Itraconazole in Non Small Cell Lung Cancer

NCT03664115 | Unknown Phase 2

• 1 other identifier: 00000017585
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Conditions

Lung Cancer

Keywords

Non small cell lung cancer; itraconazole; mtor inhibition; antiangiogensis; antifungal; anticancer; platinum based chemotherapy

Outcome Measures

Primary Outcomes (1)

• one year progression free survival

  time from treatment initiation to either progression, death from any cause or lost to follow up.

  1 year

Secondary Outcomes (4)

• one year overall survival

  1 year

• Radiological response

  18 weeks

• quality of life

  18 weeks

• Adverse effects of Itraconazole.

  18 weeks

Study Arms (2)

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

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

Drug: Chemotherapy

Interventions

Itraconazole 200 mg DRUG

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

Itraconazole Arm

Chemotherapy DRUG

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

Control Arm; Itraconazole Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

oncology department Ain shams university

Cairo, 11591, Egypt

RECRUITING

Related Publications (1)

• 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.

  PMID: 33559053 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Itraconazole; Drug Therapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Therapeutics

Study Officials

• Amr Shafik Tawfik, MD

  oncology department at Ain shams University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Asmaa WH Mohamed, Master

CONTACT

01003538597; drasmaa_wahid@hotmail.com

Amr Sh Tawfik, MD

CONTACT

01227888314; docshak76@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Model Details: Interventional, Randomized, Controlled, Prospective, Open label, Phase II study.

Study Record Dates

• First Submitted: September 1, 2018
• First Posted: September 10, 2018
• Study Start: July 2, 2018
• Primary Completion: December 2, 2019
• Study Completion: December 2, 2020
• Last Updated: September 10, 2018

Record last verified: 2018-09

Locations

EG (1)