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This study is a pilot study to evaluate high-dose conformal radiation therapy (HDCRT) administered in combination with pembrolizumab in patients with solid tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: HDCRT administered with first dose of pembrolizumab | Experimental | Pembrolizumab (200 mg) plus HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) are both administered beginning on day 1. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. |
|
| Arm B: HDCRT administered between doses 1& 2 of pembrolizumab | Experimental | Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 22. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 22. |
|
| Arm C: HDCRT administered prior to first dose of pembrolizumab | Experimental | Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 1. Pembrolizumab will be administered on days 22, 43, 64, and 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the four doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High-Dose Conformal Radiation Therapy | Radiation | 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety: Adverse Event Profile | Adverse events related to HDCRT with immunotherapy, delivered concurrently (Arm A) or sequentially (Arms B and C) | up to 24 months for adverse events; up to 27 months for serious adverse events |
| Enumeration of T Cells in Tumor Tissue | Log-normalized enumeration of CD8+ T cells and FoxP3+ cells in untreated and treated tumor tissue by immunohistochemical analysis to estimate group differences and changes over time in immune assay parameters in tumor. | At Baseline, Day 22 of treatment, and Day 43 or treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Enumeration of Circulating Immune Cells | Enumeration of CD8+ and CD4+ T cells in untreated and treated blood samples to estimate group differences and changes over time in immune assay parameters in PBMC | at Baseline and at Days 22 , 43, 64, and 85 of treatment |
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Inclusion Criteria:
Subjects must have a histologically or cytologically proven advanced solid tumor malignancy for which palliative radiation is recommended. In solid tumors where pembrolizumab has been approved for use, patients may receive pembrolizumab as indicated, in the context of this protocol. In solid tumors where pembrolizumab has not been approved for use, the following criteria apply:
Palliative radiation therapy may be recommended for primary tumor and/or any metastatic site that is accessible to biopsy.
At least one site of disease that is accessible to radiation and multiple biopsies. Subjects may have disease that is encompassed within the radiation field or may have known disease both inside and outside of the radiation field.
Must be able to provide tissue from 2-3 separate biopsy procedures that will be completed throughout the course of the study.
A performance status of 0, 1 or 2 on the ECOG Performance Scale.
Subjects must demonstrate adequate organ function.
A life expectancy ≥ 6 months.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| James Larner, MD | University of Virginia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Virginia | Charlottesville | Virginia | 22908 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: HDCRT Administered With First Dose of Pembrolizumab | Pembrolizumab (200 mg) plus HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) are both administered beginning on day 1. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| FG001 | Arm B: HDCRT Administered Between Doses 1& 2 of Pembrolizumab | Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 22. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 22. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| FG002 | Arm C: HDCRT Administered Prior to First Dose of Pembrolizumab | Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 1. Pembrolizumab will be administered on days 22, 43, 64, and 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the four doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: HDCRT Administered With First Dose of Pembrolizumab | Pembrolizumab (200 mg) plus HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) are both administered beginning on day 1. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety: Adverse Event Profile | Adverse events related to HDCRT with immunotherapy, delivered concurrently (Arm A) or sequentially (Arms B and C) | The units analyzed are the number of adverse events experienced per arm. | Posted | Count of Units | Number of Adverse Events | up to 24 months for adverse events; up to 27 months for serious adverse events | Number of Adverse Events | Number of Adverse Events |
|
up to 24 months for adverse events; up to 27 months for serious adverse events
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: HDCRT Administered With First Dose of Pembrolizumab | Pembrolizumab (200 mg) plus HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) are both administered beginning on day 1. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperuricemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. James Larner | University of Virginia | 434-982-6278 | jml2p@uvahealth.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 12, 2017 | Mar 19, 2026 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 6, 2018 | Mar 19, 2026 | ICF_001.pdf |
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| ID | Term |
|---|---|
| C582435 | pembrolizumab |
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| Pembrolizumab | Drug | 200 mg |
|
|
| BG001 | Arm B: HDCRT Administered Between Doses 1& 2 of Pembrolizumab | Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 22. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 22. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| BG002 | Arm C: HDCRT Administered Prior to First Dose of Pembrolizumab | Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 1. Pembrolizumab will be administered on days 22, 43, 64, and 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the four doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Cancer Type | Count of Participants | Participants |
|
| OG001 | ARM A Grade 2 | Grade 2 Adverse events related to ARM A study intervention. Study Intervention: Pembrolizumab (200 mg) plus HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) are both administered beginning on day 1. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG002 | ARM A Grade 3 | Grade 3 Adverse events related to ARM A study intervention. Study Intervention: Pembrolizumab (200 mg) plus HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) are both administered beginning on day 1. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG003 | ARM A Grade 4 | Grade 4 Adverse events related to ARM A study intervention. Study Intervention: Pembrolizumab (200 mg) plus HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) are both administered beginning on day 1. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG004 | ARM A Grade 5 | Grade 5 Adverse events related to ARM A study intervention. Study Intervention: Pembrolizumab (200 mg) plus HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) are both administered beginning on day 1. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG005 | ARM B Grade 1 | Grade 1 Adverse events related to ARM B study intervention. Study Intervention: Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 22. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 22. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG006 | ARM B Grade 2 | Grade 2 Adverse events related to ARM B study intervention. Study Intervention: Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 22. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 22. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG007 | ARM B Grade 3 | Grade 3 Adverse events related to ARM B study intervention. Study Intervention: Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 22. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 22. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG008 | ARM B Grade 4 | Grade 4 Adverse events related to ARM B study intervention. Study Intervention: Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 22. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 22. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG009 | ARM B Grade 5 | Grade 5 Adverse events related to ARM B study intervention. Study Intervention: Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 22. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 22. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG010 | ARM C Grade 1 | Grade 1 Adverse events related to ARM C study intervention. Study Intervention: Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 1. Pembrolizumab will be administered on days 22, 43, 64, and 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the four doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG011 | ARM C Grade 2 | Grade 2 Adverse events related to ARM C study intervention. Study Intervention: Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 1. Pembrolizumab will be administered on days 22, 43, 64, and 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the four doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG012 | ARM C Grade 3 | Grade 3 Adverse events related to ARM C study intervention. Study Intervention: Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 1. Pembrolizumab will be administered on days 22, 43, 64, and 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the four doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG013 | ARM C Grade 4 | Grade 4 Adverse events related to ARM C study intervention. Study Intervention: Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 1. Pembrolizumab will be administered on days 22, 43, 64, and 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the four doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
| OG014 | ARM C Grade 5 | Grade 5 Adverse events related to ARM C study intervention. Study Intervention: Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 1. Pembrolizumab will be administered on days 22, 43, 64, and 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the four doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg |
|
|
| Primary | Enumeration of T Cells in Tumor Tissue | Log-normalized enumeration of CD8+ T cells and FoxP3+ cells in untreated and treated tumor tissue by immunohistochemical analysis to estimate group differences and changes over time in immune assay parameters in tumor. | 14 out of the 21 subjects completed all 3 protocol required tumor biopsy and were evaluable for immunological analysis. | Posted | Mean | Standard Deviation | log(cells/ mm^2 of biopsy) | At Baseline, Day 22 of treatment, and Day 43 or treatment |
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| Secondary | Enumeration of Circulating Immune Cells | Enumeration of CD8+ and CD4+ T cells in untreated and treated blood samples to estimate group differences and changes over time in immune assay parameters in PBMC | Several participants discontinued the trial at various times, reducing the number of samples collected at later time points. | Posted | Mean | Standard Deviation | T cells/uL of blood | at Baseline and at Days 22 , 43, 64, and 85 of treatment |
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|
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| 3 |
| 7 |
| 2 |
| 7 |
| 7 |
| 7 |
| EG001 | Arm B: HDCRT Administered Between Doses 1& 2 of Pembrolizumab | Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 22. Pembrolizumab (200 mg) will be administered on days 1, 43, 64, 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the 4 doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 22. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg | 1 | 6 | 1 | 6 | 6 | 6 |
| EG002 | Arm C: HDCRT Administered Prior to First Dose of Pembrolizumab | Pembrolizumab (200 mg) begins on day 1. HDCRT (24 Gy in 3 fractions of 8 Gy each for bone and/or soft tissue lesions; 30 Gy in 5 fractions of 6 Gy each for the prostate gland) begins on day 1. Pembrolizumab will be administered on days 22, 43, 64, and 85. Subjects who have measurable disease outside of the radiation field and who have derived benefit from the four doses of pembrolizumab may continue to receive pembrolizumab every 3 weeks for up to 2 years. HDCRT will be administered to the primary tumor and/or sites of metastatic disease (1 or more sites permitted) over a period of 3-5 days. The length of time for administration of the HDCRT will depend on the site of disease that is to be radiated. HDCRT will begin on day 1. High-Dose Conformal Radiation Therapy: 24 Gy in 3 fractions of 8Gy each for bone and/or soft tissue lesions 30 Gy in 5 fractions of 6 Gy each for prostate gland Pembrolizumab: 200 mg | 3 | 8 | 2 | 8 | 8 | 8 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Blurred vision | Eye disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Confusion | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Cystitis noninfective | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Radiation Dermatitis | Injury, poisoning and procedural complications | CTCAE (4.0) | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dry eye | Eye disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| blepharitis | Eye disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Eye disorders - Other, specify | Eye disorders | CTCAE (4.0) | Non-systematic Assessment | Itchy Eyes |
|
| Fall | Injury, poisoning and procedural complications | CTCAE (4.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Fever | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Flu like symptoms | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Chest Wall pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Hematuria | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hot flashes | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypermagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Hypernatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Hypertension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hyperuricemia | Blood and lymphatic system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| INR increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Non-systematic Assessment | In various places |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Rectal pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment | folliculitis |
|
| Pulmonary embolism | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Weight loss | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
|
| CD8+ Day 22 |
|
| FoxP3 Day 22 |
|
| CD8+ Day 43 |
|
| FoxP3 Day 43 |
|
| CD4+ Baseline |
|
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| CD8+ Day 22 |
|
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| CD4+ Day 22 |
|
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| CD8+ Day 43 |
|
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| CD4+ Day 43 |
|
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| CD8+ Day 64 |
|
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| CD4+ Day 64 |
|
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| CD8+ Day 85 |
|
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| CD4+ Day 85 |
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