Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Osimertinib

Cobicistat

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Cytochrome P-450 CYP3A Inhibitors

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Cobicistat will serve as experimental drugs, and will be added to the regular treatment with osimertinib. Combination-treatment will be started at 150 milligram cobicistat, and can be increased to a maximum daily dose of 600 milligram cobicistat (four times 150 milligram).

Cobicistat will be added to the treatment with osimertinib. The initial dose will be 150 mg cobicistat, which equals the dose used in the treatment of HIV-infected patients. If this dose is well tolerated and the increase in exposure of osimertinib is not sufficient, the dose of cobicistat will gradually be escalated to 600 mg per day (150 mg cobicistat, four times per day).

Sander Croes, MSc, PhD

The main objective of this study is to evaluate if systemic exposure of osimertinib (i.e. AUC) is increased when osimertinib is co-administered with cobicistat in patients with relatively low plasma trough concentration while receiving the standard osimertinib dose.

Osimertinib is a new targeted agent registered for the treatment of patients with EGFR-mutated NSCLC. However, the costs of those new treatments are extremely high. Osimertinib is mainly metabolized by CYP3A4, and partially by CYP3A5. Combination of osimertinib with a strong CYP3A4-inhibitor may result in a smaller first-pass effect and a decreased clearance of osimertinib, thereby increasing the exposure to osimertinib.

Cobicistat is a strong CYP3A4-inhibitor, this mechanism may be used to boost osimertinib, as is done for other drugs, mainly drugs used to treat HIV-infected patients.

Using this personalized treatment approach and combining the concepts of therapeutic drug monitoring (TDM) and pharmacokinetic boosting, osimertinib therapy could become much more cost-effective. By reducing the necessary dose of osimertinib, this strategy may ultimately result in a significant reduction in drug costs, as the additional expenditure for the CYP3A4 inhibitor and blood sample analysis are negligible compared to the price of osimertinib.

In this study a group of patients will receive cobicistat as add-on on their regular treatment with osimertinib. All patients experience low osimertinib trough concentration levels when treated with the regular osimertinib dose (80 mg per day).

Pharmacokinetic Boosting of Osimertinib

Pharmacokinetic Boosting of Osimertinib in Patients With Non-small Cell Lung Cancer.

Exposure to osimertinib will be measured at the start of the study and after three weeks of treatment with cobicistat. This will be done by measuring the concentration of osimertinib four times during the day (pre-dose and two, four and eight hour post-dose), which will be used to calculate the AUC of osimertinib.

The safety of the combination therapy will be evaluated and scored using NCI CTCAE v4.0. The investigators will evaluate the number of patients that experience treatment-related adverse events. Additionally, the investigators will describe the adverse events which are most common in the lung cancer patients.

Participants will be asked to keep up a patient diary with problems they have experienced during the study.

The maximum plasma of osimertinib will be determined

The Netherlands Cancer Institute

ZonMw: The Netherlands Organisation for Health Research and Development

Academisch Ziekenhuis Maastricht

Researcher

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Biphenotypic, Acute

Lymphoma

Acute Disease

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Acute Leukemia of Ambiguous Lineage

Lymphosarcoma

Clotrimazole

Miconazole

Fluconazole

Antifungal Agents

Isavuconazole

Phase 1: Oral revumenib; sequential cohorts of escalating dose levels of revumenib to identify the MTD and RP2D. Participants will be enrolled in 1 of 6 dose-escalation arms:

* Arm A: Participants not receiving any strong CYP3A4 inhibitor/inducers or fluconazole
* Arm B: Participants receiving any strong CYP3A4 inhibitors for antifungal prophylaxis
* Arm C: Participants receiving revumenib and cobicistat
* Arm D: Participants receiving fluconazole for antifungal prophylaxis
* Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers
* Arm F: Participants receiving isavuconazole for antifungal prophylaxis

Phase 2: Oral revumenib; Following the determination of the RP2D in Phase 1, 3 indication-specific expansion cohorts will be enrolled as follows:

* Cohort 2A: Participants with KMT2Ar ALL/MPAL
* Cohort 2B: Participants with KMT2Ar AML
* Cohort 2C: Participants with NPM1m AML

revumenib

Phase 1 Arm C participants will receive 150 mg cobicistat daily.

cobicistat

Syndax Pharmaceuticals

Manjyot Nanhwan

Shirley Sian

George Yaghmour

Kyle Denzel Cobarrubias

Katelyn Anttila

Terri Peterson, RN

Shannon Gleason, MLS, CCRC

Aflac Cancer & Blood Disorders Center Referral

Howie Weiner, CCRP

David Dickens, MD

Morgan Johnson

Lindsay Rae

Hannah Hartman

Madeline Stowe

Kait Tkachuk

Karen Fehn

Joel Victor

Linda Brown

Kris Mahadeo

Nadia Osman

Molly Brandenburg

OHSU Knight Cancer Institute Clinical Trials

Ronan Swords, MD

Robin E Blauser, BSN RN

Ghayas Issa, MD

Farha Inam

Cathy Tran

Ashish Bajel

Shaun Fleming, MD

Carolyn Grove, MD

Matthew Greenwood, MD

Andre Schuh, MD

Aiman Siddiqi

Alexandre Deloire

Mael Heiblig

Mathilde Petit

Stephanie De Botton

Benjamin Bietsch

Melanie Koch

Hanoun Maher

Dirk Reinhardt

Berit Riemer

Annamaria Brioli

Conny Schuck

Michael Kuehn

Hadil Asadi

Baher Krayem

Dafna Laufer

Yishai Ofran

Leah Greenfeld

Boaz Nachmias

Lana Saada

Galia Stemer

Contact: Sharon Hercman Dachevsky

Ofir Wolach

Yuval Carmel

Irina Armitai

Francesco Ingletto

Cristina Papayannidis

Federica Frabetti

Giovanni Marconi

Irene Mutterle

Corinna Greco

Andrejus Cernovas

Andrius Zucenka

Secretary Trial and Data Centrum

Michael Zwaan

Anna Valer

Montserrat Arnan Sangerman

Laura More

Eduardo Rodriguez-Arboli

Elisa Gonzales

Pau Montesinos Fernandez

Angela R Smith, M.D.

Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of revumenib in participants with acute leukemia.

In Phase 2, participants will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib.

Phase 1: Oral revumenib; sequential cohorts of escalating dose levels of revumenib to identify the MTD and RP2D. Participants will be enrolled in one of six dose-escalation arms:

Arm A: Participants not receiving any strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducers or fluconazole.

Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis.

Arm C: Participants receiving revumenib and cobicistat.

Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.

Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers.

Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis.

In Phase 2, participants will be enrolled in 3 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib:

* Cohort 2A: Participants with KMT2Ar acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia (MPAL)
* Cohort 2B: Participants with KMT2A AML
* Cohort 2C: Participants with NPM1m AML

Phase 1 will employ an accelerated titration design. The dose escalation will follow a modified Fibonacci sequence.

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

A Phase 1/2, Open-label, Dose-Escalation and Dose-Expansion Cohort Study of SNDX-5613 in Patients With Relapsed/Refractory Leukemias, Including Those Harboring an MLL/KMT2A Gene Rearrangement or Nucleophosmin 1 (NPM1) Mutation

Assessed by the NCI CTCAE version 5.0 (Phase 1)

Maximum plasma concentration (Cmax) of revumenib and relevant metabolites (Phase 1)

Time to observed maximum plasma concentration of revumenib and relevant metabolites (Phase 1)

Area under the plasma concentration-time curve from time 0 to time of last measurable concentration (AUC0-t) of revumenib and relevant metabolites (Phase 1)

To assess the complete remission (CR) and complete remission with partial hematologic recovery (CRh) rate (Phase 2)

Assessed by the NCI CTCAE version 5.0 (Phase 2)

Transfusion independence is defined as any transfusion-free period lasting for at least 56 consecutive days

To assess the composite definition of complete remission (CRc) rate (Phase 2)

To assess the overall response rate (ORR) of revumenib (Phase 2)

To assess the time to response (TTR) of revumenib (Phase 2)

To assess the duration of response (DOR) of revumenib (Phase 2)

To assess the event free survival (EFS) of revumenib (Phase 2)

To assess overall survival (OS) of revumenib (Phase 2)

Cmax of revumenib and relevant metabolites (Phase 2)

Tmax of revumenib and relevant metabolites (Phase 2)

AUC0-t of revumenib and relevant metabolites (Phase 2)

Participants with unresectable, locally advanced or metastatic solid tumors or primary CNS tumors harboring BRAF fusions, will receive 900 mg of plixorafenib administered with 150 mg of cobicistat once daily (QD), continuously in 3-weeks cycles until disease progression, unacceptable toxicity, or other reason for withdrawal.

Participants with recurrent primary CNS tumors harboring BRAF V600E mutations will receive 900 mg of plixorafenib administered with 150 mg of cobicistat QD, continuously in 3-week cycles until disease progression, unacceptable toxicity, or other reason for withdrawal.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pharmacokinetic Boosting of Osimertinib	NCT03858491	Non Small Cell ...	Cobicistat	18 Years -	Academisch Ziekenhuis Maastricht
A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation	NCT04065399	Acute Myeloid L... Acute Lymphobla... Mixed Lineage A... Mixed Phenotype... Acute Leukemia ...	revumenib cobicistat	30 Days -	Syndax Pharmaceuticals
A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations	NCT05503797	Cancer Harborin...	Plixorafenib Cobicistat	10 Years -	Fore Biotherapeutics
Pharmacokinetic Boosting of Olaparib to Improve Exposure, Tolerance and Cost-effectiveness	NCT05078671	Cancer	Olaparib Cobicistat	18 Years -	Radboud University Medical Center
A Study to Assess the Efficacy and Safety of FORE8394 in Participants With Cancer Harboring BRAF Alterations	NCT05503797	Cancer Harborin...	Plixorafenib Cobicistat	10 Years -	Fore Biotherapeutics
Improving Osimertinib Exposure and Cost-effectiveness Using Pharmacokinetic Boosting With Cobicistat	NCT05748093	Non-small Cell ...	Cobicistat	18 Years -	Maastricht University Medical Center
A Trial of Cobicistat and Gemcitabine and Nab-Paclitaxel in Patients With Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma	NCT05494866	CYP3A Inhibitor Advanced Stage ... Pancreatic Canc... Pancreatic Aden... Pancreatic Neop...	Cobicistat Oral... Gemcitabin Nab paclitaxel	18 Years -	German Cancer Research Center
A Trial of Cobicistat and Gemcitabine and Nab-Paclitaxel in Patients With Advanced Stage or Metastatic Pancreatic Ductal Adenocarcinoma	NCT05494866	CYP3A Inhibitor Advanced Stage ... Pancreatic Canc... Pancreatic Aden... Pancreatic Neop...	Cobicistat Oral... Gemcitabin Nab paclitaxel	18 Years -	German Cancer Research Center

Spots Global Cancer Trial Database for cobicistat

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

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