Evaluation of Nelfinavir and Chemoradiation for Pancreatic Cancer

Study Overview
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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.

Official Title
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A Phase I/II Trial of the HIV Protease Inhibitor Nelfinavir and Concurrent Radiation and Chemotherapy in Patients With Locally Advanced Pancreatic Cancer

Conditions
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Pancreatic Neoplasms

Intervention / Treatment
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* Drug: Nelfinavir
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Closed to accrual.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: phase 1/2<br>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<br>* 1250 mg twice daily<br>* Other names: Viracept;Drug: Gemcitabine<br>* Escalating doses of gemcitabine during concurrent radiation and nelfinavir therapy.<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities | Evaluating adverse events and their association to the treatment to determine the recommended phase II dose of gemcitabine. | Six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiotherapy, gemcitabine, nelfinavir, neoplasms