Metastatic Carcinoma
Conditions
Keywords
radiation
Brief summary
This is an open label single arm phase 2 clinical trial in patients with metastatic solid malignancy of any histology who have previously experienced limited progression in at least 1 and up to 5 lesions while on immune checkpoint inhibitors monotherapy.
Detailed description
All potential subjects are required to undergo screening evaluation to determine eligibility within 28 days of study enrollment. Eligible subjects will continue the same immune checkpoint inhibitors on which they experienced limited progression and will also receive radiation therapy. radiation therapy for all subjects will consist of treating one tumor of the treating physician's preference, and after a 1-week interval during which immune checkpoint inhibitor is continued alone, radiation therapy will be given to a second and separate tumor. No additional radiation therapy will be delivered. immune checkpoint inhibitors will be continued until disease progression or unacceptable toxicity. Diagnostic imaging studies will be performed to determine treatment response at baseline/screening, 8 weeks after initiation of radiation therapy to the first lesion and every 8 weeks thereafter. Peripheral blood mononuclear cell composition will be evaluated at various time points within 14 days of starting radiation therapy, on Day 8 (1 week after starting radiation therapy to the first lesion), Day 23 (1 week after starting radiation therapy to the second lesion), and 8 weeks after treatment initiation. A total of 52 subjects will be enrolled on this trial. The expected rate of accrual is 2 patients per month at a single institution over 26 months.
Interventions
RADIATIONRadiation Therapy
Radiation therapy for all subjects will consist of treating one tumor of the treating physician's preference (40 Gray (Gy) in 5 fractions), and after a 1-week interval during which ICI is continued alone, radiation therapy will be given to a second and separate tumor (30 Gy in 5 fractions).
Sponsors
Viewray Inc.
Baptist Health South Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Radiation therapy for all subjects will consist of treating one tumor of the treating physician's preference (40 Gray (GY) in 5 fractions), and after a 1-week interval during which Immune checkpoint inhibitor is continued alone, radiation therapy will be given to a second and separate tumor (30 Gy in 5 fractions).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age at the time of study entry. 2. Eastern Cooperative Oncology Group performance status of 0, 1, or 2. 3. Life expectancy of .12 weeks as estimated by the treating physician. 4. Metastatic carcinoma confirmed by biopsy or imaging study if biopsy is not deemed feasible. 5. Most recent anti-cancer therapy consists of a single ICI drug including but not limited to ipilimumab, nivolumab, pembrolizumab, atezolizumab. 6. Radiographic evidence of progression while on a single ICI drug in 1 and up to 5 lesions. 7. Eligible to continue ICI during and after radiation therapy. 8. 3 radiographically distinct and measurable lesions (primary and/or metastatic lesions) by RECIST 1.1 criteria, with .3 lesions separated from each other by .5 cm 9. Subjects must consent to all study procedures described in the protocol including radiographic evaluation and blood draws. 10. Immunosuppressive doses of systemic medication including steroids must be discontinued at least 14 days prior to the start of radiation therapy. 11. Adequate normal organ and marrow function 12. Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: .60 years old and no menses for .1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy), have a negative serum pregnancy test within 14 days of study enrollment, and not be breastfeeding.
Exclusion criteria
1. Any contraindication to having an MRI scan. 2. Chemotherapy, biologic agent, investigational therapy, or radiation therapy given within 14 days of study enrollment. 3. Symptomatic or uncontrolled brain metastasis requiring treatment. 4. The need for palliative radiation therapy to a non-target lesion prior to radiation therapy to one of 2 target lesion on this study. 5. Prior radiation therapy to any lesion that would receive radiation therapy on this protocol. 6. Prior radiation therapy to a lesion located within 4 cm of previously irradiated structures: spinal cord that previously received \>45 Gy; brachial plexus that previously received \>45 Gy; small/large intestine or stomach that previously received \>45 Gy; prior total lung V20 \>30%. 7. Prior radiation therapy that could lead to an unacceptably high risk of clinically significant normal tissue injury due to high cumulative normal tissue dose as determined by the investigator. 8. History of any primary malignancy with the exception of 1. Malignancy treated with curative intent and with no known active disease for at least 3 years before enrollment on this study. 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. 3. Adequately treated carcinoma in situ without evidence of disease (i.e. cervical carcinoma in situ; superficial bladder cancer). 9. Any unresolved toxicity (Common Terminology Criteria for Adverse Events version 5.0 \> grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to worsen by treatment on this study are permitted to enroll on this study. 10. Active or prior documented autoimmune disease within the past 2 years. Subjects with vitiligo, type I diabetes mellitus, Graves disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. 11. Subjects requiring systemic corticosteroid (\>10 mg daily prednisone equivalent) or other immunosuppressive medication within 14 days of study enrollment. 12. Contraindication to IV contrast despite premedication for iodine allergy, which would limit the ability to assess radiographic response to study treatment. 13. Prior allogeneic organ transplantation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Overall Response Rate (ORR) According to RECIST 1.1 Criteria | 6 months | ORR is defined as the percent of participants who have a partial response (PR) or complete response (CR) to therapy of non-irradiated lesions according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria assessed on CT imaging. CR is defined as the disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease from baseline in the sum of the longest diameters of target lesions AND for non-target lesions, no progression of existing lesions or appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Related Adverse Events | through study completion, an average of 1 year | Treatment related adverse events are defined as those possibly, probably, or definitely related to the study treatment. These events will be tabulated and reported by grade of severity. |
| Change in Immune-related ORR (irORR) According to Immune-related Response Criteria (irRC) | 6 month | irORR is the percent of patients with best overall response of irCR or irPR from the start of the study until 6 months later. Only index and measurable new lesions are taken into account in irRC and response is defined over at least 4 weeks. irCR is defined as the disappearance of all lesions in two observations at least 4 weeks apart. irPR is defined as at least 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart. |
| Duration of Response | 6 month | Duration of response is defined as the time from when CR or PR is first determined until the first date of documented progressive disease (PD) or death, whichever occurs first. |
| Overall Survival (OS) | 2 years | OS is defined as the percent of participants who are alive at the end of the study. Death due to any cause will be considered. |
| Progression-free Survival (PFS) | 6 month | PFS is defined as the amount of time from first treatment to disease progression or death from any cause. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiation Therapy (RT) RT for all subjects will consist of treating one tumor of the treating physician's preference (40 Gy in 5 fractions), and after a 1-week interval during which Immune checkpoint inhibitor (ICI) is continued alone, RT will be given to a second and separate tumor (30 Gy in 5 fractions).
Radiation Therapy: Radiation therapy for all subjects will consist of treating one tumor of the treating physician's preference (40 Gray (Gy) in 5 fractions), and after a 1-week interval during which ICI is continued alone, radiation therapy will be given to a second and separate tumor (30 Gy in 5 fractions). | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Deemed ineligible after being enrolled | 1 |
Baseline characteristics
| Characteristic | Radiation Therapy (RT) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 64.92 years STANDARD_DEVIATION 9.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 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 | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 11 |
| other Total, other adverse events | 9 / 11 |
| serious Total, serious adverse events | 3 / 11 |
Outcome results
Primary
Change in Overall Response Rate (ORR) According to RECIST 1.1 Criteria
ORR is defined as the percent of participants who have a partial response (PR) or complete response (CR) to therapy of non-irradiated lesions according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria assessed on CT imaging. CR is defined as the disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease from baseline in the sum of the longest diameters of target lesions AND for non-target lesions, no progression of existing lesions or appearance of new lesions.
Time frame: 6 months
Population: Six participants did not receive 6-month imaging and response evaluation. Five were taken off study due to disease progression (two), new AE that made them ineligible to continue (one), other ineligibility (one), or expiration (one). One participant had missed imaging.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation Therapy (RT) | Change in Overall Response Rate (ORR) According to RECIST 1.1 Criteria | 1 Participants |
Secondary
Change in Immune-related ORR (irORR) According to Immune-related Response Criteria (irRC)
irORR is the percent of patients with best overall response of irCR or irPR from the start of the study until 6 months later. Only index and measurable new lesions are taken into account in irRC and response is defined over at least 4 weeks. irCR is defined as the disappearance of all lesions in two observations at least 4 weeks apart. irPR is defined as at least 50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart.
Time frame: 6 month
Population: Six participants did not receive 6-month imaging and response evaluation. Five were taken off study due to disease progression (two), new AE that made them ineligible to continue (one), other ineligibility (one), or expiration (one). One participant had missed imaging.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation Therapy (RT) | Change in Immune-related ORR (irORR) According to Immune-related Response Criteria (irRC) | 1 Participants |
Secondary
Duration of Response
Duration of response is defined as the time from when CR or PR is first determined until the first date of documented progressive disease (PD) or death, whichever occurs first.
Time frame: 6 month
Population: Only two participants ever had PR. None had CR. Out of the two participants with PR, one did not have progression during the time points when response was assessed, thus was not included in this calculation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiation Therapy (RT) | Duration of Response | 55 days |
Secondary
Number of Treatment Related Adverse Events
Treatment related adverse events are defined as those possibly, probably, or definitely related to the study treatment. These events will be tabulated and reported by grade of severity.
Time frame: through study completion, an average of 1 year
Population: One participant was deemed ineligible after being considered enrolled and was thus withdrawn.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiation Therapy (RT) | Number of Treatment Related Adverse Events | Mild (Grade 1) | 19 events |
| Radiation Therapy (RT) | Number of Treatment Related Adverse Events | Moderate (Grade 2) | 7 events |
| Radiation Therapy (RT) | Number of Treatment Related Adverse Events | Severe (Grade 3) | 6 events |
| Radiation Therapy (RT) | Number of Treatment Related Adverse Events | Life-threatening (Grade 4) | 0 events |
| Radiation Therapy (RT) | Number of Treatment Related Adverse Events | Death (Grade 5) | 0 events |
Secondary
Overall Survival (OS)
OS is defined as the percent of participants who are alive at the end of the study. Death due to any cause will be considered.
Time frame: 2 years
Population: One participant was deemed ineligible after being considered enrolled and was thus withdrawn.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation Therapy (RT) | Overall Survival (OS) | 5 Participants |
Secondary
Progression-free Survival (PFS)
PFS is defined as the amount of time from first treatment to disease progression or death from any cause.
Time frame: 6 month
Population: One participant was deemed ineligible after being considered enrolled and was thus withdrawn.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiation Therapy (RT) | Progression-free Survival (PFS) | 2.5 months |