Non-small Cell Lung CancerEarly Phase 1NCT02357836
Neoadjuvant Itraconazole in Non-small Cell Lung Cancer
A Early Phase 1 study testing Itraconazole in people with Non-small Cell Lung Cancer, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
The purpose of this study is to determine the pharmacodynamics effects of itraconazole in early-stage non-small cell lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Itraconazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to Jul 2018
- Phase
- Early Phase 1
- 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
- Histologically or cytologically proven NSCLC planned for surgical resection. All NSCLC histologic subtypes are eligible. Alternatively, patients in whom a diagnosis of NSCLC is highly suspected based on history and imaging studies and who are, therefore, scheduled for diagnostic biopsy and/or surgical resection will also be eligible for screening, enrollment, and study treatment if they meet all additional eligibility criteria. In the event that biopsies do not confirm NSCLC, such patients will be removed from study but monitored for any adverse events resulting from study participation.
- No prior therapy but planned for surgical resection
- Age ≥ 18 years.
- ECOG (Eastern Cooperative Oncology Group) 0-2 performance status
- Adequate organ function as defined below:
- total bilirubin within normal institutional limits
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- AST (Aspartate Aminotransferase) (SGOT)/ALT (Alanine Aminotransferase) (SPGT) ≤ 2.5 X institutional upper limit of normal
- creatinine ≤ 2 X institutional upper limit of normal
- 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, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- 6.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Ability to understand and willingness to sign a written informed consent.
Who cannot join
- Subjects may not be receiving any investigational agents that would confound interpretation of study pharmacodynamic endpoints.
- History of allergic reactions attributed to itraconazole or to compounds of similar chemical or biologic composition to itraconazole.
- Uncontrolled, concurrent medical illness.
- Active hepatitis or symptomatic liver disease.
- History of or current evidence of uncontrolled cardiac ventricular dysfunction (congestive heart failure) or NYHA (New York Heart Association) Class III or IV heart failure.
- Current use of medications significantly affecting metabolism of itraconazole (certain anti-convulsants, corticosteroids). See 3.5 Drug Interactions in protocol.
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- Current evidence of hyperthyroidism (which would increase metabolism of itraconazole).
- Pregnant or lactating female or any female trying to get pregnant.
- Claustrophobia that would interfere with MRI studies anticipated to last 45-50 minutes.
- Metal implants deemed at risk for migration during MRI studies.
- CrCl (Creatinine clearance) < 45 mL/min (increased risk of nephrogenic systemic fibrosis [NSF] from MRI Gadolinium contrast).
- Known allergy to MRI contrast.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 0 Pharmacodynamic Study of the Effects of Itraconazole on Tumor Angiogenesis and the Hedgehog Pathway in Early-stage Non-small Cell Lung Cancer
The purpose of this study is to determine the pharmacodynamics effects of itraconazole in early-stage non-small cell lung cancer.
Read the detailed description
This is a phase 0 clinical trial. While clinical data including safety will be recorded, the principal outcomes are pharmacodynamic endpoints. Specifically, the investigators seek to identify: (1) effects of itraconazole on tumor angiogenesis, (2) effects of itraconazole on the Hh pathway, (3) biomarker predictors of these effects, (4) the correlation between itraconazole pharmacokinetics and these effects, (5) the correlation between different biomarkers.
Up to 15 eligible patients with previously diagnosed or suspected NSCLC planned for resection will undergo a study-specific core needle biopsy, imaging (dynamic contrast enhanced [DCE]-, diffusion weighted imaging [DWI]-, and arterial spin labeling [ASL] magnetic resonance imaging [MRI]), skin punch biopsy, and collection of peripheral blood. Subjects will then receive itraconazole 600 mg PO daily for 7-10 days, following which they will undergo repeat imaging, skin biopsy, and blood collection. Subsequently they will undergo surgical resection. Due to the safety profile of itraconazole when used as an antifungal agent , all histologic subtypes of NSCLC will be eligible for the trial. The itraconazole dose of 600 mg, higher than an anti-angiogenic dose, has been shown to inhibit the Hedgehog (Hh) pathway.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Itraconazole
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ItraconazoleDrug
Once on study, itraconazole will be taken twice daily for a total of 10-14 days. After being on itraconazole for 7-10 days, "Post-treatment" assessments will include a skin biopsy, blood draw for the PK (pharmacokinetics) analyses and the cytokine panel, and also MRI evaluations (anticipated to last 45-50 minutes). Toxicity assessments and laboratory checks will also be conducted during that time. Following these assessments, itraconazole will be continued until the day of surgery. At the time of surgical resection, a tissue sample (with adjacent normal tissue as per standard resection technique) will be obtained to complete the analysis. Following resection, subjects will be followed per standard post-operative procedure.
| Study group | Role | What they receive |
|---|---|---|
| Itraconazole | Other | 600 mg twice daily for 10-14 days Receives: Drug: Itraconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Tumor Tissue Microvessel Density [MVD] From Baseline
Images of DAPI (4',6-Diamidino-2-Phenylindole) , CD31 (cluster of differentiation 31 ), and CD34 (cluster of differentiation 34) were taken from the same field of view and then merged.
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Secondary outcomes (15)
Change in HIF1α From Baseline
A commercially available kit will be used to measure HIF1α levels.
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in VEGFR2 From Baseline
A commercially available kit will be used to measure VEGFR2 levels.
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in Phospho-VEGFR2 From Baseline
A commercially available kit will be used to measure Phospho-VEGFR2 levels.
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
The following plasma cytokines were measured using a commercially available kit.
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Mean Percent Change in Angiogenic Cytokines From Baseline
A commercially available kit will be used to measure Angiogenic Cytokines levels.
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Changes in Perfusion (Ktrans)
DCE (dynamic contrast enhanced ) MRI is an established technology to assess microvessel density (MVD) and tumor capillary permeability.
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Number of Participants With Tumor SMO (Smoothened) Gene Mutations, GLI2 and CCND1 Copy Number, PI3K-mTOR Pathway Activation
phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (PI3K-mTOR pathway )
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in Tumor Tissue GLI1, SHH and PTCH1 Levels From Baseline
This can be measured by analyzing frozen-treated tumor tissue for GLI1 (glioma-associated oncogene ) and PTCH1(patched-1) mRNA (Messenger Ribonucleic Acid) by qPCR.
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in Skin Biopsy GLI1 Levels From Baseline
We analyzed serial skin biopsies for GLI1 mRNA by qPCR (quantitative polymerase chain reaction).
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in Skin Biopsy SHH Levels From Baseline
We analyzed serial skin biopsies for SHH (Sonic Hedgehog )levels mRNA by qPCR.
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in Skin Biopsy PTCH1 Levels From Baseline
We analyzed serial skin biopsies for PTCH1 mRNA by qPCR.
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Number of Participants With Tumor Cell Proliferation/Apoptosis
Tumor proliferation and apoptosis will be assessed by tumor Ki67 and cleaved caspase 3 levels
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Itraconazole Levels in Post-treatment Serum
Itraconazole levels assessed by post-treatment serum
Measured: Post Treatment (after 7-10 days of itraconazole bid)
Itraconazole Levels in Tumor Tissue
Itraconazole levels assessed by tumor tissue
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Itraconazole Levels in Skin Biopsy
Itraconazole levels assessed by skin biopsy
Measured: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2015 (estimated)
- Study startJun 2015
- Primary completionJul 2018
- Study completionJul 2018
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.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, David E Gerber, University of Texas Southwestern Medical Center
- Investigators
- Lorraine Pelosof, M.D., Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02357836
- Sponsor's protocol ID
- STU 122014-038
- Status last verified
- Apr 2021
- First submitted
- 15 Jan 2015
- Last updated
- 3 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 0 Pharmacodynamic Study of the Effects of Itraconazole on Tumor Angiogenesis and the Hedgehog Pathway in Early-stage Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02357836
- Acronym / sponsor ID
- STU 122014-038
- Conditions
- Non-small Cell Lung Cancer
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- Jun 2015 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 6 Feb 2015 (estimated)
- Results
- Posted 3 May 2021
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 determine the pharmacodynamics effects of itraconazole in early-stage non-small cell lung cancer.
Detailed description
This is a phase 0 clinical trial. While clinical data including safety will be recorded, the principal outcomes are pharmacodynamic endpoints. Specifically, the investigators seek to identify: (1) effects of itraconazole on tumor angiogenesis, (2) effects of itraconazole on the Hh pathway, (3) biomarker predictors of these effects, (4) the correlation between itraconazole pharmacokinetics and these effects, (5) the correlation between different biomarkers.
Up to 15 eligible patients with previously diagnosed or suspected NSCLC planned for resection will undergo a study-specific core needle biopsy, imaging (dynamic contrast enhanced [DCE]-, diffusion weighted imaging [DWI]-, and arterial spin labeling [ASL] magnetic resonance imaging [MRI]), skin punch biopsy, and collection of peripheral blood. Subjects will then receive itraconazole 600 mg PO daily for 7-10 days, following which they will undergo repeat imaging, skin biopsy, and blood collection. Subsequently they will undergo surgical resection. Due to the safety profile of itraconazole when used as an antifungal agent , all histologic subtypes of NSCLC will be eligible for the trial. The itraconazole dose of 600 mg, higher than an anti-angiogenic dose, has been shown to inhibit the Hedgehog (Hh) pathway.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Itraconazole | Other | Drug: Itraconazole600 mg twice daily for 10-14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically or cytologically proven NSCLC planned for surgical resection. All NSCLC histologic subtypes are eligible. Alternatively, patients in whom a diagnosis of NSCLC is highly suspected based on history and imaging studies and who are, therefore, scheduled for diagnostic biopsy and/or surgical resection will also be eligible for screening, enrollment, and study treatment if they meet all additional eligibility criteria. In the event that biopsies do not confirm NSCLC, such patients will be removed from study but monitored for any adverse events resulting from study participation.
- No prior therapy but planned for surgical resection
- Age ≥ 18 years.
- ECOG (Eastern Cooperative Oncology Group) 0-2 performance status
- Adequate organ function as defined below:
Key exclusion criteria (12 listed)
- Subjects may not be receiving any investigational agents that would confound interpretation of study pharmacodynamic endpoints.
- History of allergic reactions attributed to itraconazole or to compounds of similar chemical or biologic composition to itraconazole.
- Uncontrolled, concurrent medical illness.
- Active hepatitis or symptomatic liver disease.
- History of or current evidence of uncontrolled cardiac ventricular dysfunction (congestive heart failure) or NYHA (New York Heart Association) Class III or IV heart failure.
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 |
|---|---|---|
| ItraconazoleOnce on study, itraconazole will be taken twice daily for a total of 10-14 days. After being on itraconazole for 7-10 days, "Post-treatment" assessments will include a skin biopsy, blood draw for the PK (pharmacokinetics) analyses and the cytokine panel, and also MRI evaluations (anticipated to last 45-50 minutes). Toxicity assessments and laboratory checks will also be conducted during that time. Following these assessments, itraconazole will be continued until the day of surgery. At the time of surgical resection, a tissue sample (with adjacent normal tissue as per standard resection technique) will be obtained to complete the analysis. Following resection, subjects will be followed per standard post-operative procedure. | Drug | Itraconazole |
Primary outcome
Changes in Tumor Tissue Microvessel Density [MVD] From Baseline
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Images of DAPI (4',6-Diamidino-2-Phenylindole) , CD31 (cluster of differentiation 31 ), and CD34 (cluster of differentiation 34) were taken from the same field of view and then merged.
15 secondary outcomes
Change in HIF1α From Baseline
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in VEGFR2 From Baseline
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in Phospho-VEGFR2 From Baseline
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Mean Percent Change in Angiogenic Cytokines From Baseline
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Changes in Perfusion (Ktrans)
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Number of Participants With Tumor SMO (Smoothened) Gene Mutations, GLI2 and CCND1 Copy Number, PI3K-mTOR Pathway Activation
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in Tumor Tissue GLI1, SHH and PTCH1 Levels From Baseline
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in Skin Biopsy GLI1 Levels From Baseline
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in Skin Biopsy SHH Levels From Baseline
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Change in Skin Biopsy PTCH1 Levels From Baseline
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Number of Participants With Tumor Cell Proliferation/Apoptosis
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Itraconazole Levels in Post-treatment Serum
Time frame: Post Treatment (after 7-10 days of itraconazole bid)
Itraconazole Levels in Tumor Tissue
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Itraconazole Levels in Skin Biopsy
Time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Lorraine Pelosof, M.D. principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Itraconazole in people with Non-small Cell Lung Cancer, run by University of Texas Southwestern Medical Center 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 13 inclusion and 12 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 3 May 2021. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 3 May 2021). 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?
Changes in Tumor Tissue Microvessel Density [MVD] From Baseline (time frame: Baseline and Post Treatment (after 7-10 days of itraconazole bid)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 May 2021.