Evaluation of Nelfinavir and Chemoradiation for Pancreatic Cancer

NCT ID: NCT01086332

Last Updated: 2018-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-05-31

Study Completion Date

2015-07-31

Brief Summary

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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

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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.

Conditions

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Pancreatic Neoplasms

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Nelfinavir

Intervention Type DRUG

1250 mg twice daily

Gemcitabine

Intervention Type DRUG

Escalating doses of gemcitabine during concurrent radiation and nelfinavir therapy.

Interventions

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Nelfinavir

1250 mg twice daily

Intervention Type DRUG

Gemcitabine

Escalating doses of gemcitabine during concurrent radiation and nelfinavir therapy.

Intervention Type DRUG

Other Intervention Names

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Viracept Gemzar

Eligibility Criteria

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Inclusion Criteria

Closed to accrual.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Holden Comprehensive Cancer Center

OTHER

Sponsor Role collaborator

University of Iowa

OTHER

Sponsor Role lead

Responsible Party

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Bryan Allen

Assistant Professor of Radiation Oncology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Bryan G. Allen, M.D., PhD

Role: STUDY_DIRECTOR

University of Iowa

References

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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.

Reference Type BACKGROUND
PMID: 18285707 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17460771 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16982770 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16166302 (View on PubMed)

Other Identifiers

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200905705

Identifier Type: -

Identifier Source: org_study_id

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