Neoplasms

All Conditions

Rare Diseases

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Analgesics

Anti-Infective Agents

Amino Acids

Cyclophosphamide

Topotecan

Celecoxib

Eflornithine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Enzyme Inhibitors

Topoisomerase I Inhibitors

Antiprotozoal Agents

Antiparasitic Agents

Ornithine

Reconstituted DFMO powder by mouth for 14 days and celecoxib capsule by mouth daily in each cycle. Cyclophosphamide and Topotecan IV on days 8-12 in cycle 1 and days 1-5 of cycles 2-17. Patients may continue for up to 17 cycles as long as therapy is tolerated (no DLT) and disease progression does not occur (SD or better). \*Cycle 1 will include a 7 day lead-in with DFMO and celecoxib to deplete tumor polyamines.

DFMO

Michael Hogarty, MD

This study will combine an oral drug called DFMO with celecoxib (also oral) and two IV chemotherapy medicines called cyclophosphamide and topotecan.

* To find the highest dose of DFMO that can be given with celecoxib, cyclophosphamide and topotecan without causing severe side effects.
* To find out the side effects seen by giving DFMO at different dose levels with celecoxib, cyclophosphamide and topotecan.
* To measure the levels of DFMO in the blood at different dose levels.
* To determine if your tumor gets smaller after treatment with DFMO, celecoxib, cyclophosphamide and topotecan.
* To determine if specific gene changes in you or your tumor makes you more prone to side effects or affects your tumor's response to the combination of DFMO, celecoxib, cyclophosphamide and topotecan.
* To determine if the amount of normal chemicals in your body called polyamines go down in response to DFMO, celecoxib, cyclophosphamide and topotecan, and whether you are more likely to have a good response to the treatment if they do.

N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan

N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan for Patients With Relapsed or Refractory Neuroblastoma

The standard 3+3 design for dose escalation will be utilized. 3-6 patients will enroll at each of 4 dose levels, but enrollment to a dosing cohort will cease after observation of DLTs in 2 or more patients. A minimum of 2 to a maximum of 24 patients will be enrolled assuming all 4 dose levels require 6 patients before an MTD is determined. A total of 12 patients may be enrolled at the study defined MTD (including those used to define the MTD) to provide additional adverse event data for safety evaluation.

National Cancer Institute (NCI)

New Approaches to Neuroblastoma Therapy Consortium

Sulindac

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

Dermatologic Agents

Immunomodulating Agents

Dasatinib

Isotretinoin

Sorafenib

Dinutuximab

Vorinostat

Ceritinib

Protein Kinase Inhibitors

Tyrosine Kinase Inhibitors

Histone Deacetylase Inhibitors

Tyrosine

One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin. At the end of immunotherapy, DFMO will be given to all subjects BID for 730 days.

One of the following drugs will be chosen for each subject based on molecular guided results: ceritinib, dasatinib, sorafenib or vorinostat. This will be followed standard immunotherapy with Dinutuximab/GM-CSF/IL-2 and isotretinoin PLUS 1000mg/m2 BID of DFMO. At the end of immunotherapy, all subjects will go on to receive DFMO BID for 730 days.

One of the following drugs will be chosen for each subject based on molecular guided results: Ceritinib, dasatinib, sorafenib or vorinostat. This will be followed by consolidation, immunotherapy +/- DFMO, and then all subjects will receive DFMO for 2 years as maintenance.

dasatinib

sorafenib

vorinostat

DFMO will be given to Arm B during immunotherapy and then for 2 years as maintenance to all subjects completing immunotherapy.

Genevieve Bergendahl, MSN

Bridget Tate

Elizabeth Alva, MD

Susan Hall

Kevin Bielamowicz, MD

Group Contact

Jennifer Michlitsch, MD

Franchesca Ramirez

William Roberts, MD

Nicole McCracken

Michael Isakoff, MD

Jose RodriguezAlonso

Guillermo De Angulo, MD

Michelle Pellet

Amy Smith, MD

Jennifer Manns, RN

Don Eslin, MD

Kimberly Gray

Coleen McDonough, MD

Andrea Siu, MPH

Randal Wada, MD

Callie Wiskus

Martha Pachecho, MD

Jennifer Ward

Rebecca McFall, MD

Jennifer Miller

Ashok Raj, MD

Mary Beth Readwin

David Hoogstra, MD

Nel Siemsen

Jawhar Rawwas, MD

Nicole Harvey

Kevin Ginn, MD

Gina Martin, RN

William Ferguson, MD

Sherri Mayans

Derek Hanson, MD

Jontyce Green

Thomas Russell, MD

Aaron White

Jason Glover, MD

Suzanne Treadway

Valerie Brown, MD

Shanta Salzar, MD

Jaqueline Kraveka, MD

Rhea Robinson

Virginia Harrod, MD

Caitlyn Ambrose

Tanya Watt, MD

Sabrina Wigginton

Eric Lowe, MD

Guillaume Leblanc

Pierre Tiera, MD

Giselle Sholler, MD

A prospective open label, multicenter study to evaluate the feasibility and acute toxicity of using molecularly guided therapy in combination with standard therapy followed by a Randomized Controlled Trial of standard immunotherapy with or without DFMO followed by DFMO maintenance for Subjects with Newly Diagnosed High-Risk Neuroblastoma.

Pediatric Precision Laboratory Advanced Neuroblastoma Therapy

A Study Using Molecular Guided Therapy With Induction Chemotherapy Followed by a Randomized Controlled Trial of Standard Immunotherapy With or Without DFMO Followed by DFMO Maintenance for Subjects With Newly Diagnosed High-Risk Neuroblastoma

To measure the response of treatments chosen based on:

• Event free survival (EFS)

At completion of the induction therapy, the investigators will determine feasibility of adding molecularly guided targeted therapy to standard of care chemotherapy. Feasibility will be defined as:

1. Subject has a targeted agent identified
2. Receives 75% of dosing of medications while on study protocol during cycles 3-6
3. Subject is not removed from study due to targeted agent drug related toxicity.

To measure the response of treatments chosen based on:

* Overall response rate (ORR) after induction therapy
* Overall survival (OS)

To measure the response of treatments chosen based on:

• Overall response rate (ORR) after induction therapy

To compare toxicity effects of difluoromethylornithine (DFMO) in combination with Dinutuximab/GM-CSF/IL-2 and isotretinoin versus Dinutuximab/GM-CSF/IL-2 and isotretinoin alone.

To compare level of pain medicine needed during immunotherapy in patients receiving difluoromethylornithine (DFMO) in combination with Dinutuximab/GM-CSF/IL-2 and Isotretinoin versus those receiving Dinutuximab/GM-CSF/IL-2 and isotretinoin alone.

Dell, Inc.

Beat NB Cancer Foundation

K C Pharmaceuticals Inc.

Team Parker for Life

Giselle Sholler

Beat Childhood Cancer Chair

Etoposide

Etoposide phosphate

Escalating doses of DFMO in a 3 +3 cohort design.

DFMO at current cohort Dose Level orally each day for 21 day cycles

Dose level 1: 500 mg/m2 PO BID Dose level 2: 750 mg/m2 PO BID Dose level 3:1000 mg/m2 PO BID Dose level 4:1500 mg/m2 PO BID

Starting with Cycle 2, etoposide will be given at 50mg/m2/dose PO daily for the first 14 days of each 21 day cycle. Capsules will be rounded to closest 50 mg.

The purpose of this research study is to evaluate a new investigational drug to treat neuroblastoma. This study drug is called DFMO. The objectives of this study will be to monitor for safety and to find a maximum tolerated dose in this population. A secondary objective will be to look at efficacy of DFMO.

The safety of the proposed dosing regimen in this trial will be tested by an on-going risk/benefit assessment during the study. A patient benefiting from treatment, not progressing on therapy, and in the absence of any safety issues associated with DFMO and/or etoposide may continue on treatment with the expectation that there will be an overall clinical benefit.

The procedures involved in this study include Medical history, Physical exam, Vital signs (blood pressure, pulse, temperature), Blood tests, Urine tests, MRI or CT scan of the tumor(s), MIBG scans, and Bone marrow aspirations. All of these tests and procedures are considered standard of care for this population. Drug administration is also part of this protocol, including an investigational new drug called DFMO, and later combined with an already approved drug, etoposide.

The proposed dosing regimen is an oral dose of DFMO two times a day for each day while on study. There will be 5 cycles. Each cycle will be 21 days in length. The first cycle will be DFMO alone. In the second cycle etoposide will be added in and will be given orally once a day for the first 14 days of each cycle (cycles 2-5).

Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide

A Phase I Trial for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide

To determine the safety, tolerability and maximum tolerated dose (MTD) of DFMO as a single agent and in combination with etoposide in pediatric and young adult patients with refractory or recurrent neuroblastoma

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

University of Hawaii

DFMO: Escalating doses of DFMO in a 3 +3 cohort design.

DFMO at current cohort Dose Level orally each day for 21 day cycles

Dose level 1: 500 mg/m2 PO BID Dose level 2: 750 mg/m2 PO BID Dose level 3:1000 mg/m2 PO BID Dose level 4:1500 mg/m2 PO BID

Etoposide: Starting with Cycle 2, etoposide will be given at 50mg/m2/dose PO daily for the first 14 days of each 21 day cycle. Capsules will be rounded to closest 50 mg.

DFMO and Etoposide

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

DFMO: Escalating doses of DFMO in a 3 +3 cohort design.

DFMO at current cohort Dose Level orally each day for 21 day cycles

Dose level 1: 500 mg/m2 PO BID

Etoposide: Starting with Cycle 2, etoposide will be given at 50mg/m2/dose PO daily for the first 14 days of each 21 day cycle. Capsules will be rounded to closest 50 mg.

Dose Level 1: 500 mg/m2 PO BID

DFMO: Escalating doses of DFMO in a 3 +3 cohort design.

DFMO at current cohort Dose Level orally each day for 21 day cycles

Dose level 2: 750 mg/m2 PO BID

Etoposide: Starting with Cycle 2, etoposide will be given at 50mg/m2/dose PO daily for the first 14 days of each 21 day cycle. Capsules will be rounded to closest 50 mg.

Dose Level 2: 750 mg/m2 PO BID

DFMO: Escalating doses of DFMO in a 3 +3 cohort design.

DFMO at current cohort Dose Level orally each day for 21 day cycles

Dose level 3:1000 mg/m2 PO BID

Etoposide: Starting with Cycle 2, etoposide will be given at 50mg/m2/dose PO daily for the first 14 days of each 21 day cycle. Capsules will be rounded to closest 50 mg.

Dose Level 3:1000 mg/m2 PO BID

DFMO: Escalating doses of DFMO in a 3 +3 cohort design.

DFMO at current cohort Dose Level orally each day for 21 day cycles

Dose level 4:1500 mg/m2 PO BID

Etoposide: Starting with Cycle 2, etoposide will be given at 50mg/m2/dose PO daily for the first 14 days of each 21 day cycle. Capsules will be rounded to closest 50 mg.

Dose Level 4:1500 mg/m2 PO BID

Number of Participants With Adverse Events as a Measure of Safety and Tolerability

18 subjects out of the 21 enrolled were evaluable. 3 subjects did not make it to an evaluable time point.

Progression Free Survival (PFS)

Number of Patients With an Overall Response Rate (ORR) of PR or CR

Tmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.

Cmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.

AUC of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.

Overall Study

Carcinoma

Lysine

Dose escalation of AMXT1501 with a fixed low dose of DFMO will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be 80 mg (2 capsules); each capsule contains 40 mg of active drug. The dose will be given orally, once daily, fasted state alone for 14 days, and starting on Day 15 AMXT 1501 80 mg given in combination with fixed low-dose oral DFMO at 250mg 2x per day (BID), for an additional 14 days; for a total 28 days of treatment per cycle. Cycle 2 includes AMXT1501 + DFMO that will be administered for 28 days. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of AMXT1501 alone will increase per Part 1 cohort.

Dose escalation of DFMO with the Part 1 AMXT1501 RP2D fixed dose will follow a 3 + 3 dose escalation design.

The AMXT 1501 starting dose administered in the first cohort will be one level below the AMXT 1501 Part 1 RP2D with 500 mg DFMO BID. The morning dose will be given orally of both AMXT1501 and DFMO, in a fasted state. The evening dose of DFMO alone will be given prior to bed-time for 28 days per cycle. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of DFMO alone will increase per Part 2 cohort.

The expansion cohort will include up to 14 evaluable patients at a proposed RP2D level of AMXT1501 and DFMO defined by Part 2 to further characterize safety at proposed RP2D dose level with repeat dosing, and characterize early anti-tumor activity.

AMXT 1501 dicaprate is D-lys(palmitoyl)-spermine dicaprate salt in 40 mg or 200 mg (free base content) enterically-coated capsules

AMXT1501

DFMO is DL-2-(difluoromethyl) ornithine monohydrochloride monohydrate 250 mg in hard gelatin capsules

Nicole Gallegos, BS, MBA

Jackie Walling, MBChB PhD

A Phase 1 study will be conducted to establish safety and dose level of AMXT 1501 dicaprate alone, and in combination with DFMO, in cancer patients.

The objective of this study is to determine the safety and tolerability of oral AMXT 1501 dicaprate (AMXT1501) in combination with DFMO in patients with advanced solid tumors. Secondary objectives include characterization of plasma pharmacokinetics (PK) of AMXT 1501 as well as pharmacodynamic (PD) assessment of the impact of AMXT 1501 in combination with DFMO on polyamine uptake by circulating lymphocytes (blood cells).

To these aims, the study will evaluate the safety, PK and PD profiles of orally-administered AMXT 1501 and DFMO. Approximately, 52 patients will be enrolled to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMXT 1501 and DFMO in combination. The MTD is defined as the highest dose level below at which dose escalation is stopped.

Oral AMXT 1501 Dicaprate in Combination With DFMO

Phase I Dose-Finding, Safety Study of Oral AMXT 1501 Dicaprate and Difluoromethylornithine (DFMO) in Patients With Advanced Solid Tumors

To evaluate the effect AMXT1501 in combination therapy with DFMO on pharmacodynamic (PD) biomarker of polyamine uptake

To evaluate dose-limiting toxicities (DLTs) of AMXT 1501 in combination with DFMO, in patients with advanced cancer and to establish a recommended Phase 2 dose (RP2D)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan	NCT02030964	Neuroblastoma	DFMO Celecoxib Cyclophosphamid... Topotecan	2 Years - 30 Years	New Approaches to Neuroblastoma Therapy Consortium
Urinary Biomarker Study With Sulindac and Difluoromethylornithine	NCT01636128	Focus of Study:...	difluoromethylo... Sulindac	40 Years - 65 Years	Cancer Prevention Pharmaceuticals, Inc.
Pediatric Precision Laboratory Advanced Neuroblastoma Therapy	NCT02559778	Neuroblastoma	Ceritinib dasatinib sorafenib vorinostat DFMO	- 22 Years	Milton S. Hershey Medical Center
Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide	NCT01059071	Neuroblastoma	DFMO Etoposide	-	Milton S. Hershey Medical Center
Oral AMXT 1501 Dicaprate in Combination With DFMO	NCT03536728	Cancer Solid Tumor Solid Carcinoma Advanced Cancer	AMXT1501 DFMO	12 Years -	Aminex Therapeutics, Inc.
Study of Difluoromethylornithine (DFMO) in Combination With Bortezomib for Relapsed or Refractory Neuroblastoma	NCT02139397	Neuroblastoma R...	DFMO Bortezomib	- 21 Years	Milton S. Hershey Medical Center
Preventative Trial of Difluoromethylornithine (DFMO) in High Risk Patients With Neuroblastoma That is in Remission	NCT02395666	Neuroblastoma	DFMO	- 21 Years	Milton S. Hershey Medical Center
Oral AMXT 1501 Dicaprate in Combination With DFMO	NCT03536728	Cancer Solid Tumor Solid Carcinoma Advanced Cancer	AMXT1501 DFMO	12 Years -	Aminex Therapeutics, Inc.
Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide	NCT01059071	Neuroblastoma	DFMO Etoposide	-	Milton S. Hershey Medical Center
Difluoromethylornithine and High Dose Testosterone With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer	NCT06059118	Prostate Cancer	DFMO testosterone cy... Luteinizing hor... Enzalutamide	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan	NCT02030964	Neuroblastoma	DFMO Celecoxib Cyclophosphamid... Topotecan	2 Years - 30 Years	New Approaches to Neuroblastoma Therapy Consortium

Spots Global Cancer Trial Database for dfmo

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

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