Evaluation of Nelfinavir and Chemoradiation for Pancreatic Cancer
Primary Purpose
Pancreatic Neoplasms
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Nelfinavir
Gemcitabine
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Neoplasms focused on measuring radiotherapy, gemcitabine, nelfinavir, neoplasms
Eligibility Criteria
Closed to accrual.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
phase 1/2
Arm Description
An escalating study of gemcitabine when combined with 1250 mg of nelfinavir twice daily. Dose of gemcitabine is increased for new subjects based on the experiences and tolerance of prior subjects. When the maximum tolerated dose is identified, a recommended phase 2 dose will be assigned and further subjects will receive that dose.
Outcomes
Primary Outcome Measures
Dose limiting toxicities
Evaluating adverse events and their association to the treatment to determine the recommended phase II dose of gemcitabine.
Secondary Outcome Measures
Surgical resection rate
Evaluate the number of subjects who are now surgically resectable and then correlate the pathological outcomes with treatment (i.e., tumor cell kill).
Full Information
NCT ID
NCT01086332
First Posted
March 11, 2010
Last Updated
November 8, 2018
Sponsor
University of Iowa
Collaborators
Holden Comprehensive Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT01086332
Brief Title
Evaluation of Nelfinavir and Chemoradiation for Pancreatic Cancer
Official Title
A Phase I/II Trial of the HIV Protease Inhibitor Nelfinavir and Concurrent Radiation and Chemotherapy in Patients With Locally Advanced Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Terminated
Why Stopped
Toxicities, lack of funding
Study Start Date
May 2009 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Iowa
Collaborators
Holden Comprehensive Cancer Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is designed to evaluate if nelfinavir works as a radiation sensitizer in combination with gemcitabine (a chemotherapy). We are also looking to establish the maximum dose of gemcitabine that is tolerated with the nelfinavir and radiation therapy, so the dose of gemcitabine is increased based on how previous trial participants tolerated their dose of gemcitabine.
Detailed Description
This trial utilizes gemcitabine (a chemotherapy agent commonly used for pancreatic cancer) and nelfinavir (an anti-retroviral agent FDA-approved for use in HIV+ patients) in addition to radiation therapy for treatment of borderline resectable pancreatic cancer. The trial seeks to determine the maximum tolerated dose of gemcitabine when administered concurrently with radiation therapy and 1250 mg nelfinavir twice daily.
The gemcitabine and radiation is standard; the dose of gemcitabine does vary nationally and internationally as to what the 'best dose' is. Administered weekly, doses can range from 400 mg/m2 to 1000 mg/m2. Thus, this is why the proposed clinical trial escalates the gemcitabine.
The gemcitabine will be administered weekly during radiation therapy for a total of 6 cycles. After completion of radiation therapy, the subjects will be evaluated by the surgeons for resectability. This ends the active portion of the clinical trial; the subjects will be followed for long-term progression free survival and for overall survival.
Primary endpoints for this trial are identifying the maximum tolerated dose of gemcitabine when administered concurrently with nelfinavir and radiation therapy (the phase I portion of this study) and the rate of resectability (typically, utilizing gemcitabine plus radiation therapy will convert up to 30% of patients from borderline resectable to resectable) for the phase II portion of the study.
Interim analyses and stopping rules are in place if an effect size is not observed in the therapeutic group compared to published reports of response to standard chemoradiation for borderline resectable cases.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Neoplasms
Keywords
radiotherapy, gemcitabine, nelfinavir, neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
phase 1/2
Arm Type
Experimental
Arm Description
An escalating study of gemcitabine when combined with 1250 mg of nelfinavir twice daily. Dose of gemcitabine is increased for new subjects based on the experiences and tolerance of prior subjects. When the maximum tolerated dose is identified, a recommended phase 2 dose will be assigned and further subjects will receive that dose.
Intervention Type
Drug
Intervention Name(s)
Nelfinavir
Other Intervention Name(s)
Viracept
Intervention Description
1250 mg twice daily
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
Escalating doses of gemcitabine during concurrent radiation and nelfinavir therapy.
Primary Outcome Measure Information:
Title
Dose limiting toxicities
Description
Evaluating adverse events and their association to the treatment to determine the recommended phase II dose of gemcitabine.
Time Frame
Six weeks
Secondary Outcome Measure Information:
Title
Surgical resection rate
Description
Evaluate the number of subjects who are now surgically resectable and then correlate the pathological outcomes with treatment (i.e., tumor cell kill).
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Closed to accrual.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bryan G. Allen, M.D., PhD
Organizational Affiliation
University of Iowa
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data are shared upon request. Contact the clinical research team.
IPD Sharing Time Frame
Upon request
IPD Sharing Access Criteria
Depending upon the data desired, a confidentiality / non-disclosure agreement may be required.
Citations:
PubMed Identifier
18285707
Citation
Plastaras JP, Vapiwala N, Ahmed MS, Gudonis D, Cerniglia GJ, Feldman MD, Frank I, Gupta AK. Validation and toxicity of PI3K/Akt pathway inhibition by HIV protease inhibitors in humans. Cancer Biol Ther. 2008 May;7(5):628-35. doi: 10.4161/cbt.7.5.5728. Epub 2008 May 14.
Results Reference
background
PubMed Identifier
17460771
Citation
Gupta AK, Li B, Cerniglia GJ, Ahmed MS, Hahn SM, Maity A. The HIV protease inhibitor nelfinavir downregulates Akt phosphorylation by inhibiting proteasomal activity and inducing the unfolded protein response. Neoplasia. 2007 Apr;9(4):271-8. doi: 10.1593/neo.07124.
Results Reference
background
PubMed Identifier
16982770
Citation
Pore N, Gupta AK, Cerniglia GJ, Jiang Z, Bernhard EJ, Evans SM, Koch CJ, Hahn SM, Maity A. Nelfinavir down-regulates hypoxia-inducible factor 1alpha and VEGF expression and increases tumor oxygenation: implications for radiotherapy. Cancer Res. 2006 Sep 15;66(18):9252-9. doi: 10.1158/0008-5472.CAN-06-1239.
Results Reference
background
PubMed Identifier
16166302
Citation
Gupta AK, Cerniglia GJ, Mick R, McKenna WG, Muschel RJ. HIV protease inhibitors block Akt signaling and radiosensitize tumor cells both in vitro and in vivo. Cancer Res. 2005 Sep 15;65(18):8256-65. doi: 10.1158/0008-5472.CAN-05-1220.
Results Reference
background
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Evaluation of Nelfinavir and Chemoradiation for Pancreatic Cancer
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