Evaluation of Nelfinavir and Chemoradiation for Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT01086332
• Recruitment Status: Terminated
• First Posted: March 15, 2010
• Last Update Posted: November 13, 2018
• Sponsor: University of Iowa
• Collaborator: Holden Comprehensive Cancer Center
• Information provided by (Responsible Party): Bryan Allen, University of Iowa

Tracking Information

• First Submitted Date: March 11, 2010
• First Posted Date: March 15, 2010
• Last Update Posted Date: November 13, 2018
• Study Start Date: May 2009
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2010)

Dose limiting toxicities [ Time Frame: Six weeks ]

Evaluating adverse events and their association to the treatment to determine the recommended phase II dose of gemcitabine.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 12, 2010)

Surgical resection rate [ Time Frame: 8 weeks ]

Evaluate the number of subjects who are now surgically resectable and then correlate the pathological outcomes with treatment (i.e., tumor cell kill).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Neoplasms

Intervention

• Drug: Nelfinavir
  1250 mg twice daily
  Other Name: Viracept
• Drug: Gemcitabine
  Escalating doses of gemcitabine during concurrent radiation and nelfinavir therapy.
  Other Name: Gemzar

Study Arms

Experimental: phase 1/2

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.

Interventions:

• Drug: Nelfinavir
• Drug: Gemcitabine

Publications *

• 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. Epub 2008 May 14.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 14, 2012): 7
• Original Estimated Enrollment (submitted: March 12, 2010): 70
• Actual Study Completion Date: July 2015
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
• Eligibility Criteria: Closed to accrual.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT01086332
• Other Study ID Numbers: 200905705
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data are shared upon request. Contact the clinical research team.
• Supporting Materials: Study Protocol
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Upon request
• Access Criteria: Depending upon the data desired, a confidentiality / non-disclosure agreement may be required.

• Responsible Party: Bryan Allen, University of Iowa
• Study Sponsor: University of Iowa
• Collaborators: Holden Comprehensive Cancer Center

Investigators

• Study Director: Bryan G. Allen, M.D., PhD; University of Iowa

• PRS Account: University of Iowa
• Verification Date: November 2018