Solid TumorsPhase 1NCT01445106
A Phase I Trial of Nelfinavir (Viracept ) in Adults With Solid Tumors
A Phase 1 study testing Nelfinavir and Nelfinavir Mesylate in people with Solid Tumors, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: The PI3K/Akt/mTOR pathway is an important target in cancer because it promotes chemotherapeutic resistance and confers a poor prognosis for many types of cancers. Several inhibitors of the pathway are being developed as cancer therapeutics. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- Nelfinavir and Nelfinavir Mesylate
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Dec 2006to 9 May 2011
- 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
Who may be able to join
- Patients must have a histologically confirmed solid malignancy by the Laboratory of Pathology at the Clinical Center/NIH or the Laboratory of Pathology at NNMC.
- Patients must: have either relapsed following, or progressed through, standard therapy; have a current disease state for which there is no standard effective therapy; have refused standard therapy in cases where no curative option exists.
- Patients may have had any number of chemotherapeutic regimens.
- Age greater than or equal to 18 years of age.
- ECOG performance score of less than or equal to 2.
- An expected survival of greater than or equal to 3 months.
Show all 17Show fewer
- Patients must have the capacity and willingness to sign a written informed consent and demonstrate willingness to comply with an oral regimen.
- Patients must have normal organ and marrow function as defined below:
- absolute neutrophil count greater than or equal to 1,500/mL.
- platelets greater than or equal to 100,000/mL.
- total bilirubin less than 1.5 X upper limit of institutional normal.
- AST(SGOT) less than or equal to 2.5 X upper limit of institutional normal.
- ALT(SGPT) less than or equal to 2.5 X upper limit of institutional normal.
- Creatinine less than 1.5 X upper limit of institutional normal.
- Patients must agree to use non-hormonal methods of birth control, e.g., barrier methods, for the duration of the study due to possible drug interactions.
- Patients will be asked if they would consent to a biopsy before and after treatment in order to provide biologic correlates for analysis, but these will be optional, and the patients will be eligible whether they consent to do this or not.
- Patients with brain metastasis must have undergone evaluation and appropriate counseling and treatment by radiation oncology.
Who cannot join
- Pregnant or lactating women.
- Patients who have had chemotherapy or biologic agents in the last 28 days prior to entering the study.
- Any concurrent therapy with chemotherapeutic agents or biologic agents or radiation therapy.
- Patients with a myocardial infarction in the six months prior to enrollment.
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients that are on the following CYP3A4 inhibitors and cannot replace these medications with other equivalent medications for the period of the study: antiarrhythmics (amiodarone, quinidine), neuroleptics (pimozide), sedative/hypnotic agents (midazolam, triazolam), ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), HMG-CoA reductase inhibitors (lovastatin, simvastatin, atorvastatin), rifampin, rifabutin, felodipine, nifedipine, and sildenafil or St. John's wort. Patients whose baseline medication regimen includes 2 or more medications of a class carries the potential for serious side effects, and which must be changed becaused of potential interaction with nelfinavir, they must be stable on the new regimen for 7 days before enrollment.
- Patients that are on escalating doses of corticosteroids for other non-cancerous medical conditions.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Trial of Nelfinavir (Viracept) in Adults With Solid Tumors
Background:
- The PI3K/Akt/mTOR pathway is an important target in cancer because it promotes chemotherapeutic resistance and confers a poor prognosis for many types of cancers.
- Several inhibitors of the pathway are being developed as cancer therapeutics. However, the process of de novo drug development takes years, and is often curtailed due to diminished activity and/or unforeseen toxicities in clinical trials.
- One approach to expedite the development of new cancer therapies is to test drugs that are already approved for other indications.
- Our group has shown that nelfinavir, an orally available FDA-approved HIV-1 protease inhibitor used to treat HIV/AIDS, can inhibit endogenous Akt and growth factor receptor induced Akt activity in cancer cells.
- Importantly, nelfinavir demonstrates dose-dependent cytotoxicity in every cell line in the NCI 60 cell line panel at plasma concentrations attainable in human plasma, is profoundly effective in cancer cell lines that have been selected to become resistant to standard therapies, and inhibits tumor growth in-vivo.
Read more
Objectives:
- Because an MTD with nelfinavir has not been observed in prior phase I studies with HIV patients, the objectives of the Phase I design will be:
- To establish the MTD and dose limiting toxicity for this drug in patients with solid Tumors.
- To correlate nelfinavir pharmacokinetics with baseline activity of CYP3A4 as assessed by measuring midazolam clearance.
- To preliminarily explore the biological and clinical effects through a series of correlative studies involving analysis of blood and tissue across patients throughout the study.
Eligibility:
-Adults with solid tumors who are refractory to, or have relapsed after receiving, standard front-line chemotherapies are eligible.
Design:
- Patients will receive nelfinavir beginning at the FDA-approved dose for HIV patients (1250 mg po bid).
- Dose escalations will occur for 6 dose levels i.e. cohorts, or until the MTD is reached.
- Up to 45 patients are expected to be enrolled.
- Staging CT scans will be performed every two cycles.
Read the detailed description
Background:
-The PI3K/Akt/mTOR pathway is an important target in cancer because it promotes
chemotherapeutic resistance and confers a poor prognosis for many types of cancers.
- Several inhibitors of the pathway are being developed as cancer therapeutics. However, the process of de novo drug development takes years, and is often curtailed due to diminished activity and/or unforeseen toxicities in clinical trials.
- One approach to expedite the development of new cancer therapies is to test drugs that are already approved for other indications.
- Our group has shown that nelfinavir, an orally available FDA-approved HIV-1 protease inhibitor used to treat HIV/AIDS, can inhibit endogenous Akt and growth factor receptor induced Akt activity in cancer cells.
-Importantly, nelfinavir demonstrates dose-dependent cytotoxicity in every cell line in the
NCI 60 cell line panel at plasma concentrations attainable in human plasma, is profoundly
effective in cancer cell lines that have been selected to become resistant to standard therapies, and inhibits tumor growth in-vivo.
Objectives:
-Because an MTD with nelfinavir has not been observed in prior phase I studies with HIV
patients, the objectives of the Phase I design will be:
-To establish the MTD and dose limiting toxicity for this drug in patients with solid
Tumors.
-To correlate nelfinavir pharmacokinetics with baseline activity of CYP3A4 as
assessed by measuring midazolam clearance.
-To preliminarily explore the biological and clinical effects through a series of
correlative studies involving analysis of blood and tissue across patients throughout
the study.
Eligibility:
-Adults with solid tumors who are refractory to, or have relapsed after receiving, standard
front-line chemotherapies are eligible.
Design:
- Patients will receive nelfinavir beginning at the FDA-approved dose for HIV patients (1250 mg po bid).
- Dose escalations will occur for 6 dose levels i.e. cohorts, or until the MTD is reached.
- Up to 45 patients are expected to be enrolled.
- Staging CT scans will be performed every two cycles.
- Conditions
- Solid Tumors
- Being tested
- Nelfinavir, Nelfinavir Mesylate
- Keywords
- HIV Protease Inhibitor, Drug Repositioning, Akt/Mtor Inhibitor, Targeted Therapy, Off - Label Drugs, Nelfinavir, Protease Inhibitor, Solid Tumor, Phase I, Malignant Tumor
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NelfinavirDrug
Nelfinavir MesylateDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and toxicity of nelfinavir in human subjects with solid tumors and to determine the maximum tolerated dose in this group of patients.
Secondary outcomes (1)
To determine the PK of nelfinavir admin, correlate cytochrome P450 3A4 activity with nelfinavir levels and establish prelim evidence of clinical efficacy of this regimen in solid tumor malignancy patients.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2011 (estimated)
- Study start11 Dec 2006
- Primary completion9 May 2011
- Study completion9 May 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Investigators
- Arun Rajan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01445106
- Sponsor's protocol ID
- 070047
- Other IDs
- 07-C-0047
- Status last verified
- 2 Dec 2014
- First submitted
- 30 Sep 2011
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Balsara BR, Pei J, Mitsuuchi Y, Page R, Klein-Szanto A, Wang H, Unger M, Testa JR. Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions. Carcinogenesis. 2004 Nov;25(11):2053-9. doi: 10.1093/carcin/bgh226. Epub 2004 Jul 7.
PubMed 15240509Bernal-Mizrachi E, Fatrai S, Johnson JD, Ohsugi M, Otani K, Han Z, Polonsky KS, Permutt MA. Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cells. J Clin Invest. 2004 Oct;114(7):928-36. doi: 10.1172/JCI20016.
PubMed 15467831Bernal-Mizrachi E, Wen W, Stahlhut S, Welling CM, Permutt MA. Islet beta cell expression of constitutively active Akt1/PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J Clin Invest. 2001 Dec;108(11):1631-8. doi: 10.1172/JCI13785.
PubMed 11733558
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Nelfinavir (Viracept) in Adults With Solid Tumors
- ClinicalTrials.gov ID
- NCT01445106
- Acronym / sponsor ID
- 070047
- Conditions
- Solid Tumors
- Keywords
- HIV Protease Inhibitor, Drug Repositioning, Akt/Mtor Inhibitor, Targeted Therapy, Off - Label Drugs, Nelfinavir, Protease Inhibitor, Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 11 Dec 2006
- Primary completion
- 9 May 2011 (actual)
- Study completion
- 9 May 2011 (actual)
- First posted
- 3 Oct 2011 (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.
Background:
- The PI3K/Akt/mTOR pathway is an important target in cancer because it promotes chemotherapeutic resistance and confers a poor prognosis for many types of cancers.
- Several inhibitors of the pathway are being developed as cancer therapeutics. However, the process of de novo drug development takes years, and is often curtailed due to diminished activity and/or unforeseen toxicities in clinical trials.
- One approach to expedite the development of new cancer therapies is to test drugs that are already approved for other indications.
- Our group has shown that nelfinavir, an orally available FDA-approved HIV-1 protease inhibitor used to treat HIV/AIDS, can inhibit endogenous Akt and growth factor receptor induced Akt activity in cancer cells.
- Importantly, nelfinavir demonstrates dose-dependent cytotoxicity in every cell line in the NCI 60 cell line panel at plasma concentrations attainable in human plasma, is profoundly effective in cancer cell lines that have been selected to become resistant to standard therapies, and inhibits tumor growth in-vivo.
Objectives:
- Because an MTD with nelfinavir has not been observed in prior phase I studies with HIV patients, the objectives of the Phase I design will be:
- To establish the MTD and dose limiting toxicity for this drug in patients with solid Tumors.
- To correlate nelfinavir pharmacokinetics with baseline activity of CYP3A4 as assessed by measuring midazolam clearance.
- To preliminarily explore the biological and clinical effects through a series of correlative studies involving analysis of blood and tissue across patients throughout the study.
Eligibility:
-Adults with solid tumors who are refractory to, or have relapsed after receiving, standard front-line chemotherapies are eligible.
Design:
- Patients will receive nelfinavir beginning at the FDA-approved dose for HIV patients (1250 mg po bid).
- Dose escalations will occur for 6 dose levels i.e. cohorts, or until the MTD is reached.
- Up to 45 patients are expected to be enrolled.
- Staging CT scans will be performed every two cycles.
Detailed description
Background:
-The PI3K/Akt/mTOR pathway is an important target in cancer because it promotes
chemotherapeutic resistance and confers a poor prognosis for many types of cancers.
- Several inhibitors of the pathway are being developed as cancer therapeutics. However, the process of de novo drug development takes years, and is often curtailed due to diminished activity and/or unforeseen toxicities in clinical trials.
- One approach to expedite the development of new cancer therapies is to test drugs that are already approved for other indications.
- Our group has shown that nelfinavir, an orally available FDA-approved HIV-1 protease inhibitor used to treat HIV/AIDS, can inhibit endogenous Akt and growth factor receptor induced Akt activity in cancer cells.
-Importantly, nelfinavir demonstrates dose-dependent cytotoxicity in every cell line in the
NCI 60 cell line panel at plasma concentrations attainable in human plasma, is profoundly
effective in cancer cell lines that have been selected to become resistant to standard therapies, and inhibits tumor growth in-vivo.
Objectives:
-Because an MTD with nelfinavir has not been observed in prior phase I studies with HIV
patients, the objectives of the Phase I design will be:
-To establish the MTD and dose limiting toxicity for this drug in patients with solid
Tumors.
-To correlate nelfinavir pharmacokinetics with baseline activity of CYP3A4 as
assessed by measuring midazolam clearance.
-To preliminarily explore the biological and clinical effects through a series of
correlative studies involving analysis of blood and tissue across patients throughout
the study.
Eligibility:
-Adults with solid tumors who are refractory to, or have relapsed after receiving, standard
front-line chemotherapies are eligible.
Design:
- Patients will receive nelfinavir beginning at the FDA-approved dose for HIV patients (1250 mg po bid).
- Dose escalations will occur for 6 dose levels i.e. cohorts, or until the MTD is reached.
- Up to 45 patients are expected to be enrolled.
- Staging CT scans will be performed every two cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients must have a histologically confirmed solid malignancy by the Laboratory of Pathology at the Clinical Center/NIH or the Laboratory of Pathology at NNMC.
- Patients must: have either relapsed following, or progressed through, standard therapy; have a current disease state for which there is no standard effective therapy; have refused standard therapy in cases where no curative option exists.
- Patients may have had any number of chemotherapeutic regimens.
- Age greater than or equal to 18 years of age.
- ECOG performance score of less than or equal to 2.
Key exclusion criteria (7 listed)
- Pregnant or lactating women.
- Patients who have had chemotherapy or biologic agents in the last 28 days prior to entering the study.
- Any concurrent therapy with chemotherapeutic agents or biologic agents or radiation therapy.
- Patients with a myocardial infarction in the six months prior to enrollment.
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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 |
|---|---|---|
| Nelfinavir | Drug | – |
| Nelfinavir Mesylate | Drug | – |
Primary outcome
To determine the safety and toxicity of nelfinavir in human subjects with solid tumors and to determine the maximum tolerated dose in this group of patients.
1 secondary outcome
To determine the PK of nelfinavir admin, correlate cytochrome P450 3A4 activity with nelfinavir levels and establish prelim evidence of clinical efficacy of this regimen in solid tumor malignancy patients.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 15240509Balsara BR, Pei J, Mitsuuchi Y, Page R, Klein-Szanto A, Wang H, Unger M, Testa JR. Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions. Carcinogenesis. 2004 Nov;25(11):2053-9. doi: 10.1093/carcin/bgh226. Epub 2004 Jul 7.
- Background: PubMed 15467831Bernal-Mizrachi E, Fatrai S, Johnson JD, Ohsugi M, Otani K, Han Z, Polonsky KS, Permutt MA. Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cells. J Clin Invest. 2004 Oct;114(7):928-36. doi: 10.1172/JCI20016.
- Background: PubMed 11733558Bernal-Mizrachi E, Wen W, Stahlhut S, Welling CM, Permutt MA. Islet beta cell expression of constitutively active Akt1/PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J Clin Invest. 2001 Dec;108(11):1631-8. doi: 10.1172/JCI13785.
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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.
Arun Rajan, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nelfinavir and Nelfinavir Mesylate in people with Solid Tumors, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 7 exclusion criteria. 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: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the safety and toxicity of nelfinavir in human subjects with solid tumors and to determine the maximum tolerated dose in this group of patients.. 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 NCT01445106, which also lists 3 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 17 Dec 2019.