Evaluation of Nelfinavir and Chemoradiation for Pancreatic Cancer - Full Text View

Purpose

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	Intervention	Phase
Pancreatic Neoplasms	Drug: Nelfinavir Drug: Gemcitabine	Phase 1


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Nelfinavir Nelfinavir Mesylate

Genetic and Rare Diseases Information Center resources: Pancreatic Cancer

U.S. FDA Resources

Further study details as provided by University of Iowa:

Primary Outcome Measures:

Dose limiting toxicities [ Time Frame: Six weeks ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
Evaluate the number of subjects who are now surgically resectable and then correlate the pathological outcomes with treatment (i.e., tumor cell kill).


Enrollment:	7
Study Start Date:	May 2009
Estimated Study Completion Date:	October 2014
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Closed to accrual.

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: NCT01086332

Locations


United States, Iowa
The Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242

Sponsors and Collaborators

University of Iowa

Holden Comprehensive Cancer Center

Investigators


Study Director:	Sudershan K. Bhatia, 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:	Sudershan Bhatia, Assistant Professor of Radiation Oncology, University of Iowa
ClinicalTrials.gov Identifier:	NCT01086332 History of Changes
Other Study ID Numbers:	200905705
Study First Received:	March 11, 2010
Last Updated:	October 18, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Iowa:


radiotherapy gemcitabine nelfinavir neoplasms

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on February 27, 2015