Pancreatic NeoplasmsPhase 1NCT01086332
Evaluation of Nelfinavir and Chemoradiation for Pancreatic Cancer
A Phase 1 study testing Nelfinavir and Gemcitabine in people with Pancreatic Neoplasms, run by University of Iowa.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Neoplasms
- What is being tested?
- Nelfinavir and Gemcitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- No sites listed yet
- Study dates
- May 2009to Jul 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Closed to accrual.
About this study
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
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.
Read the 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.
- Conditions
- Pancreatic Neoplasms
- Being tested
- Nelfinavir, Gemcitabine
- Keywords
- radiotherapy, gemcitabine, nelfinavir, neoplasms
- Medical subject headings
- Pancreatic Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NelfinavirDrug
Also called Viracept
1250 mg twice daily
GemcitabineDrug
Also called Gemzar
Escalating doses of gemcitabine during concurrent radiation and nelfinavir therapy.
| Study group | Role | What they receive |
|---|---|---|
| phase 1/2 | Experimental | 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. Receives: Drug: Nelfinavir; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities
Evaluating adverse events and their association to the treatment to determine the recommended phase II dose of gemcitabine.
Measured: Six weeks
Secondary outcomes (1)
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).
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2010 (estimated)
- Study startMay 2009
- Primary completionJul 2011
- Study completionJul 2015
Why it stopped: Toxicities, lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pancreatic NeoplasmsStudies of the same condition, open and under way.
- More trials run by University of IowaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- Holden Comprehensive Cancer Center
- Responsible party
- Principal investigator, Bryan Allen, University of Iowa
- Investigators
- Bryan G. Allen, M.D., PhD, Study director, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01086332
- Sponsor's protocol ID
- 200905705
- Status last verified
- Nov 2018
- First submitted
- 11 Mar 2010
- Last updated
- 13 Nov 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data are shared upon request. Contact the clinical research team.
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. doi: 10.4161/cbt.7.5.5728. Epub 2008 May 14.
PubMed 18285707Gupta 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.
PubMed 17460771Pore 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.
PubMed 16982770Gupta 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.
PubMed 16166302
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01086332
- Acronym / sponsor ID
- 200905705
- Conditions
- Pancreatic Neoplasms
- Keywords
- radiotherapy, gemcitabine, nelfinavir, neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Toxicities, lack of funding
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- Holden Comprehensive Cancer Center
- Study start
- May 2009
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 15 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| phase 1/2 | Experimental | Drug: Nelfinavir, Drug: GemcitabineAn 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NelfinavirAlso: Viracept1250 mg twice daily | Drug | phase 1/2 |
| GemcitabineAlso: GemzarEscalating doses of gemcitabine during concurrent radiation and nelfinavir therapy. | Drug | phase 1/2 |
Primary outcome
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.
1 secondary outcome
Surgical resection rate
Time frame: 8 weeks
Results and safety
The study was stopped early (reason given: Toxicities, lack of funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2018.
- Background: PubMed 18285707Plastaras 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.
- Background: PubMed 17460771Gupta 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.
- Background: PubMed 16982770Pore 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.
- Background: PubMed 16166302Gupta 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.
- Individual participant dataSharing planned: Yes. Data are shared upon request. Contact the clinical research team.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bryan G. Allen, M.D., PhD study director
University of Iowa
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nelfinavir and Gemcitabine in people with Pancreatic Neoplasms, run by University of Iowa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Toxicities, lack of funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicities (time frame: Six weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01086332, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2018.