Carcinoma, Adenoid CysticPhase 2NCT01065844
Nelfinavir in Recurrent Adenoid Cystic Cancer of the Head and Neck
A Phase 2 study testing Nelfinavir in people with Carcinoma, Adenoid Cystic and Head and Neck Neoplasms, run by University of Iowa at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the FDA-approved drug nelfinavir (NFV) as an oncologic agent for adenoid cystic cancers of the head and neck. Specifically, subjects will be asked to take 1250 mg twice daily and follow-up with their medical oncologist as clinically indicated while taking this medication. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Adenoid Cystic, Head and Neck Neoplasms
- What is being tested?
- Nelfinavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Nov 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histological diagnosis of adenoid cystic carcinoma.
- Cancer should be staged recurrent or end-stage with/without metastases who have failed all other therapy.
- Age ≥ 18 years
- ECOG performance status 0-2 (Karnofsky ≥ 50%, see Appendix A).
- Patients must have normal organ and marrow function as defined below:
- leukocytes ≥ 3,000/mm3
Show all 15Show fewer
- absolute neutrophil count ≥ 1,500/mm3
- platelets ≥ 100,000/mm3
- total bilirubin < 1.5 mg/dl OR a stable or a decreasing bilirubin in patients who have undergone placement of an intrabiliary stent
- AST(SGOT) ≤ 2.5 X institutional upper limit of normal
- ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
- creatinine < 1.5 X institutional upper limit of normal OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
- No known HIV infection. Since NFV is used in HIV patients, we do not want to interfere with the therapy the patient may already be on.
- Not pregnant. The effects of NFV on the developing human fetus have been studied in HIV positive women (21). We do not, however, know the risks along with radiation. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to NFV.
- Uncontrolled diabetes.
- Hemophilia A \& B as increased bleeding during protease inhibitor therapy has been reported (22).
- Patients may not be receiving any other investigational agents. concomitant medications counterindicated for use with nelfinavir
- Pregnant or lactating women: The effects of NFV on the developing human fetus have been studied in HIV positive women (21). In addition, the chemotherapy will be deleterious to the fetus.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with NFV.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
About this study
Official title: A Phase II Trial of the HIV Protease Inhibitor Nelfinavir in Patients With Recurrent Symptomatic Adenoid Cystic Cancers of the Head and Neck
The purpose of this study is to evaluate the FDA-approved drug nelfinavir (NFV) as an oncologic agent for adenoid cystic cancers of the head and neck.
Specifically, subjects will be asked to take 1250 mg twice daily and follow-up with their medical oncologist as clinically indicated while taking this medication.
Read more
Subjects would be evaluated for quality of life issues utilizing the EORTC QLQ-C30 2-page questionnaire.
Subjects would also be evaluated clinically by the oncologist to determine if the NFV was having an anti-neoplastic effect.
The study remains unfunded. Therefore, potential subjects must be willing to provide self-travel to study site. This study requires a screening visit, initial study visit, and monthly follow-up. Subjects are not reimbursed for time, travel, or physician costs.
Read the detailed description
The hypothesis of this study is that nelfinavir, by inhibiting the Akt and MAPK pathways, can inhibit adenoid cystic carcinoid growth. These cancers are heavily dependent on these signalling pathways.
Adenoid cystic carcinomas (ACC) are rare and account for about 1% of all head and neck cancers. They stem from salivary glands and are known for their tendency to spread along nerve sheaths (perineural spread). ACC is known for its prolonged clinical course, multiple recurrence and the delayed onset of distant metastases. The median/mean age at presentation is 47-56. Although 5 year disease free survivals (DFS) are 65-70%, the 15 year DFS drops to 30-40%. If followed long enough, 35% of patients will eventually develop metastatic disease.
The most common treatment of ACC is surgery followed by post-operative radiotherapy. When ACC recurs, management options are often limited both by the morbidity and low efficacy of re-irradiation and repeated surgical resection. Reported response rates to chemotherapy are low and when it occurs, the duration of the response is short lived.
In an effort to explore possible targeted therapies for patients with recurrent ACC, Dr. Gupta's lab examined the activation of 3 signaling proteins (EGFR, Akt, and MAPK) in 9 different paraffinized tissue blocks. Initial indications from in vitro studies demonstrates NFV is tumoricidal at clinically achievable concentrations. To explore the clinical benefit of this FDA-approved medication, we seek to implement its off label use in patients who have failed all other therapies and have no other therapeutic options left.
- Conditions
- Carcinoma, Adenoid Cystic, Head and Neck Neoplasms
- Being tested
- Nelfinavir
- Keywords
- Nelfinavir
- Medical subject headings
- Carcinoma, Adenoid Cystic, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NelfinavirDrug
1250 mg Nelfinavir twice daily Monday - Sunday
| Study group | Role | What they receive |
|---|---|---|
| Nelfinavir | Experimental | 1250 mg Nelfinavir twice daily Monday-Sunday Receives: Drug: Nelfinavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Progression
Tumor progression as defined by RECIST version v1.1 criteria with ordinal measurements of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).
Measured: Every 1 to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2010 (estimated)
- Study startOct 2009
- Primary completionMay 2015
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Adenoid CysticStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 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, John M. Buatti, University of Iowa
- Investigators
- John M. Buatti, M.D., Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01065844
- Sponsor's protocol ID
- 200905704
- Status last verified
- Sep 2019
- First submitted
- 8 Feb 2010
- Last updated
- 9 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gupta AK, Wilke WW, Taylor EN, Bodeker KL, Hoffman HT, Milhem MM, Buatti JM, Robinson RA. Signaling pathways in adenoid cystic cancers: implications for treatment. Cancer Biol Ther. 2009 Oct;8(20):1947-51. doi: 10.4161/cbt.8.20.9596. Epub 2009 Oct 22.
PubMed 19729990Hoover AC, Milhem MM, Anderson CM, Sun W, Smith BJ, Hoffman HT, Buatti JM. Efficacy of nelfinavir as monotherapy in refractory adenoid cystic carcinoma: Results of a phase II clinical trial. Head Neck. 2015 May;37(5):722-6. doi: 10.1002/hed.23664. Epub 2014 Jun 18.
PubMed 24596143
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of the HIV Protease Inhibitor Nelfinavir in Patients With Recurrent Symptomatic Adenoid Cystic Cancers of the Head and Neck
- ClinicalTrials.gov ID
- NCT01065844
- Acronym / sponsor ID
- 200905704
- Conditions
- Carcinoma, Adenoid Cystic, Head and Neck Neoplasms
- Keywords
- Nelfinavir
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- Holden Comprehensive Cancer Center
- Study start
- Oct 2009 (actual)
- Primary completion
- May 2015 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 9 Feb 2010 (estimated)
- Results
- Posted 19 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the FDA-approved drug nelfinavir (NFV) as an oncologic agent for adenoid cystic cancers of the head and neck.
Specifically, subjects will be asked to take 1250 mg twice daily and follow-up with their medical oncologist as clinically indicated while taking this medication.
Subjects would be evaluated for quality of life issues utilizing the EORTC QLQ-C30 2-page questionnaire.
Subjects would also be evaluated clinically by the oncologist to determine if the NFV was having an anti-neoplastic effect.
The study remains unfunded. Therefore, potential subjects must be willing to provide self-travel to study site. This study requires a screening visit, initial study visit, and monthly follow-up. Subjects are not reimbursed for time, travel, or physician costs.
Detailed description
The hypothesis of this study is that nelfinavir, by inhibiting the Akt and MAPK pathways, can inhibit adenoid cystic carcinoid growth. These cancers are heavily dependent on these signalling pathways.
Adenoid cystic carcinomas (ACC) are rare and account for about 1% of all head and neck cancers. They stem from salivary glands and are known for their tendency to spread along nerve sheaths (perineural spread). ACC is known for its prolonged clinical course, multiple recurrence and the delayed onset of distant metastases. The median/mean age at presentation is 47-56. Although 5 year disease free survivals (DFS) are 65-70%, the 15 year DFS drops to 30-40%. If followed long enough, 35% of patients will eventually develop metastatic disease.
The most common treatment of ACC is surgery followed by post-operative radiotherapy. When ACC recurs, management options are often limited both by the morbidity and low efficacy of re-irradiation and repeated surgical resection. Reported response rates to chemotherapy are low and when it occurs, the duration of the response is short lived.
In an effort to explore possible targeted therapies for patients with recurrent ACC, Dr. Gupta's lab examined the activation of 3 signaling proteins (EGFR, Akt, and MAPK) in 9 different paraffinized tissue blocks. Initial indications from in vitro studies demonstrates NFV is tumoricidal at clinically achievable concentrations. To explore the clinical benefit of this FDA-approved medication, we seek to implement its off label use in patients who have failed all other therapies and have no other therapeutic options left.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nelfinavir | Experimental | Drug: Nelfinavir1250 mg Nelfinavir twice daily Monday-Sunday |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histological diagnosis of adenoid cystic carcinoma.
- Cancer should be staged recurrent or end-stage with/without metastases who have failed all other therapy.
- Age ≥ 18 years
- ECOG performance status 0-2 (Karnofsky ≥ 50%, see Appendix A).
- Patients must have normal organ and marrow function as defined below:
Key exclusion criteria (6 listed)
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to NFV.
- Uncontrolled diabetes.
- Hemophilia A \& B as increased bleeding during protease inhibitor therapy has been reported (22).
- Patients may not be receiving any other investigational agents. concomitant medications counterindicated for use with nelfinavir
- Pregnant or lactating women: The effects of NFV on the developing human fetus have been studied in HIV positive women (21). In addition, the chemotherapy will be deleterious to the fetus.
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 |
|---|---|---|
| Nelfinavir1250 mg Nelfinavir twice daily Monday - Sunday | Drug | Nelfinavir |
Primary outcome
Tumor Progression
Time frame: Every 1 to 3 months
Tumor progression as defined by RECIST version v1.1 criteria with ordinal measurements of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19729990Gupta AK, Wilke WW, Taylor EN, Bodeker KL, Hoffman HT, Milhem MM, Buatti JM, Robinson RA. Signaling pathways in adenoid cystic cancers: implications for treatment. Cancer Biol Ther. 2009 Oct;8(20):1947-51. doi: 10.4161/cbt.8.20.9596. Epub 2009 Oct 22.
- Results publication: PubMed 24596143Hoover AC, Milhem MM, Anderson CM, Sun W, Smith BJ, Hoffman HT, Buatti JM. Efficacy of nelfinavir as monotherapy in refractory adenoid cystic carcinoma: Results of a phase II clinical trial. Head Neck. 2015 May;37(5):722-6. doi: 10.1002/hed.23664. Epub 2014 Jun 18.
- Individual participant dataSharing planned: No
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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.
John M. Buatti, M.D. principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nelfinavir in people with Carcinoma, Adenoid Cystic and Head and Neck Neoplasms, run by University of Iowa 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 15 inclusion and 6 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 9 Oct 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Tumor Progression (time frame: Every 1 to 3 months). 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 NCT01065844, which also lists 2 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 9 Oct 2019.