Trial Outcomes & Findings for Neoadjuvant Itraconazole in Non-small Cell Lung Cancer (NCT NCT02357836)
NCT ID: NCT02357836
Last Updated: 2021-05-03
Results Overview
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.
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
13 participants
Primary outcome timeframe
Baseline and Post Treatment (after 7-10 days of itraconazole bid)
Results posted on
2021-05-03
Participant Flow
Participant milestones
| Measure |
Itraconazole
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Overall Study
STARTED
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13
|
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Overall Study
COMPLETED
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13
|
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Neoadjuvant Itraconazole in Non-small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Itraconazole
n=13 Participants
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Age, Continuous
|
64 years
STANDARD_DEVIATION 0.05 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
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Region of Enrollment
United States
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13 participants
n=5 Participants
|
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Histology
Adenocarcinoma
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9 Participants
n=5 Participants
|
|
Histology
Squamous Cell
|
2 Participants
n=5 Participants
|
|
Histology
Other
|
2 Participants
n=5 Participants
|
|
Smoking History
Former
|
10 Participants
n=5 Participants
|
|
Smoking History
Never
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Itraconazole
n=13 Participants
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Changes in Tumor Tissue Microvessel Density [MVD] From Baseline
|
0.005 Percent area fraction
Standard Deviation 0.045
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SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: We did not collect this data as we did not perform this assay.
A commercially available kit will be used to measure HIF1α levels.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: We did not collect this data as we did not perform this assay.
A commercially available kit will be used to measure VEGFR2 levels.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: We did not collect this data as we did not perform this assay.
A commercially available kit will be used to measure Phospho-VEGFR2 levels.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: The 2 missing cases not included in this analysis here were due to inability to collect the follow-up sample.
The following plasma cytokines were measured using a commercially available kit.
Outcome measures
| Measure |
Itraconazole
n=11 Participants
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-1b
|
-14.4159 Percent change
Standard Error 117.2143
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-1ra
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-16.9648 Percent change
Standard Error 72.1061
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-2
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-21.5999 Percent change
Standard Error 81.7471
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-4
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-5.0114 Percent change
Standard Error 36.6851
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-5
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-13.7573 Percent change
Standard Error 71.6122
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-6
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-62.5420 Percent change
Standard Error 103.4791
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-7
|
-21.9919 Percent change
Standard Error 64.4562
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-9
|
-0.9209 Percent change
Standard Error 56.3665
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-10
|
2.9705 Percent change
Standard Error 118.2381
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-12
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-30.0689 Percent change
Standard Error 99.9174
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-13
|
-16.1310 Percent change
Standard Error 75.8152
|
|
Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-15
|
-27.7823 Percent change
Standard Error 92.4703
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IL-17
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-24.3512 Percent change
Standard Error 82.8199
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IP-10
|
-16.7481 Percent change
Standard Error 60.9495
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
MCP-1
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-11.3317 Percent change
Standard Error 34.8165
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
MIP-1a
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-14.7291 Percent change
Standard Error 76.0138
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
MIP-1b
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0.0767 Percent change
Standard Error 57.2234
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
RANTES
|
5.1468 Percent change
Standard Error 128.1372
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
TNF-a
|
-18.0238 Percent change
Standard Error 44.3590
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
IFN-g
|
-39.7280 Percent change
Standard Error 62.7207
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
Eotaxin
|
2.8770 Percent change
Standard Error 31.7644
|
|
Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
G-CSF
|
-4.4567 Percent change
Standard Error 30.0457
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Mean Percent Change in Other Plasma Cytokine From Baseline to Post-Treatment
GM-CSF
|
-45.6701 Percent change
Standard Error 60.2840
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SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: The 2 missing cases not included in this analysis here were due to inability to collect the follow-up sample.
A commercially available kit will be used to measure Angiogenic Cytokines levels.
Outcome measures
| Measure |
Itraconazole
n=11 Participants
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Mean Percent Change in Angiogenic Cytokines From Baseline
IL-8
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-4.5391 Percent change
Standard Error 124.2834
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Mean Percent Change in Angiogenic Cytokines From Baseline
PDGF-bb
|
7.7116 Percent change
Standard Error 209.4990
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Mean Percent Change in Angiogenic Cytokines From Baseline
VEGF
|
-13.5786 Percent change
Standard Error 47.4821
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Mean Percent Change in Angiogenic Cytokines From Baseline
FGF-b
|
-35.5341 Percent change
Standard Error 65.0768
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SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: Reasons that enrolled patients did not complete paired research MRI scans included presence of metal implants, inadequate renal function, and patient preference
DCE (dynamic contrast enhanced ) MRI is an established technology to assess microvessel density (MVD) and tumor capillary permeability.
Outcome measures
| Measure |
Itraconazole
n=9 Participants
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Changes in Perfusion (Ktrans)
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0.008 min-1
Standard Deviation 0.072
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SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: This was initially planned and did not collect data for this and did not assess.
phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (PI3K-mTOR pathway )
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: The lab tests were not feasible with tumor tissues as they were not enough to conduct these tests.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: Participant with missing data were excluded from the analysis
We analyzed serial skin biopsies for GLI1 mRNA by qPCR (quantitative polymerase chain reaction).
Outcome measures
| Measure |
Itraconazole
n=12 Participants
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Change in Skin Biopsy GLI1 Levels From Baseline
|
0.27347 relative units
Standard Deviation 0.54713
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SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: SHH levels were not measured.
We analyzed serial skin biopsies for SHH (Sonic Hedgehog )levels mRNA by qPCR.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: Participant with missing data were excluded from the analysis
We analyzed serial skin biopsies for PTCH1 mRNA by qPCR.
Outcome measures
| Measure |
Itraconazole
n=12 Participants
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Change in Skin Biopsy PTCH1 Levels From Baseline
|
0.03164 relative units
Standard Deviation 0.22360
|
SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: This was not feasible with the available tissue samples and hence data not collected.
Tumor proliferation and apoptosis will be assessed by tumor Ki67 and cleaved caspase 3 levels
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Treatment (after 7-10 days of itraconazole bid)Population: The 2 missing cases not included in this analysis here were due to inability to collect the follow-up sample.
Itraconazole levels assessed by post-treatment serum
Outcome measures
| Measure |
Itraconazole
n=11 Participants
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Itraconazole Levels in Post-treatment Serum
|
1264 ng/mL
Standard Deviation 688
|
SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: The 4 missing cases not included in this analysis here were due to inability to collect the follow-up sample.
Itraconazole levels assessed by tumor tissue
Outcome measures
| Measure |
Itraconazole
n=9 Participants
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Itraconazole Levels in Tumor Tissue
|
2585 ng/g
Standard Deviation 1986
|
SECONDARY outcome
Timeframe: Baseline and Post Treatment (after 7-10 days of itraconazole bid)Population: We have not measured itraconazole level in skin biopsy.
Itraconazole levels assessed by skin biopsy
Outcome measures
Outcome data not reported
Adverse Events
Itraconazole
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Itraconazole
n=13 participants at risk
600 mg twice daily for 10-14 days
Itraconazole: 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 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.
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|---|---|
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Gastrointestinal disorders
Nausea
|
15.4%
2/13 • 10 days
|
|
Gastrointestinal disorders
Heartburn
|
7.7%
1/13 • 10 days
|
|
General disorders
Non-Cardiac chest pain
|
7.7%
1/13 • 10 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place