Has Progressed Following Two Lines of Therapy in the Metastatic Setting) to the Combination of Pembrolizumab and Poly-ICLC
Time frame: From baseline to disease progression (Expected 12-24 months)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Determine the Overall Survival Rate for Recurrent Metastatic MRP Colon Cancer Response to the Combination of Pembrolizumab and Poly-ICLC
Time frame: From baseline to disease progression (up to 24 months)
The overall survival rate of response to the combination of pembrolizumab and poly-ICLC administered at the Recommended Phase 2 Dose (RP2D) will be estimated along with the correspondent 95% confidence interval.
3 secondary outcomes
Determine the Adverse Event Profile and Dose Limiting Toxicities of the Combination of Pembrolizumab and Poly-ICLC
Time frame: 12 months
Determine the 20-week Progression Free Survival Rate of Recurrent Metastatic MRP Colon Cancer to the Combination of Pembrolizumab and Poly-ICLC
Time frame: 20 weeks
Determine the Duration of Response of Recurrent Metastatic MRP Colon Cancer to the Combination of Pembrolizumab and Poly-ICLC
Time frame: From baseline to disease progression (up to 24 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2024.
- 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.
Asha Nayak, MD principal investigator
Georgia Cancer Center at Augusta University
Sharad Ghamande, MD study director
Georgia Cancer Center at Augusta University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing pembrolizumab and Poly-ICLC in people with Metastatic Colon Cancer and Solid Tumor, run by Asha Nayak 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 6 inclusion and 9 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 7 Jun 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 7 Jun 2024). 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?
Phase 1: Determine the Maximum Tolerated Dose of Poly-ICLC That Can be Combined With Pembrolizumab (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2024.