Lung CancerPhase 2NCT03664115
Itraconazole in Non Small Cell Lung Cancer
A Phase 2 study testing Itraconazole 200 mg and Chemotherapy in people with Lung Cancer, run by Ain Shams University at 1 site in Egypt.
Trial summary
Circulating levels of angiogenic factors have been correlated with aggressive tumor growth, prediction of metastasis and prognosis in a wide range of solid tumors, including non-small cell lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Itraconazole 200 mg and Chemotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteEgypt
- Study dates
- 2 Jul 2018to 2 Dec 2020
- Phase
- Phase 2
- 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
- Stage IV NSCLC patients who have not received chemotherapy for metastatic disease management yet or inoperable locally recurrent Stage III NSCLC after concurrent chemoradiotherapy.
- ECOG 0-2.
- Age >18 years.
- Adequate bone marrow reserve (white blood cells [WBC] ≥ 3.5 × 109 /L, neutrophils ≥ 1.5 × 109 /L, platelets ≥ 100 × 109 /L, and hemoglobin ≥ 9.0 gm/dL).
Who cannot join
- Inadequate liver function (bilirubin > 1.5 times upper normal limit [ULN] and alanine transaminase [ALT] or aspartate transaminase [AST] > 3.0 ULN or up to 5.0 UNL in the presence of hepatic metastases).
- Inadequate renal function (creatinine > 1.25 times ULN, creatinine clearance < 50mL/min).
- Serious comorbid systemic disorder incompatible with the study.
- Presence of other primary malignancy.
- Patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF.
- Patients with hypersensitivity to Itraconazole.
- Patients receiving any Cytochrome P450 (CYP 3A4) inhibitor as clarithromycin, diltiazem, verapamil, quinidine ….etc.
- Pregnant female patients.
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
oncology department Ain shams university
Cairo, 11591
Amr sh Tawfik, MD
Asmaa WH Mohamed, Master, 01003538597, drasmaa_wahid@hotmail.com
About this study
Official title: The Effect of Itraconazole on the Clinical Outcomes of Patients With Advanced Non Small Cell Lung Cancer Receiving Platinum Based Chemotherapy
Circulating levels of angiogenic factors have been correlated with aggressive tumor growth, prediction of metastasis and prognosis in a wide range of solid tumors, including non-small cell lung cancer.
Food and Drug Administration (FDA) approved Itraconazole as an anti-angiogenic agent including both Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), and inhibited phosphorylation of the primary angiogenic receptors for these factors in 2007 and also known as an inhibitor of Hedgehog signalling, AKT (protein kinase B)/mechanistic target of rapamycin (mTOR) signaling adding its induction of autophagic cell death function based on cellular and laboratory studies, and allowed its use in phase II trials in prostate, lung and skin cancer.
Read more
Itraconazole also interferes directly with mitochondrial Adenosine triphosphate (ATP) production, leading to the activation of the adenosine monophosphate (AMP) -activated protein kinase pathway and subsequent inhibition of mTOR pathway (Head et al., 2015).
Testing Itraconazole on experimental settings was associated also with tumor hypoxia, as proved by induction of tumor-specific expression of Hypoxia-inducible factor 1-alpha (HIF1α), as well as decreased tumor micro-vessel load
Read the detailed description
Lung cancer is the leading cause of cancer death in the United States
The American Cancer Society estimates lung cancer incidence in the United States for 2018 to be about 234,030 and about 154,050 deaths.
In 2012, GLOBOCAN estimated that 1.8 million people were diagnosed with lung cancer, accounting for about 13% of total cancer diagnoses.
Lung cancer death rates declined 45% from 1990 to 2015 among men and 19% from 2002 to 2015 among women. From 2005 to 2014, the rate of new lung cancer cases dropped by 2.5% per year in men and 1.2% per year in women, These differences reflect historical patterns in tobacco use, where women began smoking in large numbers many years later than men, and were slower to quit .
World Health Organization (WHO) divides lung cancer into 2 major classes based on its biology, therapy, and prognosis: non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
The NSCLC subtype accounts for 87% of lung cancer cases with its most common types to be adenocarcinomas where it is approximately 40% of lung cancers.
Different factors like age, Performance state, co-morbidities, histology, molecular pathology and last but not least; the patient's preferences should be taken into account along the treatment strategy after a multidisciplinary tumor board discussion, to allow adequate and careful evaluation of the available data to reach the most appropriate management plan and treatment modality for each patient individually (Ung et al., 2016).
Platinum doublets Chemotherapy should be considered in all stage IV and inoperable stage III NSCLC patients with epidermal growth factor receptor (EGFR) and Anaplastic lymphoma kinase (ALK) negative disease, without major comorbidities and Performance state 0-2.
Circulating levels of angiogenic factors have been correlated with aggressive tumor growth, prediction of metastasis and prognosis in a wide range of solid tumors, including non-small cell lung cancer.
Food and Drug Administration (FDA) approved Itraconazole as an anti-angiogenic agent including both Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), and inhibited phosphorylation of the primary angiogenic receptors for these factors in 2007 and also known as an inhibitor of Hedgehog signalling, AKT (protein kinase B)/mechanistic target of rapamycin (mTOR) signaling adding its induction of autophagic cell death function based on cellular and laboratory studies, and allowed its use in phase II trials in prostate, lung and skin cancer.
Itraconazole was proved to be among one of the most potent and selective inhibitors of endothelial cell proliferation.
Itraconazole also interferes directly with mitochondrial Adenosine triphosphate (ATP) production, leading to the activation of the adenosine monophosphate (AMP) -activated protein kinase pathway and subsequent inhibition of mTOR pathway (Head et al., 2015).
Testing Itraconazole on experimental settings was associated also with tumor hypoxia, as proved by induction of tumor-specific expression of Hypoxia-inducible factor 1-alpha (HIF1α), as well as decreased tumor micro-vessel load.
Taken together, these data support that Itraconazole may become a promising novel anti-angiogenic agent and In contrast to bevacizumab, Itraconazole is an inexpensive oral agent, currently available in a generic formulation and has been safely administered to thousands of patients as an antifungal drug with an excellent tolerance.
- Conditions
- Lung Cancer
- Being tested
- Itraconazole 200 mg, Chemotherapy
- Keywords
- Non small cell lung cancer, itraconazole, mtor inhibition, antiangiogensis, antifungal, anticancer, platinum based chemotherapy
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Itraconazole 200 mgDrug
itraconazole 200 mg oral tablet daily, on a 21-day cycle.
ChemotherapyDrug
intravenous doses of cisplatin 80 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 cycles.
Alternatively, Carboplatin may be used instead of Cisplatin, Carbplatin AUC 5 DAY 1 only Dose = AUC x (GFR + 25) IV in 250 mL Normal Saline over 30 minutes
| Study group | Role | What they receive |
|---|---|---|
| Itraconazole Arm | Experimental | Patients will receive intravenous doses of cisplatin 80 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 cycles + itraconazole 200 mg oral tablet daily, on a 21-day cycle.
Alternatively, Carboplatin may be used instead of Cisplatin, Carbplatin AUC 5 DAY 1 only Dose = AUC x (GFR + 25) IV in 250 mL Normal Saline over 30 minutes Receives: Drug: Itraconazole 200 mg; Drug: Chemotherapy |
| Control Arm | Active comparator | Patients will receive intravenous doses of cisplatin 80 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 cycles.
Alternatively, Carboplatin may be used instead of Cisplatin, Carbplatin AUC 5 DAY 1 only Dose = AUC x (GFR + 25) IV in 250 mL Normal Saline over 30 minutes Receives: Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
one year progression free survival
time from treatment initiation to either progression, death from any cause or lost to follow up.
Measured: 1 year
Secondary outcomes (4)
one year overall survival
time in months from time of diagnosis to death or date of last contact.
Measured: 1 year
Radiological response
To compare radiological response of patients with advanced lung cancer receiving platinum bases chemotherapy combined with itraconazole to those receiving platinum based chemotherapy only after 3 and 6 cycles of chemotherapy.
Measured: 18 weeks
quality of life
Patient's quality of life will be assessed at baseline, after 3 cycles, and at the end of chemotherapy treatment using EORTC modules specific to lung cancer.
Measured: 18 weeks
Adverse effects of Itraconazole.
Incidence and severity will be evaluated using National Cancer Institute-Common Toxicity Criteria for adverse events (CTCAE V4.03).
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2018
- Study start2 Jul 2018
- Primary completion2 Dec 2019 (estimated)
- Study completion2 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Interventional, Randomized, Controlled, Prospective, Open label, Phase II study.
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Asmaa Waheed Mohamed Mostafa, Ain Shams University
- Investigators
- Amr Shafik Tawfik, MD, Principal investigator, oncology department at Ain shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03664115
- Sponsor's protocol ID
- 00000017585
- Status last verified
- Sep 2018
- First submitted
- 1 Sep 2018
- Last updated
- 10 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: According to the sharing protocol of the official affliation
Publications
Mohamed AW, Elbassiouny M, Elkhodary DA, Shawki MA, Saad AS. The effect of itraconazole on the clinical outcomes of patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: a randomized controlled study. Med Oncol. 2021 Feb 9;38(3):23. doi: 10.1007/s12032-021-01475-0.
PubMed 33559053
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Itraconazole on the Clinical Outcomes of Patients With Advanced Non Small Cell Lung Cancer Receiving Platinum Based Chemotherapy
- ClinicalTrials.gov ID
- NCT03664115
- Acronym / sponsor ID
- 00000017585
- Conditions
- Lung Cancer
- Keywords
- Non small cell lung cancer, itraconazole, mtor inhibition, antiangiogensis, antifungal, anticancer, platinum based chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 2 Jul 2018 (actual)
- Primary completion
- 2 Dec 2019 (estimated)
- Study completion
- 2 Dec 2020 (estimated)
- First posted
- 10 Sep 2018 (actual)
- 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.
Circulating levels of angiogenic factors have been correlated with aggressive tumor growth, prediction of metastasis and prognosis in a wide range of solid tumors, including non-small cell lung cancer.
Food and Drug Administration (FDA) approved Itraconazole as an anti-angiogenic agent including both Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), and inhibited phosphorylation of the primary angiogenic receptors for these factors in 2007 and also known as an inhibitor of Hedgehog signalling, AKT (protein kinase B)/mechanistic target of rapamycin (mTOR) signaling adding its induction of autophagic cell death function based on cellular and laboratory studies, and allowed its use in phase II trials in prostate, lung and skin cancer.
Itraconazole also interferes directly with mitochondrial Adenosine triphosphate (ATP) production, leading to the activation of the adenosine monophosphate (AMP) -activated protein kinase pathway and subsequent inhibition of mTOR pathway (Head et al., 2015).
Testing Itraconazole on experimental settings was associated also with tumor hypoxia, as proved by induction of tumor-specific expression of Hypoxia-inducible factor 1-alpha (HIF1α), as well as decreased tumor micro-vessel load
Detailed description
Lung cancer is the leading cause of cancer death in the United States
The American Cancer Society estimates lung cancer incidence in the United States for 2018 to be about 234,030 and about 154,050 deaths.
In 2012, GLOBOCAN estimated that 1.8 million people were diagnosed with lung cancer, accounting for about 13% of total cancer diagnoses.
Lung cancer death rates declined 45% from 1990 to 2015 among men and 19% from 2002 to 2015 among women. From 2005 to 2014, the rate of new lung cancer cases dropped by 2.5% per year in men and 1.2% per year in women, These differences reflect historical patterns in tobacco use, where women began smoking in large numbers many years later than men, and were slower to quit .
World Health Organization (WHO) divides lung cancer into 2 major classes based on its biology, therapy, and prognosis: non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
The NSCLC subtype accounts for 87% of lung cancer cases with its most common types to be adenocarcinomas where it is approximately 40% of lung cancers.
Different factors like age, Performance state, co-morbidities, histology, molecular pathology and last but not least; the patient's preferences should be taken into account along the treatment strategy after a multidisciplinary tumor board discussion, to allow adequate and careful evaluation of the available data to reach the most appropriate management plan and treatment modality for each patient individually (Ung et al., 2016).
Platinum doublets Chemotherapy should be considered in all stage IV and inoperable stage III NSCLC patients with epidermal growth factor receptor (EGFR) and Anaplastic lymphoma kinase (ALK) negative disease, without major comorbidities and Performance state 0-2.
Circulating levels of angiogenic factors have been correlated with aggressive tumor growth, prediction of metastasis and prognosis in a wide range of solid tumors, including non-small cell lung cancer.
Food and Drug Administration (FDA) approved Itraconazole as an anti-angiogenic agent including both Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), and inhibited phosphorylation of the primary angiogenic receptors for these factors in 2007 and also known as an inhibitor of Hedgehog signalling, AKT (protein kinase B)/mechanistic target of rapamycin (mTOR) signaling adding its induction of autophagic cell death function based on cellular and laboratory studies, and allowed its use in phase II trials in prostate, lung and skin cancer.
Itraconazole was proved to be among one of the most potent and selective inhibitors of endothelial cell proliferation.
Itraconazole also interferes directly with mitochondrial Adenosine triphosphate (ATP) production, leading to the activation of the adenosine monophosphate (AMP) -activated protein kinase pathway and subsequent inhibition of mTOR pathway (Head et al., 2015).
Testing Itraconazole on experimental settings was associated also with tumor hypoxia, as proved by induction of tumor-specific expression of Hypoxia-inducible factor 1-alpha (HIF1α), as well as decreased tumor micro-vessel load.
Taken together, these data support that Itraconazole may become a promising novel anti-angiogenic agent and In contrast to bevacizumab, Itraconazole is an inexpensive oral agent, currently available in a generic formulation and has been safely administered to thousands of patients as an antifungal drug with an excellent tolerance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Interventional, Randomized, Controlled, Prospective, Open label, Phase II study.
| Arm | Type | Receives |
|---|---|---|
| Itraconazole Arm | Experimental | Drug: Itraconazole 200 mg, Drug: ChemotherapyPatients will receive intravenous doses of cisplatin 80 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 cycles + itraconazole 200 mg oral tablet daily, on a 21-day cycle. Alternatively, Carboplatin may be used instead of Cisplatin, Carbplatin AUC 5 DAY 1 only Dose = AUC x (GFR + 25) IV in 250 mL Normal Saline over 30 minutes |
| Control Arm | Active comparator | Drug: ChemotherapyPatients will receive intravenous doses of cisplatin 80 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 cycles. Alternatively, Carboplatin may be used instead of Cisplatin, Carbplatin AUC 5 DAY 1 only Dose = AUC x (GFR + 25) IV in 250 mL Normal Saline over 30 minutes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Stage IV NSCLC patients who have not received chemotherapy for metastatic disease management yet or inoperable locally recurrent Stage III NSCLC after concurrent chemoradiotherapy.
- ECOG 0-2.
- Age >18 years.
- Adequate bone marrow reserve (white blood cells [WBC] ≥ 3.5 × 109 /L, neutrophils ≥ 1.5 × 109 /L, platelets ≥ 100 × 109 /L, and hemoglobin ≥ 9.0 gm/dL).
Key exclusion criteria (8 listed)
- Inadequate liver function (bilirubin > 1.5 times upper normal limit [ULN] and alanine transaminase [ALT] or aspartate transaminase [AST] > 3.0 ULN or up to 5.0 UNL in the presence of hepatic metastases).
- Inadequate renal function (creatinine > 1.25 times ULN, creatinine clearance < 50mL/min).
- Serious comorbid systemic disorder incompatible with the study.
- Presence of other primary malignancy.
- Patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF.
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 |
|---|---|---|
| Itraconazole 200 mgitraconazole 200 mg oral tablet daily, on a 21-day cycle. | Drug | Itraconazole Arm |
| Chemotherapyintravenous doses of cisplatin 80 mg/m2 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks for a maximum of 6 cycles. Alternatively, Carboplatin may be used instead of Cisplatin, Carbplatin AUC 5 DAY 1 only Dose = AUC x (GFR + 25) IV in 250 mL Normal Saline over 30 minutes | Drug | Control Arm, Itraconazole Arm |
Primary outcome
one year progression free survival
Time frame: 1 year
time from treatment initiation to either progression, death from any cause or lost to follow up.
4 secondary outcomes
one year overall survival
Time frame: 1 year
Radiological response
Time frame: 18 weeks
quality of life
Time frame: 18 weeks
Adverse effects of Itraconazole.
Time frame: 18 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2018.
- Derived from this study: PubMed 33559053Mohamed AW, Elbassiouny M, Elkhodary DA, Shawki MA, Saad AS. The effect of itraconazole on the clinical outcomes of patients with advanced non-small cell lung cancer receiving platinum-based chemotherapy: a randomized controlled study. Med Oncol. 2021 Feb 9;38(3):23. doi: 10.1007/s12032-021-01475-0.
- Individual participant dataSharing planned: Undecided. According to the sharing protocol of the official affliation
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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.
Amr Shafik Tawfik, MD principal investigator
oncology department at Ain shams University
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 Itraconazole 200 mg and Chemotherapy in people with Lung Cancer, run by Ain Shams University at 1 site in Egypt.
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 4 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 10 Sep 2018. 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 Egypt. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Asmaa WH Mohamed, Master (01003538597, drasmaa_wahid@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
one year progression free survival (time frame: 1 year). 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 NCT03664115, which also lists 1 linked publication.
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 10 Sep 2018.