Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Gemcitabine

Carboplatin

Cisplatin

Itraconazole

Clotrimazole

Miconazole

Hydroxyitraconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

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

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

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

Itraconazole 200 mg

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

Chemotherapy

Asmaa WH Mohamed, Master

Amr Sh Tawfik, MD

Amr sh Tawfik, MD

Amr Shafik Tawfik, MD

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

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.

Interventional, Randomized, Controlled, Prospective, Open label, Phase II study.

Itraconazole in Non Small Cell Lung Cancer

The Effect of Itraconazole on the Clinical Outcomes of Patients With Advanced Non Small Cell Lung Cancer Receiving Platinum Based Chemotherapy

According to the sharing protocol of the official affliation

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

time in months from time of diagnosis to death or date of last contact.

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.

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.

Incidence and severity will be evaluated using National Cancer Institute-Common Toxicity Criteria for adverse events (CTCAE V4.03).

Ain Shams University

Doctor

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Amino Acids

Lysine

Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Participants with advanced R/R MCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Participants with advanced R/R FL or MZL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

Participants with advanced R/R DLBCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first.

All patients will receive treatment with the investigational product AZD0466 via intravenous infusion.

AZD0466

This study evaluates the safety, tolerability, PK, and preliminary efficacy of AZD0466 as monotherapy or in combination with other anticancer agents in patients with advanced NHL

This is a modular Phase I/II, open-label, dose escalation and expansion, multicentre Study. The study consists of individual modules, each evaluating the safety and tolerability of AZD0466 as monotherapy or with a specific combination treatment. The initial components are the core protocol, which contains information applicable to all modules, and Module 1.

Module 1 will evaluate the safety, tolerability, PK, and preliminary efficacy of AZD0466 monotherapy and will include 2 parts. Part A dose escalation and Part B dose expansion cohorts. Part A will enrol patients with advanced B-NHL and once the RP2D has been determined, Part B may open to further explore the preliminary anticancer efficacy of AZD0466 monotherapy in patients with selected lymphoid malignancies.

Part A: Phase 1 dose setting to assess the safety and tolerability and determine dose(s) and schedule(s) to be evaluated in Part B.

Part B: Phase 1b/2a dose expansion to assess the efficacy of AZD0466 in 3 select patient populations: relapsed/refractory (R/R) mantle cell lymphoma (MCL) (Cohort B1), R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) (Cohort B2), and R/R diffuse large B-cell lymphoma (DLBCL) (Cohort B3).

A Phase I/II Study of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Advanced Non-Hodgkin Lymphoma

A Modular Phase I/II, Open-label, Dose Escalation and Expansion, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Patients With Advanced Non-Hodgkin Lymphoma.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

To assess the safety and tolerability and identify the MTD and/or RP2D of AZD0466 as monotherapy or in combination with anticancer agents in patients with R/R B-NHL

To assess the preliminary efficacy of AZD0466 as monotherapy or in combination with other anticancer agents in patients with R/R B-NHL. ORR is defined as the proportion of participants who have a tumour response (complete Response \[CR\] and partial response \[PR\]).

Assessment of the safety and tolerability of AZD0466 as monotherapy or in combination with anticancer agents in patients with R/R B-NHL

To assess the efficacy of AZD0466 as monotherapy or in combination with anticancer agents by evaluation of tumour response and OS in patients with R/R B-NHL

To assess the efficacy of AZD0466 as monotherapy or in combination with anticancer agents by evaluation of DoR defined as the time from the date of first documented response until the date of documented progression or death due to any cause in the absence of disease progression.

To assess the efficacy of AZD0466 as monotherapy or in combination with anticancer agents by evaluation of TTR defined as the time from date of first dose until the date of first documented objective response.

To assess the efficacy of AZD0466 as monotherapy or in combination with anticancer agents by evaluation of PFS is defined as the time from date of first dose to date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from treatment or receives another anti-lymphoma therapy prior to progression.

To assess the efficacy of AZD0466 as monotherapy or in combination with anticancer agents by evaluation of OS defined as the time from date of first dose until death due to any case regardless of whether patient withdraws from treatment or receives another anti-lymphoma therapy.

Assessment of AZD4320 to characterise the PK profile of AZD0466

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Itraconazole in Non Small Cell Lung Cancer	NCT03664115	Lung Cancer	Itraconazole 20... Chemotherapy	18 Years -	Ain Shams University
A Phase I/II Study of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Advanced Non-Hodgkin Lymphoma	NCT05205161	Non-Hodgkin Lym...	AZD0466	18 Years - 130 Years	AstraZeneca
A Phase I/II Study of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Advanced Non-Hodgkin Lymphoma	NCT05205161	Non-Hodgkin Lym...	AZD0466	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for anticancer

Every month we try and update this database with for anticancer cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for anticancer

Every month we try and update this database with for anticancer cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for anticancer cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.