Ignite Creation Date:
2025-12-25 @ 2:08 AM
Ignite Modification Date:
2026-02-28 @ 3:53 AM
Study NCT ID:
NCT03072160
Status:
COMPLETED
Last Update Posted:
2021-02-11
First Post:
2017-03-03
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Pembrolizumab in Recurrent or Metastatic Medullary Thyroid Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase II Trial of Pembrolizumab in Recurrent or Metastatic Medullary Thyroid Cancer
Status:
COMPLETED
Status Verified Date:
2021-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
Medullary thyroid cancer (MTC) is a tumor of the thyroid gland. Surgery is the only current treatment to cure it. The drug pembrolizumab (MK-3475) is a new type of cancer therapy. It works by allowing the immune system to detect and kill tumor cells.
Objective:
To test how pembrolizumab affects people with MTC and if it can offer them clinical benefit.
Eligibility:
People ages 18 and older with MTC
Patients who have recurrent or metastatic MTC, for whom surgery is not a curative option
Patients with some imaging evidence of MTC
Patients with minimal symptoms related to MTC
Design:
Participants will be screened with:
* Medical history
* Physical exam
* Blood, urine, and heart tests
* Computed tomography (CT) scan or magnetic resonance imaging (MRI): They lie in a machine that takes pictures of the body.
* Bone scan
Participants will be put in a group based on their treatment history:
* Group 1 if they have had an immune stimulating cancer vaccine
* Group 2 if they have had no vaccine
Participants will receive the study drug as a 30-minute intravenous (IV) infusion every 3 weeks. Treatment will continue for up to 2 years as long as they tolerate it and their disease does not get worse.
Participants will have physical exams and blood tests on the day of each infusion. They will have CT and bone scans every 3 months.
Participants may save biopsies before treatment and after starting treatment.
Participants will have a final visit 3-4 weeks after stopping treatment. This will include a physical exam and blood and heart tests.
After this study, participants can join a long-term follow-up study.
Medullary thyroid cancer (MTC) is a tumor of the thyroid gland. Surgery is the only current treatment to cure it. The drug pembrolizumab (MK-3475) is a new type of cancer therapy. It works by allowing the immune system to detect and kill tumor cells.
Objective:
To test how pembrolizumab affects people with MTC and if it can offer them clinical benefit.
Eligibility:
People ages 18 and older with MTC
Patients who have recurrent or metastatic MTC, for whom surgery is not a curative option
Patients with some imaging evidence of MTC
Patients with minimal symptoms related to MTC
Design:
Participants will be screened with:
* Medical history
* Physical exam
* Blood, urine, and heart tests
* Computed tomography (CT) scan or magnetic resonance imaging (MRI): They lie in a machine that takes pictures of the body.
* Bone scan
Participants will be put in a group based on their treatment history:
* Group 1 if they have had an immune stimulating cancer vaccine
* Group 2 if they have had no vaccine
Participants will receive the study drug as a 30-minute intravenous (IV) infusion every 3 weeks. Treatment will continue for up to 2 years as long as they tolerate it and their disease does not get worse.
Participants will have physical exams and blood tests on the day of each infusion. They will have CT and bone scans every 3 months.
Participants may save biopsies before treatment and after starting treatment.
Participants will have a final visit 3-4 weeks after stopping treatment. This will include a physical exam and blood and heart tests.
After this study, participants can join a long-term follow-up study.
Detailed Description:
Background:
* Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PDL1) therapies have had clinical success in a minority of unselected patients across multiple tumor types
* While many questions remain about optimal PD1/PDL1 staining techniques to pre-select responders, less focus is being place on how to optimize responses in a broader cohort of patients
* Emerging preclinical and clinical data supports the hypothesis that a strong immunologic response in the tumor microenvironment induces PDL1 expression on the tumor and is associated with better clinical response to anti-PD1/PDL1 therapies
* Therapeutic cancer vaccines are one strategy to induce an immunologic response to the tumor, thereby enhancing PDL1 expression and optimizing clinical responses across all patients
* Limited clinical data exists about the potential benefit of sequential therapy with a therapeutic cancer vaccine followed by PD1/PDL1 inhibition
* This study will explore the role of PD1 inhibition in medullary thyroid cancer and evaluate the potential differences based on previous vaccine therapy
Objective:
-The primary objective of this trial is to determine whether administering a PD1 inhibitor to patients with medullary thyroid cancer will permit a modest fraction to be able to experience a 50% or greater decline in calcitonin levels or experience a partial/complete response on imaging
Key Eligibility:
* Patients greater than or equal to 18 years of age with evidence of metastatic medullary thyroid cancer including disease that is evaluable on bone, computed tomography (CT) scan or magnetic resonance imaging (MRI)
* Must have elevated calcitonin levels greater than 40 pg/mL
* Patients with minimal or no disease related-symptoms (minimal symptoms will include those that do not affect activities of daily living or pain that does not require regularly schedule narcotics)
* Eastern Cooperative Oncology Group (ECOG) 0-1
* Should have no autoimmune diseases; no evidence of being immunocompromised; no serious inter-current medical illness
* No brain metastasis, history of seizures, encephalitis, or multiple sclerosis
Design:
* This is a phase II, open label, single center clinical trial where all patients receive the anti-PD1/PDL1 therapy pembrolizumab
* Patients will enroll in one of two cohorts: patients with previous vaccine therapy or patients without previous vaccine therapy
* All patients will be TKI naive with minimal symptoms (consistent with the eligibility for our current study)
* Based on our calcitonin findings with our current study of 30 patients, we have determined that a confirmed calcitonin decline of 50% would be a rare finding, providing compelling preliminary evidence of clinical activity
* A total of 30 patients will be enrolled in the proposed study (15 patients in each cohort). Given that we already have 30 patients on a study with vaccine, we would only need to identify and recruit 15 patients for the vaccine-naive cohort.
* Based on these metrics, we could have \>6 months of calcitonin data in 30 patients within 2 years from trial initiation
* Additional immune correlative capitalizing on the extensive immune monitoring experience of the Laboratory of Tumor Immunology and Biology (LTIB) will allow for assessments of antigen specific T-cells and 123 immune subsets. These findings could provide the basis for biomarker development when taken together with biochemical and clinical responses seen in this study
* Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PDL1) therapies have had clinical success in a minority of unselected patients across multiple tumor types
* While many questions remain about optimal PD1/PDL1 staining techniques to pre-select responders, less focus is being place on how to optimize responses in a broader cohort of patients
* Emerging preclinical and clinical data supports the hypothesis that a strong immunologic response in the tumor microenvironment induces PDL1 expression on the tumor and is associated with better clinical response to anti-PD1/PDL1 therapies
* Therapeutic cancer vaccines are one strategy to induce an immunologic response to the tumor, thereby enhancing PDL1 expression and optimizing clinical responses across all patients
* Limited clinical data exists about the potential benefit of sequential therapy with a therapeutic cancer vaccine followed by PD1/PDL1 inhibition
* This study will explore the role of PD1 inhibition in medullary thyroid cancer and evaluate the potential differences based on previous vaccine therapy
Objective:
-The primary objective of this trial is to determine whether administering a PD1 inhibitor to patients with medullary thyroid cancer will permit a modest fraction to be able to experience a 50% or greater decline in calcitonin levels or experience a partial/complete response on imaging
Key Eligibility:
* Patients greater than or equal to 18 years of age with evidence of metastatic medullary thyroid cancer including disease that is evaluable on bone, computed tomography (CT) scan or magnetic resonance imaging (MRI)
* Must have elevated calcitonin levels greater than 40 pg/mL
* Patients with minimal or no disease related-symptoms (minimal symptoms will include those that do not affect activities of daily living or pain that does not require regularly schedule narcotics)
* Eastern Cooperative Oncology Group (ECOG) 0-1
* Should have no autoimmune diseases; no evidence of being immunocompromised; no serious inter-current medical illness
* No brain metastasis, history of seizures, encephalitis, or multiple sclerosis
Design:
* This is a phase II, open label, single center clinical trial where all patients receive the anti-PD1/PDL1 therapy pembrolizumab
* Patients will enroll in one of two cohorts: patients with previous vaccine therapy or patients without previous vaccine therapy
* All patients will be TKI naive with minimal symptoms (consistent with the eligibility for our current study)
* Based on our calcitonin findings with our current study of 30 patients, we have determined that a confirmed calcitonin decline of 50% would be a rare finding, providing compelling preliminary evidence of clinical activity
* A total of 30 patients will be enrolled in the proposed study (15 patients in each cohort). Given that we already have 30 patients on a study with vaccine, we would only need to identify and recruit 15 patients for the vaccine-naive cohort.
* Based on these metrics, we could have \>6 months of calcitonin data in 30 patients within 2 years from trial initiation
* Additional immune correlative capitalizing on the extensive immune monitoring experience of the Laboratory of Tumor Immunology and Biology (LTIB) will allow for assessments of antigen specific T-cells and 123 immune subsets. These findings could provide the basis for biomarker development when taken together with biochemical and clinical responses seen in this study
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 17-C-0061 | None | None | View |