Evaluation of Nelfinavir and Chemoradiation for Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT01086332

Recruitment Status : Terminated (Toxicities, lack of funding)

First Posted : March 15, 2010

Last Update Posted : January 8, 2018

Sponsor:

Collaborator:

Holden Comprehensive Cancer Center

Information provided by (Responsible Party):

Bryan Allen, University of Iowa

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.

Condition or disease	Intervention/treatment	Phase
Pancreatic Neoplasms	Drug: Nelfinavir Drug: Gemcitabine	Phase 1

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 Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	7 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	May 2009
Actual Primary Completion Date :	July 2011
Actual Study Completion Date :	July 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pancreatic Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Nelfinavir Nelfinavir Mesylate

U.S. FDA Resources

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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.

Secondary Outcome Measures :

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).

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Closed to accrual.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01086332

Sponsors and Collaborators

University of Iowa

Holden Comprehensive Cancer Center

Investigators


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

More Information

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.


Responsible Party:	Bryan Allen, Assistant Professor of Radiation Oncology, University of Iowa
ClinicalTrials.gov Identifier:	NCT01086332 History of Changes
Other Study ID Numbers:	200905705
First Posted:	March 15, 2010 Key Record Dates
Last Update Posted:	January 8, 2018
Last Verified:	January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Data will be shared through clinicaltrials.gov

Keywords provided by Bryan Allen, University of Iowa:


radiotherapy gemcitabine nelfinavir neoplasms

Additional relevant MeSH terms:


Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Gemcitabine Nelfinavir HIV Protease Inhibitors Antimetabolites, Antineoplastic	Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Protease Inhibitors Anti-HIV Agents Anti-Retroviral Agents

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