Solid Tumors Induced by Prior Radiation Exposure
Conditions
Keywords
radiation-induced solid tumors, Nivolumab, Phase 2 study
Brief summary
The purpose of this study is to determine whether Nivolumab is effective in the treatment of radiation-induced solid tumors.
Interventions
DRUGNivolumab
Sponsors
Bristol-Myers Squibb
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed metastatic or unresectable solid tumor which standard curative or palliative measures do not exist or are no longer effective. The primary site of the metastatic or unresectable tumor must have arisen within a previously irradiated site and be considered a radiation-induced tumor. * Pre-treatment tumor specimen available. Patients with no available archived specimen must be willing to undergo a pre-treatment tumor biopsy. * Measurable disease. * Progressive disease on study entry. * Received adjuvant or neoadjuvant chemotherapy and developed recurrent or metastatic disease within 6 months of completing therapy. * Age \>18 years. * Eastern Cooperative Oncology Group (ECOG) performance status \<2. * Life expectancy of greater than 3 months. * Adequate organ and marrow function as defined below: * White Blood Cell \>2,000/per microliter * Absolute neutrophil count \>1,500/per microliter * Platelets \>100,000/per microliter * Hemoglobin ≥9.0 g/dL * Total bilirubin ≤1.5 times the institutional upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) * Aspartate Aminotransferase(SGOT)/Alanine Aminotransferase (SGPT) \<3 X institutional ULN * Creatinine ≤1.5 X institutional ULN OR * Creatinine clearance \>40 mL/min for patients with creatinine Levels above institutional normal (calculated using the Cockcroft-Gault formula below) * Female Creatinine Clearance = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL * Male Creatinine Clearance = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL * Women of childbearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry and for the duration of study participation and up to 31 weeks after the last dose of nivolumab. * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of nivolumab. * Ability to understand and the willingness to sign a written informed consent document. * Biopsiable disease at the time of enrollment as biopsies after progression are required for participation.
Exclusion criteria
* Any active, known or suspected autoimmune disease. * Requiring continuous supplemental oxygen. * Chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or unresolved toxicity due to agents administered more than 2 weeks earlier. * Uncontrolled brain metastases. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab. * Uncontrolled inter-current illness. * Pregnant or currently breastfeeding. * Receiving any other anticancer therapy. * Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA- 4 antibody therapies, any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways. * History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating ongoing acute or chronic infection. * Requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Objective Response Rate | Up to 24 weeks | Number of participants with response. Response will be assessed at baseline (within 4 weeks prior to starting nivolumab) and then every 8 weeks while on Nivolumab, up to 24 weeks. The best objective response will be assessed at 24 weeks. Response will be defined based on RECIST 1.1 criteria where complete response (CR)= disappearance of all target lesions, partial response (PR) is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Progression-free at 24 Weeks From the Time of Enrollment | 24 weeks | Disease status at 24 weeks will be compared to disease status at the time of enrollment, and response coded based on RECIST 1.1 criteria. |
| Progression-free Survival | Up to 22 months | Number of participants alive without progression. |
| Duration of Response | Up to 22 months | The duration of overall response is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, accessed up to 3 years. |
| Number of Participants With Treatment-related Adverse Events | up to 100 days post-intervention | Number of participants with treatment-related adverse events as defined by CTCAE 4.0 criteria. |
| Overall Survival | Up to 22 months | Overall survival was planned to be measured at 5 years post-intervention as the time from enrollment until death. Instead, due to early termination for low accrual, the number of participants alive at the time of study termination is reported. |
Countries
United States
Participant flow
Pre-assignment details
2 subjects were screen failures
Participants by arm
| Arm | Count |
|---|---|
| Radiation-Induced Metastatic Sarcoma a flat dose of Nivolumab 240 mg will be administered intravenously every 2 weeks until disease progression.
Nivolumab | 2 |
| Radiation-Induced Non-Sarcoma Metastatic Solid Tumors a flat dose of Nivolumab 240 mg will be administered intravenously every 2 weeks until disease progression.
Nivolumab | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Progressive Disease | 2 | 1 |
Baseline characteristics
| Characteristic | Radiation-Induced Metastatic Sarcoma | Radiation-Induced Non-Sarcoma Metastatic Solid Tumors | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 2 / 2 |
| other Total, other adverse events | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 1 / 2 | 1 / 2 |
Outcome results
Primary
Best Objective Response Rate
Number of participants with response. Response will be assessed at baseline (within 4 weeks prior to starting nivolumab) and then every 8 weeks while on Nivolumab, up to 24 weeks. The best objective response will be assessed at 24 weeks. Response will be defined based on RECIST 1.1 criteria where complete response (CR)= disappearance of all target lesions, partial response (PR) is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.
Time frame: Up to 24 weeks
Population: Data was not collected for 1/2 participants from the non-sarcoma arm since the participant was discontinued from therapy (due to adverse event) before disease re-evaluation for response could be performed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiation-Induced Metastatic Sarcoma | Best Objective Response Rate | PD | 2 Participants |
| Radiation-Induced Metastatic Sarcoma | Best Objective Response Rate | SD | 0 Participants |
| Radiation-Induced Metastatic Sarcoma | Best Objective Response Rate | PR | 0 Participants |
| Radiation-Induced Metastatic Sarcoma | Best Objective Response Rate | CR | 0 Participants |
| Radiation-Induced Non-Sarcoma Metastatic Solid Tumors | Best Objective Response Rate | CR | 0 Participants |
| Radiation-Induced Non-Sarcoma Metastatic Solid Tumors | Best Objective Response Rate | PD | 1 Participants |
| Radiation-Induced Non-Sarcoma Metastatic Solid Tumors | Best Objective Response Rate | PR | 0 Participants |
| Radiation-Induced Non-Sarcoma Metastatic Solid Tumors | Best Objective Response Rate | SD | 0 Participants |
Secondary
Duration of Response
The duration of overall response is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, accessed up to 3 years.
Time frame: Up to 22 months
Population: Data was not collected to assess this outcome measure since none of the participants experienced a response.
Secondary
Number of Participants With Treatment-related Adverse Events
Number of participants with treatment-related adverse events as defined by CTCAE 4.0 criteria.
Time frame: up to 100 days post-intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation-Induced Metastatic Sarcoma | Number of Participants With Treatment-related Adverse Events | 2 Participants |
| Radiation-Induced Non-Sarcoma Metastatic Solid Tumors | Number of Participants With Treatment-related Adverse Events | 2 Participants |
Secondary
Overall Survival
Overall survival was planned to be measured at 5 years post-intervention as the time from enrollment until death. Instead, due to early termination for low accrual, the number of participants alive at the time of study termination is reported.
Time frame: Up to 22 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation-Induced Metastatic Sarcoma | Overall Survival | 1 Participants |
| Radiation-Induced Non-Sarcoma Metastatic Solid Tumors | Overall Survival | 0 Participants |
Secondary
Percentage of Patients Progression-free at 24 Weeks From the Time of Enrollment
Disease status at 24 weeks will be compared to disease status at the time of enrollment, and response coded based on RECIST 1.1 criteria.
Time frame: 24 weeks
Population: Data was not collected to assess this outcome measure since no participants remained on the study at 24 weeks.
Secondary
Progression-free Survival
Number of participants alive without progression.
Time frame: Up to 22 months
Population: Data was not collected for 1/2 participants from the non-sarcoma arm since the participant was discontinued from therapy (due to adverse event) before disease re-evaluation for response could be performed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation-Induced Metastatic Sarcoma | Progression-free Survival | 0 Participants |
| Radiation-Induced Non-Sarcoma Metastatic Solid Tumors | Progression-free Survival | 0 Participants |