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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

October 12, 2012
June 16, 2014
April 2013
July 2018   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01728779 on ClinicalTrials.gov Archive Site
  • 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.
  • To see what adverse events are experienced by participants [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    To determine the efficacy of SBRT delivered to a dose of 15 Gy in 1 fraction combined with nelfinavir in patients with oligometastatic disease by measuring clinical response rate of each lesion
  • To observe the amount of participants who do not have progression 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 combined with nelfinavir in patients with oligometastatic disease.
  • To observe the participants' clinical progress while in follow-up [ Time Frame: 2 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: 2 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: 2 years ] [ Designated as safety issue: No ]
    To determine the correlation between phospho-AKt levels and lesion response rate.
Not Provided
Not Provided
 
Stereotactic Body Radiation With Nelfinavir for Oligometastases
Single-Arm Phase II Study of Stereotactic Body Radiation Therapy Concurrent With Nelfinavir for Oligometastases

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Oligometastases
  • 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
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.
Interventions:
  • Drug: Nelfinavir
  • Radiation: Stereotactic Body Radiation (SBRT)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
42
Not Provided
July 2018   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Stephanie Terezakis, M.D. 443-287-7889 sterezak@jhmi.edu
Contact: Kelly Szajna, R.N. 410-502-9242 kszajna1@jhmi.edu
United States
 
NCT01728779
J-12137, NA_00069585
Yes
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
Not Provided
Principal Investigator: Stephanie Terezakis, M.D. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sidney Kimmel Comprehensive Cancer Center
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP