Stereotactic Body Radiation With Nelfinavir for Oligometastases

Phase 2

Completed

Conditions: Oligometastases

Interventions: Drug: Nelfinavir
Radiation: Stereotactic Body Radiation (SBRT)

Registration Number: NCT01728779

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 38

Inclusion Criteria

Not provided

Exclusion Criteria

Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study
Patients receiving any other investigational agents
Patient who has had any prior radiotherapy to the treatment site(s)
Patients taking drugs that are contraindicated with nelfinavir, including any of the following:

Amiodarone, Quinidine, Rifampin, Dihydroergotamine, Ergonovine, Ergotamine, Methylergonovine, Hypericum perforatum (St. John's wort), Lovastatin, Simvastatin, Pimozide, Midazolam, Triazolam

Women of child bearing potential who refuse to take a pregnancy test prior to treatment
Participation in another concurrent treatment protocol while being treated on this protocol and through to 3 months after treatment on this protocol has ended
Pregnant women
Inability to understand the informed consent document
Inability to sign the informed consent document
Poor liver function suggestive of cirrhosis or steatohepatitis

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)	Stereotactic Body Radiation (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.
Nelfinavir w/Stereotactic Body Radiation Therapy (SBRT)	Nelfinavir	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Freedom From Local Progression (FFLP)	6 months	To determine the 6-month Freedom From Local Progression rate (measured as a percentage of participants) in participants treated with radiosensitizer nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction in patients with oligometastatic disease. FFLP is defined as the percent of participants who were free from progression at the 6 month time point.

Secondary Outcome Measures

Name	Time	Method
Total Number of Adverse Events Experienced by Participants	1 year	To assess the toxicity of the radiosensitizer Nelfinavir used concurrently with 15 Gy of stereotactic body radiation therapy (SBRT) delivered in 1 fraction (per lesion site) in patients with oligometastatic disease. Toxicity is assessed by the total number of adverse events based on Common Terminology Criteria for Adverse Events (CTCAE).
Percent of Lesions With Local Control at 6 Months Post-treatment	6 months	To determine percent of lesions with 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.
Phospho/ Akt Levels With Respect to Lesion Response	3 months	Assess phospho-Akt protein in study participants to determine whether there is a correlation between the level protein and improved lesion response rate.
Participants' Clinical Progress While in Follow-up in Terms of Survival	18 months	To assess the long-term clinical outcomes of this patient population after completion of SBRT in combination with Nelfinavir by determining the percentage of participants with Overall Survival (OS), Freedom From Distant Metastasis (FFDM) and the Progression-Free Survival (PFS).
Quality of Life After Completion of Treatment	3 years	To assess quality of life following completion of SBRT in combination with nelfinavir