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Itraconazole in Non Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT03664115
Recruitment Status : Recruiting
First Posted : September 10, 2018
Last Update Posted : September 10, 2018
Sponsor:
Information provided by (Responsible Party):
Asmaa Waheed Mohamed Mostafa, Ain Shams University

Brief 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.

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


Condition or disease Intervention/treatment Phase
Lung Cancer Drug: Itraconazole 200 mg Drug: Chemotherapy Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Interventional, Randomized, Controlled, Prospective, Open label, Phase II study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Itraconazole on the Clinical Outcomes of Patients With Advanced Non Small Cell Lung Cancer Receiving Platinum Based Chemotherapy
Actual Study Start Date : July 2, 2018
Estimated Primary Completion Date : December 2, 2019
Estimated Study Completion Date : December 2, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Itraconazole Arm

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

Drug: Itraconazole 200 mg
itraconazole 200 mg oral tablet daily, on a 21-day cycle.

Drug: Chemotherapy

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


Active Comparator: Control Arm

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

Drug: Chemotherapy

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





Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. one year overall survival [ Time Frame: 1 year ]
    time in months from time of diagnosis to death or date of last contact.

  2. Radiological response [ Time Frame: 18 weeks ]
    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.

  3. quality of life [ Time Frame: 18 weeks ]
    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.

  4. Adverse effects of Itraconazole. [ Time Frame: 18 weeks ]
    Incidence and severity will be evaluated using National Cancer Institute-Common Toxicity Criteria for adverse events (CTCAE V4.03).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Stage IV NSCLC patients who have not received chemotherapy for metastatic disease management yet or inoperable locally recurrent Stage III NSCLC after concurrent chemoradiotherapy.
  2. ECOG 0-2.
  3. Age >18 years.
  4. 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).

Exclusion Criteria:

  1. 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).
  2. Inadequate renal function (creatinine > 1.25 times ULN, creatinine clearance < 50mL/min).
  3. Serious comorbid systemic disorder incompatible with the study.
  4. Presence of other primary malignancy.
  5. Patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF.
  6. Patients with hypersensitivity to Itraconazole.
  7. Patients receiving any Cytochrome P450 (CYP 3A4) inhibitor as clarithromycin, diltiazem, verapamil, quinidine ….etc.
  8. Pregnant female patients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03664115


Contacts
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Contact: Asmaa WH Mohamed, Master 01003538597 drasmaa_wahid@hotmail.com
Contact: Amr Sh Tawfik, MD 01227888314 docshak76@gmail.com

Locations
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Egypt
oncology department Ain shams university Recruiting
Cairo, Egypt, 11591
Contact: Amr sh Tawfik, MD         
Contact: Asmaa WH Mohamed, Master    01003538597    drasmaa_wahid@hotmail.com   
Sponsors and Collaborators
Ain Shams University
Investigators
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Principal Investigator: Amr Shafik Tawfik, MD oncology department at Ain shams University

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Responsible Party: Asmaa Waheed Mohamed Mostafa, Doctor, Ain Shams University
ClinicalTrials.gov Identifier: NCT03664115     History of Changes
Other Study ID Numbers: 00000017585
First Posted: September 10, 2018    Key Record Dates
Last Update Posted: September 10, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: According to the sharing protocol of the official affliation

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Asmaa Waheed Mohamed Mostafa, Ain Shams University:
Non small cell lung cancer
itraconazole
mtor inhibition
antiangiogensis
antifungal
anticancer
platinum based chemotherapy

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cisplatin
Gemcitabine
Carboplatin
Itraconazole
Hydroxyitraconazole
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists