Stereotactic Body Radiation With Nelfinavir for Oligometastases
Radiation: Stereotactic Body Radiation (SBRT)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Single-Arm Phase II Study of Stereotactic Body Radiation Therapy Concurrent With Nelfinavir for Oligometastases|
- To document the number of participants that do not have progression at the 6 months post treatment time frame [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]To determine the 6-month progression free survival rate of the radiosensitizer nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction in patients with oligometastatic disease.
- To see what adverse events are experienced by participants [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]To assess the toxicity of the radiosensitizer Nelfinavir used concurrently with 15Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction (per lesion site) in patients with oligometastatic disease.
- To observe the amount of participants who have local control 6 months post-treatment [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]To determine local control at 6-months after SBRT delivered to a dose of 15 Gy in 1 fraction (per lesion site) combined with nelfinavir in patients with oligometastatic disease.
- To observe the participants' clinical progress while in follow-up [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]To assess the long-term clinical outcomes of this patient population after completion of SBRT in combination with Nelfinavir.
- Quality of Life [ Time Frame: 3 years ] [ Designated as safety issue: No ]To assess quality of life following completion of SBRT in combination with nelfinavir
- Phospho/ Akt levels with respect to lesion response [ Time Frame: 3 months ] [ Designated as safety issue: No ]To determine the correlation between phospho-Akt levels and lesion response rate.
|Study Start Date:||April 2013|
|Estimated Primary Completion Date:||July 2018 (Final data collection date for primary outcome measure)|
Experimental: Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)
Patients with metastatic lesions of the lung, liver, or bone will be candidates for treatment. Within three weeks of the initial treatment planning, a 15 Gy dose (per lesion site) of SBRT will be administered. Prior to SBRT, patients will initiate Nelfinavir oral therapy twice daily for 7 days. Once SBRT is completed, the patient will repeat the same Nelfinavir therapy for an additional 7 days for a total of 14 days of treatment.
Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.
Other Name: ViraceptRadiation: Stereotactic Body Radiation (SBRT)
15 Gy dose (per lesion site) of SBRT will be administered
The use of radiation therapy to treat metastatic tumors is well established and promising data are emerging with the use of SBRT for metastatic disease. However, the use of a single large fraction concurrent with a radiosensitizer as is being proposed is not of proven benefit. This investigation aims to confirm the safety and efficacy for SBRT used concurrently with a radiosensitizer in the setting of oligometastatic disease. The dose selected has been chosen with the belief that it is safe and effective based on prior experience with SBRT of lung cancer, pancreatic cancer and brain radiosurgery. All patients will be treated with a single fraction (per lesion site), targeted to the lesion concurrently with the radiosensitizer Nelfinavir.
On the basis of this preclinical evidence, we propose a phase II study of Nelfinavir combined with SBRT in patients with oligometastatic disease. Because the standard dose of Nelfinavir for HIV patients is known to be safe and does inhibit the phosphorylation of Akt and decrease tumor hypoxia, we propose to study this in conjunction with a 15 Gy dose of SBRT. Experience with single-fraction pulmonary and pancreas SBRT provides a useful dose for this trial. With published data establishing the relative safety of large single-fraction SBRT to the lungs and pancreas, we have decided to proceed to determine the safety of 15 Gy SBRT concurrently with the radiosensitizer Nelfinavir. Once this is established, we propose to continue to enroll more patients to the study at this dose to determine the efficacy of this type of therapy.
The proposed study represents an informed estimate based on current knowledge of SBRT doses and those administered in currently approved image-guided protocols (brain, base of skull, cervico-thoracic spine, pancreas and liver). This study will refine the current understanding of single fraction radiation tolerance for normal tissues, thereby making it possible to treat future patients more safely and aggressively.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01728779
|United States, Maryland|
|The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231|
|Principal Investigator:||Stephanie Terezakis, M.D.||The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|