Solid Tumor
Conditions
Keywords
immunotherapy, pembrolizumab, MK-3475, High-dose conformal radiation therapy, HDCRT, advanced solid tumor
Brief summary
This study is a pilot study to evaluate high-dose conformal radiation therapy (HDCRT) administered in combination with pembrolizumab in patients with solid tumors.
Interventions
RADIATIONHigh-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
DRUGPembrolizumab
200 mg
Sponsors
James Larner, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: * Patients must be resistant to at least 1 prior conventional chemotherapy regimen or other standard of care regimen, * Patient must have no remaining conventional treatment options proven to provide long-term disease control, and * Patient has declined other conventional treatment options * 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
* Requires urgent treatment with cytotoxic chemotherapy or other therapy is indicated. * A diagnosis of immunodeficiency. * A known history of active TB (Bacillus Tuberculosis). * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with untreated brain metastases and patients who have had brain metastases re-treated with radiation will be excluded. Patients whom have either midline shift, or any signs of herniation (even if disease has been treated with GK) will be excluded. Subjects with previously treated brain metastases may participate provided they are 1) stable (without clinical evidence of progression) 2) are out at least 10 days from CNS radiation and 3) and are not using steroids as part of treatment for their brain lesions for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. * Active autoimmune disease that has required systemic treatment in the past 2 years. * A history of (non-infectious) pneumonitis that required steroids or current pneumonitis. * An infection requiring systemic therapy. * Pregnancy. * HIV positivity. * Evidence of active Hepatitis B virus or Hepatitis C virus. * Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, uncontrolled arrhythmias, or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment. * Active bleeding disorders or evidence of chronic or acute disseminated intravascular coagulation (DIC). * Class III or IV heart disease (New York Heart Association classification).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Adverse Event Profile | up to 24 months for adverse events; up to 27 months for serious adverse events | Adverse events related to HDCRT with immunotherapy, delivered concurrently (Arm A) or sequentially (Arms B and C) |
| Enumeration of T Cells in Tumor Tissue | At Baseline, Day 22 of treatment, and Day 43 or treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Enumeration of Circulating Immune Cells | at Baseline and at Days 22 , 43, 64, and 85 of treatment | 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 |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJames Larner, MD
University of Virginia
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Cancer Type Breast Cancer | 1 Participants |
| Cancer Type Colon Cancer | 1 Participants |
| Cancer Type GE Junctional Cancer | 1 Participants |
| Cancer Type Head and Neck Cancer | 1 Participants |
| Cancer Type Leiomyosarcoma | 0 Participants |
| Cancer Type Melanoma | 1 Participants |
| Cancer Type Pancreatic Cancer | 0 Participants |
| Cancer Type Testicular Cancer | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 7 | 1 / 6 | 3 / 8 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 8 / 8 |
| serious Total, serious adverse events | 2 / 7 | 1 / 6 | 2 / 8 |
Outcome results
None listed