Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Etoposide

Cytarabine

Daunorubicin

Etoposide phosphate

Atovaquone

Gemtuzumab

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Induction I ADE: cytarabine, daunorubicin, etoposide 10+3+5, atovaquone daily

Induction I DA: daunorubicin, cytarabine 3+10 with GO: gemtuzumab ozogamicin, atovaquone daily

Patients will receive standard of care MRC based Induction chemotherapy (such as ADE 10+3+5 with daily atovaquone dosing starting on day 6. In order to accommodate potential drug shortages modifications to ADE 10+3+5 that retain the MRC based induction backbone regimen of DA are allowed (see second Arm). These include but are not limited to substitution of etopophos for etoposide, exclusion of etoposide, use of CPX-351 (VYXEOS (daunorubicin and cytarabine) liposome) only, and daunorubicin and cytarabine (DA) + gemtuzumab ozogamicin (GO).

Patients will be monitored for adherence to and tolerance of daily dosing of atovaquone. Peripheral blood (PB) and bone marrow plasma samples will be obtained to measure atovaquone concentrations.

As part of routine Induction 1 chemotherapy (ADE 10+3+5)

As part of routine Induction 1 chemotherapy(DA 3+10 + GO)

Gemtuzumab Ozogamicin

Alexandra Stevens, MD

This study will test daily dosing of atovaquone at established pneumocystis jiroveci pneumonia (PJP) prophylaxis dosing in combination with standard induction chemotherapy for de novo AML. The primary objectives are to determine the frequency of omission of atovaquone doses due to standard induction chemotherapy toxicity, to quantify the steady-state plasma levels of atovaquone, and to determine the time to achievement of steady state atovaquone levels in this population.

Standard cytotoxic chemotherapy is based on the Medical Research Council (MRC) backbone of cytarabine, and daunorubicin. This combination of chemotherapy is highly myelosuppressive and can lead to oral aversions, dietary intolerance, and gastrointestinal infections necessitating holding of oral drugs. Because of the toxicity of the best currently available therapy, new drugs that are considered for incorporation into existing treatment regimens will ideally have a tolerable side effect profile. This study will evaluate the tolerability of incorporating the orally bioavailable drug atovaquone in combination with standard cytotoxic induction chemotherapy for newly diagnosed pediatric AML patients. Therefore, quantifying the frequency with which atovaquone is held due to a side effect of therapy is crucial information to gather in this population.

Choice of Induction I regimen is at the treating physician's discretion (will be influenced based on drug availability)

Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML)

A Trial of Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML) in Children, Adolescents, and Young Adults (ATACC AML)

The investigators will determine plasma levels of atovaquone at the following time points: Day 6, 11, 13, 15, 18, 20, 22, 29 and on the day of the end of induction bone marrow (BM) assessment (generally around Day 36).

To quantify the frequency of atovaquone doses omitted due to standard MRC related toxicity. Administration of doses of atovaquone will be monitored while the patient is hospitalized in the electronic medical record and abstracted to case report forms. Families will also be given a diary to complete.

Time to achieving steady state concentrations of atovaquone when given in combination with standard chemotherapy in children with de novo AML will be determined using stepwise tests of linear trend.

William Marsh Rice University

Baylor College of Medicine

M.D. Assistant Professor

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Hypoxia

Neoplasms, Glandular and Epithelial

Signs and Symptoms, Respiratory

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Proguanil

Atovaquone suspension, 750mg/5ml bd and 1000mg (6.25ml) bd for 7-17 days. Device: PET-CT, Device: DWI-MRI

Atovaquone has an EU marketing authorisation (held by Glaxo Wellcome UK Ltd) and is indicated for acute treatment of mild to moderate Pneumocystis pneumonia (PCP). It is also used in combination with proguanil for malaria prophylaxis.

Geoff Higgins, MBChB, MRCP, FRCR

Solid tumours often have highly disorganised vasculature that results in low oxygenation. This combined with high metabolic rates leads to oxygen demand outstripping supply causing tumour hypoxia. Hypoxia drives multiple cellular processes involved in the hallmarks of cancer. Tumour hypoxia also decreases the effectiveness of anticancer treatments. This is especially true for patients treated with radiotherapy since it has been long recognised that hypoxic tumour cells require 3 times the dose of radiation to cause the same amount of cell death as cells irradiated under normal oxygen conditions.

To date, the majority of attempts at overcoming tumour hypoxia have focused on increasing oxygen supply. However, such techniques have produced modest benefits at best and subsequently have not been adopted into current clinical practice.

An interesting alternative approach to tackling tumour hypoxia is to decrease oxygen 'demand' by reducing tumour oxygen consumption. This strategy has been suggested to be more effective in reducing hypoxia than previous methods aimed at increasing oxygen delivery.

Pre-clinical data demonstrates that the commonly prescribed anti-protozoal drug atovaquone significantly reduces oxygen consumption in a variety of tumour cell lines in vitro. This reduction in oxygen consumption leads to a profound reduction in tumour hypoxia in animal models. It is anticipated that if these effects on tumour hypoxia could be reproduced in humans, that their tumours could be rendered markedly more sensitive to radiotherapy.

This window of opportunity trial will assess whether atovaquone significantly reduces tumour hypoxia in adult patients referred for surgery with suspected non-small cell lung cancer. This will be assessed using a combination of functional imaging and circulating markers of hypoxia. If atovaquone is demonstrated to result in a reduction in tumour hypoxia, larger clinical trials will be conducted to determine whether this well-tolerated and inexpensive agent improves radiotherapy efficacy and clinical outcomes.

Atovaquone as Tumour HypOxia Modifier

Pre-operative Window of Opportunity Study of the Effects of Atovaquone on Hypoxia in Non-small Cell Lung Carcinoma

HPLC (high pressure liquid chromatography) based measurement of plasma level and tumour level of atovaquone

Comparison of histological hypoxia and vasculature parameters with prior imaging measuring hypoxia, perfusion, and glycolysis

Comparison of serological hypoxia parameters with immunohistochemistry on pimonidazole staining

Hypoxia metagene signature expression and Individual tests to measure gene expression/mutation

Progression-free survival and overall survival

Average hypoxic volume reduction (%) in 18F-fluoromisonidazole (18F-MISO)/18F-fluoroazomycin arabinoside (18F-FAZA) uptake as detected by hypoxia-PET(positron emission tomography)-CT scans.

Changes in tumour blood flow measured by perfusion CT, DWI-MRI, DCE-MRI and PET kinetic modelling

Changes in hypoxia-PET-CT derived hypoxic volumes compared with changes in plasma levels of serological markers of hypoxia

Comparison of hypoxia-PET-CT, perfusion CT, serological tests, diffusion-weighted imaging (DWI-MRI) and Dynamic contrast-enhanced MRI (DCE-MRI) derived parameters

University of Oxford

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Adenocarcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cystadenocarcinoma, Serous

Cystadenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Ovarian Cancer

Ovarian Epithelial Cancer

Adenocarcinoma of the Appendix

Patients receive atovaquone PO on study. Patients also undergo CT and biopsy or paracentesis throughout the study.

Biopsy

Computed Tomography

Paracentesis

Namita Khanna, MD, MSPH

Nina Kimball

Maisey S Ratcliffe

This phase II trial test tests how well repurposing atovaquone works in treating patients with platinum-resistant ovarian cancer. Atovaquone is used for the treatment or prevention of certain infections. Atovaquone is in a class of medications called antiprotozoal agents. It works by stopping the growth of certain types of protozoa that can cause pneumonia. Giving atovaquone may be effective in treating platinum-resistant ovarian cancer and result in improved outcomes compared to standard chemotherapy regimens.

PRIMARY OBJECTIVE:

I. To determine progression free survival of twenty-eight patients with platinum-resistant ovarian cancer treated with atovaquone.

SECONDARY OBJECTIVES:

I. To determine clinical benefit rate (complete response, partial response or stable disease) at six months.

II. To determine overall survival. III. To quantitate the on-target STAT3 inhibitory effect of atovaquone on STAT3-dependent gene transcription.

IV. To quantitate changes of the tumor immune infiltrate by inhibition of STAT3 with atovaquone.

OUTLINE:

Patients receive atovaquone orally (PO) on study. Patients also undergo computed tomography (CT) and biopsy or paracentesis throughout the study.

After completion of study treatment, patients are followed up for 30 days and then every 6 month thereafter.

Repurposing Atovaquone for the Treatment of Platinum-Resistant Ovarian Cancer

Phase II Clinical Trial Repurposing Atovaquone for the Treatment of Platinum-Resistant Ovarian Cancer

Will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median PFS will be estimated using the Brookmeyer-Crowley approach.

Clinical benefit rate is defined as complete response, partial response, and/or stable disease at six months. Clinical response will be assessed every 6 weeks for the first 24 months and every 12 weeks thereafter using Response Evaluation Criteria in Solid Tumors 1.1 criteria. Will be estimated as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method.

OS will be estimated using the Kaplan-Meier method, and median survival will be calculated. A 95% confidence interval will be estimated using the Brookmeyer-Crowley approach.

Safety will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Frequencies and percentages will be used to summarize safety events.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML)	NCT03568994	Acute Myeloid L...	Atovaquone Cytarabine Daunorubicin Etoposide Gemtuzumab Ozog...	1 Month - 20 Years	Baylor College of Medicine
Atovaquone as Tumour HypOxia Modifier	NCT02628080	Carcinoma, Non-...	Atovaquone	18 Years -	University of Oxford
Atovaquone as Tumour HypOxia Modifier	NCT02628080	Carcinoma, Non-...	Atovaquone	18 Years -	University of Oxford
Repurposing Atovaquone for the Treatment of Platinum-Resistant Ovarian Cancer	NCT05998135	Ovarian High Gr... Platinum-Resist...	Atovaquone Biopsy Computed Tomogr... Paracentesis	18 Years -	Emory University

Spots Global Cancer Trial Database for atovaquone

Every month we try and update this database with for atovaquone 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 atovaquone

Every month we try and update this database with for atovaquone 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 atovaquone 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.