Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Pembrolizumab

Immunomodulating Agents

Eflornithine

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Ornithine

Difluoromethylornithine (DFMO) + Pembrolizumab Pre-treated or treatment naive advanced or metastatic NSCLC.

The phase I dose escalation will include a fixed dose of Pembrolizumab IV every 3 weeks and escalating doses of DFMO (three dose levels) to determine the maximum tolerated dose (MTD) to be used in the phase II portion of the trial.

DFMO level -1: Dose Level -1: 4500 mg/m2 by mouth (PO) once a day (QD).

DFMO Level 1: (start): 6750 mg/m2 PO QD

Dose Level 2: 9000 mg/m2 PO QD

Difluoromethylornithine (DFMO) + Pembrolizumab

Advanced/metastatic NSCLC who are immunotherapy naïve.

Pembrolizumab IV flat dose every 3 weeks

DFMO dose to be determined (TBD) based on maximum tolerated dose (MTD) and dose limiting toxicities (DLT) in Phase I dose escalation.

Dose Level -1: 4500 mg/m2 by mouth (PO) daily Dose Level 1: 6750 mg/m2 by mouth (PO) daily Dose Level 2: 9000 mg/m2 by mouth (PO) daily

Difluoromethylornithine

Anahid Aminpour

Jhanelle E. Gray, MD

Jhanelle E. Gray, M.D.

The purpose of this study is to establish the safety, toxicity, and tolerability of Difluoromethylornithine (DFMO) in combination with pembrolizumab in advanced/metastatic Non-Small Cell Lung Cancer (NSCLC). Researchers also want to investigate how effective DFMO is at treating patients with advanced/ metastatic NSCLC.

Targeting ODC as an Immunotherapeutic Target in STK11 (LKB1) Pathway-Deficient NSCLC (DFMO)

Targeting ODC as an Immunotherapeutic Target in STK11 (LKB1) Pathway-Deficient NSCLC

To determine the maximum tolerated dose (MTD) and recommended phase II dose (R2PD) of DFMO in combination with pembrolizumab. The MTD will be declared if 1 or fewer patients have a Dose limiting toxicity (DLT) in that dose level.

To determine the efficacy of DFMO in combination with pembrolizumab. Objective response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on modified RECIST guidelines version 1.1.

Progression-free survival will be measured from the start of treatment with pembrolizumab and DFMO until the documentation of disease progression or death due to any cause, whichever occurs first. For subjects who are alive and progression-free at the time of data cut-off for analysis, PFS will be censored at the last tumor assessment date.

Overall survival will be determined as the time from the start of treatment with pembrolizumab and DFMO until death due to any cause. For subjects who are alive at the time of data cut-off, OS will be censored on the last date when subjects are known to be alive.

H. Lee Moffitt Cancer Center and Research Institute

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Sulindac

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Sulindac alone, washout, DFMO alone, then combination of sulindac and DFMO

DFMO alone, followed by washout, sulindac alone, then combination of DFMO and sulindac

500 mg oral for 14 days, combined with sulindac for 15 days

difluoromethylornithine

150 mg oral for 15 days, combined with DFMO for 14 days

The purpose of this study is to determine the effects of 2 drugs (sulindac and Difluoromethylornithine (DFMO)) either alone or in combination on biomarkers found in urine.

Urinary Biomarker Study With Sulindac and Difluoromethylornithine

A Phase 2 Urinary Biomarker Study of Polyamine Inhibition With Sulindac and Difluoromethylornithine (DFMO)

Measure initial variability in levels of urinary biomarkers prior to initiation of drug treatment. Three blood draws over the first 14 days will be used to assess baseline variability.

Measure urinary biomarker dcSAM after 14 days of single agent DFMO. Measure urinary biomarker dcSAM after 14 days of single agent DFMO for treatment arm where DFMO alone is started week 2 (Treatment sequence A).

Measure urinary biomarker dcSAM after 14 days of single agent sulindac. Measure urinary biomarker dcSAM after 14 days of single agent sulindac for treatment arm where sulindac alone is started week 2 (Treatment sequence B).

Measure urinary biomarker dcSAM after 14 days of single agent DFMO for treatment arm where DFMO alone is started week 10 (Treatment sequence B)

Measure urinary biomarker dcSAM after 14 days of single agent sulindac. Measure urinary biomarker dcSAM after 14 days of single agent sulindac for treatment arm where sulindac alone is stated week 10 (Treatment sequence A).

Quantitate dietary polyamine levels over the course of the study and evaluate the effects on biomarkers evaluated in the primary outcome measures.

University of Arizona

Cancer Prevention Pharmaceuticals, Inc.

Associate Professor, Cellular and Molecular Medicine

Skin and Connective Tissue Diseases

Skin Neoplasms

Skin Diseases

Howard H Bailey, MD

This is a double blind, placebo controlled study of 52 patients who are at least one-year post-solid organ transplant. Subjects will receive either 12 months of DFMO or a placebo. The specific aims are to determine if DFMO at 500 mg daily will be well tolerated for 12 months and not affect organ transplant viability; will inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC) in skin biopsies by approximately 50% for the 12 months of therapy; and will be able to decrease polyamine levels in skin biopsies for the 12 months of treatment.

Difluoromethylornithine (DFMO) Chemoprevention of Skin Cancer in Organ Transplant Recipients

Phase 2b Difluoromethylornithine (DFMO) Chemoprevention of Skin Cancer in Organ Transplant Recipients (OTR)

National Cancer Institute (NCI)

University of Wisconsin, Madison

Rare Diseases

Medulloblastoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID on each day of study.

DFMO (difluoromethylornithine is an inhibitor of ornithine decarboxylase (ODC) designated chemically as 2-(difluoromethyl)-DL-ornithine monohydrochloride monohydrate.

The dosage form to be used in this study is provided as a convex tablet containing 192 mg eflornithine (equivalent to 250 mg of eflornithine HCl, monohydrate). The tablets are packaged and sealed in opaque white HDPE bottles, and each bottle contains 100 tablets. The DMFO tablets are supplied by USWorldMeds (USWM).

The tablets are to be stored at room temperature (20-250C).

Genevieve Bergendahl, MSN

Susan Hall

Kevin Bielamowicz, MD

Group Contact

Jennifer Michlitsch, MD

Franchesca Ramirez

William Roberts, MD

Nicole McCracken

Michael Isakoff, MD

Michelle Pellet

Amy Smith, MD

Jennifer Manns

Don Eslin, MD

Brittany Fuller

Tom Badgett, MD

Jennifer Miller

Michael A Huang, MD

Huang A Michael, MD

Nicole Harvey

Kevin Ginn, MD

Gina Martin, RN

William Ferguson, MD

Sherri Mayans

Derek Hanson, MD

Jontyce Green

Thomas Russell, MD

Suzanne Treadway

Valerie Brown, MD

Shanta Salzar, MD

Jaqueline Kraveka, MD

Rhea Robinson, RN

Virginia Harrod, MD

Difluoromethylornithine (DFMO) will be used in an open label, multicenter, study as Maintenance Therapy for Molecular High Risk/Very High Risk and Relapsed/Refractory Medulloblastoma.

In this study subjects will receive 730 Days of oral difluoromethylornithine (DFMO) at a dose of 2500 mg/m2 BID on each day of study.

Subjects will be evaluated in 3 Cohorts:

Cohort 1: Molecular High Risk Medulloblastoma Cohort 2: Molecular Very High Risk Medulloblastoma Cohort 3: Relapsed/Refractory Medulloblastoma

A total of 118 subjects across all cohorts will be enrolled to ensure that there will be 107 evaluable subjects (32-39 per cohort)

DFMO as Maintenance Therapy for Molecular High/Very High Risk and Relapsed Medulloblastoma

Phase II Trial of Eflornithine/DFMO as Maintenance Therapy for Molecular High Risk/Very High Risk and Relapsed/Refractory Medulloblastoma

o To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in preventing relapse in patients with molecular high risk and very high risk medulloblastoma, and relapsed/refractory medulloblastoma based upon the 2-year progression-free survival rate (PFS) compared to relevant historical controls.

o To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in patients with molecular high risk and very high risk medulloblastoma, and relapsed/refractory medulloblastoma based upon overall survival

To evaluate the efficacy of difluoromethylornithine (DFMO) as a single agent in patients with molecular high risk and very high risk medulloblastoma, and relapsed/refractory medulloblastoma based upon Response Rate for patients with non-bulky residual disease present.

To develop a complete safety and tolerability profile of difluoromethylornithine (DFMO) in pediatric and young adult subjects with medulloblastoma.

o To measure CSF penetration after DFMO administration in pediatric subjects with medulloblastoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Targeting ODC as an Immunotherapeutic Target in STK11 (LKB1) Pathway-Deficient NSCLC (DFMO)	NCT06219174	Non Small Cell ... Lung Cancer	Pembrolizumab Difluoromethylo...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Urinary Biomarker Study With Sulindac and Difluoromethylornithine	NCT01636128	Focus of Study:...	difluoromethylo... Sulindac	40 Years - 65 Years	Cancer Prevention Pharmaceuticals, Inc.
Difluoromethylornithine (DFMO) Chemoprevention of Skin Cancer in Organ Transplant Recipients	NCT00204789	Post-solid Orga... Skin Neoplasms	Difluoromethylo...	21 Years -	University of Wisconsin, Madison
DFMO as Maintenance Therapy for Molecular High/Very High Risk and Relapsed Medulloblastoma	NCT04696029	Medulloblastoma	Difluoromethylo...	- 21 Years	Milton S. Hershey Medical Center
Difluoromethylornithine (DFMO) Chemoprevention of Skin Cancer in Organ Transplant Recipients	NCT00204789	Post-solid Orga... Skin Neoplasms	Difluoromethylo...	21 Years -	University of Wisconsin, Madison
DFMO as Maintenance Therapy for Molecular High/Very High Risk and Relapsed Medulloblastoma	NCT04696029	Medulloblastoma	Difluoromethylo...	- 21 Years	Milton S. Hershey Medical Center
DFMO as Maintenance Therapy for Molecular High/Very High Risk and Relapsed Medulloblastoma	NCT04696029	Medulloblastoma	Difluoromethylo...	- 21 Years	Milton S. Hershey Medical Center

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