Stereotactic Body Radiation With Nelfinavir for Oligometastases

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01728779
First received: October 12, 2012
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Oligometastases
Drug: Nelfinavir
Radiation: Stereotactic Body Radiation (SBRT)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 42
Study Start Date: April 2013
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Nelfinavir
Commercially available nelfinavir (1250 mg) will be administered orally twice daily for 14 days.
Other Name: Viracept
Radiation: Stereotactic Body Radiation (SBRT)
15 Gy dose (per lesion site) of SBRT will be administered
Other Names:
  • Stereotactic Body Radiation
  • SBRT

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  • Patient may have any prior therapy allowed aside from having had prior radiotherapy to the treatment site (see exclusion criteria 5.2.3).
  • Patient must be ≥ 18 years of age.
  • Patient must have a life expectancy ≥ 9 months.
  • Patient must have an 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.

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study
  • Patients receiving any other investigational agents
  • Pateitnw ho 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01728779

Contacts
Contact: Stephanie Terezakis, M.D. 443-287-7889 sterezak@jhmi.edu
Contact: Kelly Szajna, R.N. 410-502-9242 kszajna1@jhmi.edu

Locations
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: Stephanie Terezakis, M.D.    443-287-7889    sterezak@jhmi.edu   
Contact: Kelly Szajna, R.N.    410-614-3950    kszajna1@jhmi.edu   
Sub-Investigator: Deborah Frassica, M.D.         
Sub-Investigator: Russell Hales, M.D.         
Sub-Investigator: Joseph Herman, M.D.         
Sub-Investigator: Lawrence Kleinberg, M.D.         
Sub-Investigator: Michael Lim, M.D.         
Sub-Investigator: Kristin Redmond, M.D.         
Sub-Investigator: Danny Song, M.D.         
Sub-Investigator: Phuoc Tran, M.D., Ph.D.         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Stephanie Terezakis, M.D. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01728779     History of Changes
Other Study ID Numbers: J-12137, NA_00069585
Study First Received: October 12, 2012
Last Updated: June 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Nelfinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 01, 2014