Stereotactic Body Radiation With Nelfinavir for Oligometastases

NCT ID: NCT01728779

Last Updated: 2021-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-08
• Study Completion Date: 2020-12-31

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.

Conditions

Oligometastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Nelfinavir

Intervention Type: DRUG

Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.

Stereotactic Body Radiation (SBRT)

Intervention Type: RADIATION

15 Gy dose (per lesion site) of SBRT will be administered

Interventions

Nelfinavir

Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.

Intervention Type: DRUG

Stereotactic Body Radiation (SBRT)

15 Gy dose (per lesion site) of SBRT will be administered

Intervention Type: RADIATION

Other Intervention Names

Viracept; Stereotactic Body Radiation; SBRT

Eligibility Criteria

Inclusion Criteria

• Patient's tumor(s) to be treated is(are) ≤ 5.0 cm or ≤250 cm3
• Patient must have metastasis at one or more of the following sites: bone, liver, lymph node and/or lung. No more than five lesions will be treated.
• Histological confirmation of malignancy (primary or metastatic tumor).

Exclusion Criteria

• Patient must be ≥ 18 years of age.
• Patient must have a life expectancy ≥ 9 months.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Patient must have normal organ and marrow function.
• Patient must have the ability to understand and the willingness to sign a written informed consent document.

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Phuoc Tran, M.D.

Role: PRINCIPAL_INVESTIGATOR

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NA_00069585

Identifier Type: OTHER

Identifier Source: secondary_id

J12137

Identifier Type: -

Identifier Source: org_study_id