Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Dermatologic Agents

All Drugs and Chemicals

Micronutrients

Vitamins

Tretinoin

Vitamin A

Retinol palmitate

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Keratolytic Agents

Retinol

Arm A (No VESANOIDTherapy) will receive the standard of care treatment with ipilimumab only, receiving the standard 4 doses of either 3 or 10 mg/kg ipilimumab every 3 weeks.

Arm B (VESANOID Therapy) will receive the standard 4 doses of either 3 or 10 mg/kg ipilimumab every three weeks plus the supplemental treatment of 150 mg/m2 of VESANOID orally for 3 days surrounding each dose of ipilimumab (day -1, day 0, day +1) for a total of 12 days of VESANOID treatment.

All-trans retinoic acid (ATRA) is a vitamin A derivative that binds the retinoic acid receptor on MDSCs and differentiates immature monocytes into more mature dendritic cells (12). VESANOID is a standard treatment for patients with acute promyelocytic leukemia (APL).

VESANOID

Ipilimumab is current standard of care treatment for melanoma.

Martin McCarter, MD

The purpose of this study is to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients.

The successful treatment of melanoma with immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1) antibodies, has altered our thinking and approach to immunotherapy for solid tumors. Despite these advances, only a portion of patients experience a durable response suggesting that there is room for improvement via enhanced immunomodulatory approaches. Anti-CTLA-4 (Ipilimumab) significantly improves overall survival and achieves long-lasting complete responses in some melanoma patients, the number of patients that achieve durable clinical benefit is limited and could be improved by a combined immunomodulatory approach. The objectives of this study are to assess the safety and efficacy of combined treatment with Ipilimumab and all-trans retinoic acid (ATRA) in melanoma patients. We hypothesize that combined treatment with Ipilimumab and ATRA will improve patient responses, increase tumor antigen-specific T cell responses, and decrease immunosuppressive myeloid-derived suppressor cells (MDSCs) in melanoma patients compared to patients treated with Ipilimumab alone.

Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma

Safety and tolerability of ipilimumab and VESANOID combination therapy in advanced melanoma patients will be established using the Bayesian approach.

The frequency of circulating MDSCs will be measured by flow cytometry and calculated as a percentage of the total myeloid cell population. This outcome will be measured at the final study blood draw between 84 and 130 days following the first treatment.

MDSC suppressive function in peripheral blood will be measured through the activation and proliferation of T cells in the presence of isolated MDSCs. Functional assays will be performed to assess the ability of isolated MDSCs to suppress T-cell responses.

Changes in the frequency of tumor-specific T cell responses attributable to the addition of VESANOID to standard ipilimumab therapy will be determined by the frequency of Interferons (IFN)-gamma producing cells after stimulation with melanoma antigens.

Subjects will be followed for evidence of disease progression.

University of Colorado, Denver

Arm A (No VESANOIDTherapy) will receive the standard of care treatment with ipilimumab only, receiving the standard 4 doses of either 3 or 10 mg/kg ipilimumab every 3 weeks.

Ipilimumab: Ipilimumab is current standard of care treatment for melanoma.

Arm B (VESANOID Therapy) will receive the standard 4 doses of either 3 or 10 mg/kg ipilimumab every three weeks plus the supplemental treatment of 150 mg/m2 of VESANOID orally for 3 days surrounding each dose of ipilimumab (day -1, day 0, day +1) for a total of 12 days of VESANOID treatment.

VESANOID: All-trans retinoic acid (ATRA) is a vitamin A derivative that binds the retinoic acid receptor on MDSCs and differentiates immature monocytes into more mature dendritic cells (12). VESANOID is a standard treatment for patients with acute promyelocytic leukemia (APL).

Ipilimumab: Ipilimumab is current standard of care treatment for melanoma.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Martin McCarter

Number of Adverse Events

MDSC Frequency

MDSC Suppressive Function

Changes in the Frequency of Tumor-specific T Cell Responses

Unresectable Stage III and STAGE IV

Overall Study

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Anti-Infective Agents

Nivolumab

Antibodies

Immunoglobulins

Interferons

Nivolumab: 3mg/kg intravenously on day 1.

All-trans retinoic acid (Vesanoid) 45 mg/m2 on days 1-14. The dose of Vesanoid can be increased with addition of 15 mg/m2 in next course of treatment if there is no severe adverse effects. Therefore, the dose of Vesanoid could be 60 mg/m2 from the second course, 75 mg/m2 from the third course, till the maximal dose of 150 mg/m2 if patients tolerated the treatment. The decision of dose escalation is left to in-charge physician.

The treatment cycle will repeat every 2 weeks.

Nivolumab, an immune checkpoint inhibitors targeting PD-1, represents a popular treatment option for patients with cancers via immunological mechanism. However, previous studies using nivolumab alone in pancreatic cancer have failed.

Our previous basic studies revealed that all-trans retinoic acid repressed pancreatic adenocarcinoma cell growth and colony formation. All-trans retinoic acid represses ADAR1, a member of interferon-stimulated genes and a negative regulator of IFNs signaling. On the other hand, all-trans retinoic acid simultaneously increases PD-L1 expression for cancer cells to evade immune surveillance. Since combination of anti-PD1 antibody and all-trans retinoic acid may block self-regulating negative feedback loops of IFNs response, this therapeutic strategy may improve outcomes of pancreatic adenocarcinoma patients.

all trans retinoic acid

Li-Yuan Bai

This study is to examine the anticancer activity of the combination therapy with all-trans retinoic acid and nivolumab in patients with chemotherapy-refractory advanced or metastatic pancreatic adenocarcinoma.

Pancreatic cancer is an aggressive and lethal disease. Even two combination regimens, FOLFIRINOX and albumin-bound paclitaxel in combination with gemcitabine, are superior to gemcitabine alone as the first-line treatments, the prognosis of patients with locally advanced or metastatic pancreatic cancer remains poor, with a median overall survival of 8 to 11 months and an estimated 2-year survival of only 2%. Even more, there is currently no available treatment proven beneficial for patients who fail the second-line therapy with liposomal irinotecan in combination with 5-FU.

Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a popular treatment option for patients with some kinds of cancers, but previous studies in pancreatic cancer have failed. One critical challenge for immunotherapy in pancreatic cancer is to find efficient therapeutic approaches to reverse this "cold" tumor into a "hot" tumor. Our previous basic studies revealed that all-trans retinoic acid repressed pancreatic adenocarcinoma cell growth and colony formation. Set-to-set genetic analysis revealed that genes regulated by all-trans retinoic acid were predominantly involved in immune response including interleukin-6, tumor necrotic factor-α, IFNs signaling, and PD-L1. Furthermore, mice bearing pancreatic cancer treated with combination of anti-PD-1 and all-trans retinoic acid had a significantly longer survival compared to mice treated with anti-PD-1 or all-trans retinoic acid alone.

Based on the previous findings, we propose this pilot, compassionate use of combination therapy with all-trans retinoic acid and nivolumab for patients with locally advanced or metastatic pancreatic adenocarcinoma who are refractory to current available treatment. This study will also examine ADAR1 as a novel prognostic and predictive biomarker for pancreatic adenocarcinoma patients. This study will help to delineate the role of ADAR1 as a predictive biomarker for immunotherapy, all-trans retinoic acid as a suppressor of ADAR1, and most importantly, the combination of all-trans retinoic acid and nivolumab as an effective anticancer therapy for patients with pancreatic adenocarcinoma.

Nivolumab and All-trans Retinoic Acid for Pancreatic Cancer

Treatment With Nivolumab and All-trans Retinoic Acid for Patients With Refractory Pancreatic Cancer

The median duration of time from the time of registration until death

Overall response is evaluated using Response Evaluation Criteria in Solid Tumors criteria (RECIST 1.1). A participant is considered to have responded if either of the following outcomes is achieved:

1. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm
2. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

The median duration of time from the time of registration until disease progression or death. Disease progression is assessed using RECIST 1.1 criteria.

China Medical University Hospital

Blood and Lymph Conditions

Leukemia

Leukemia, Promyelocytic, Acute

Hematologic Diseases

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Acute Graft Versus Host Disease

Acute Promyelocytic Leukemia

Arsenic Trioxide

Daily oral NRX 195183 administration for 90 days to assess CR rate. Patients with CR may continue maintenance therapy after a 2-week drug holiday. Maintenance therapy will consist of two 3-month daily oral NRX 195183 administration separated by a 2-week drug holiday.

NRX 195183 Soft Gelatin Capsule

Nonna Snider, BS/BA

Linda Gero

Victoria Chua

The purpose of this study is to determine whether NRX 195183 is effective in the treatment of relapsed or refractory Acute Promyelocytic Leukemia

A common current therapeutic approach to APL uses oral ATRA and chemotherapy in induction and consolidation. This approach has significantly improved survival in newly diagnosed APL patients. However, approximately 30% of patients relapse. Recently, an approach involving the combination of oral ATRA and arsenic trioxide has been tested. The prognosis for relapsed patients is very poor. This study seeks to investigate NRX 195183 monotherapy in patients who have failed or are resistant to or are intolerant of any prior therapy.

Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia

Phase II Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia

NuRx Pharmaceuticals, Inc.

Roshantha A. Chandraratna, PhD, MBA, Chief Scientific Officer

This is a multicenter, phase II trial to study the efficacy of combined tretinoin and ATO in the treatment of newly diagnosed APL in an effort to reduce or eliminate the amount of standard chemotherapy required for long-term remission.

Tretinoin and Arsenic Trioxide

Jae Park, MD

The purpose of this study is to find what effects, good and/or bad, treatment with two drugs has on leukemia. The first medicine is tretinoin (also called all-trans retinoic acid, ATRA, or Vesanoid). It is an approved medicine that causes the leukemia cells in APL to mature. It is related to vitamin A. The second is arsenic trioxide (Trisenox). It is an approved medicine for APL that comes back after earlier treatment.

APL is most often treated with tretinoin and standard chemotherapy drugs. These chemotherapy drugs can cause infection and bleeding. They can also damage the heart and normal bone marrow cells. This can lead to a second leukemia years later.

In this study, the investigators are using tretinoin and arsenic trioxide together. Both drugs work to treat APL. They have been used together in only a limited number of people. The investigators want to use these drugs together to reduce the amount of standard chemotherapy and decrease side effects. The patient will receive standard chemotherapy with a drug called idarubicin only if they have a higher chance of the leukemia coming back or a higher risk of side effects.

Induction will consist of tretinoin 45 mg/m2 po daily (rounded up to the nearest 10mg) in two divided doses (25 mg/m2 in patients \<20 years of age) for 35 days and ATO 0.15 mg/kg IV daily for 35 doses given 5-7 days per week. The drugs will then be discontinued, and the patient will be followed until a clinical complete remission is achieved. Idarubicin 12 mg/m2 IV for 4 doses will be added during induction on day 2 if the presenting WBC is \>10,000/μl, or if the WBC increases to 5,000/μl on day 5, 10,000/μl on day 10, or 15,000/μl on day 15, because of the increased risk of the APL differentiation syndrome and relapse in these patients. Dexamethasone 10 mg twice daily with be given on days 1-14 of induction as prophylaxis for the APL differentiation syndrome. All patients will then receive four courses of consolidation with tretinoin 45 mg/m2 po daily (rounded up to the nearest 10mg) (25 mg/m2 in patients \<20 years of age) for 15 days and ATO 0.15 mg/kg IV for 25 doses.

Patients with high-risk disease or who received Idarubicin during Induction may receive intrathecal cytarabine as CNS prophylaxis given by the treating physician during consolidation, at the discretion of the site PI. High-risk patients will also receive maintenance therapy with additional courses of tretinoin and ATO every 3 months for 2 years. Each maintenance course will consist of tretinoin 45 mg/m2 po daily (25 mg/m2 in patients \<20 years of age) for 15 days and ATO 0.15 mg/kg IV for 10 doses. Disease status will be monitored with serial analyses of peripheral blood samples using RT-PCR for PML-RARα mRNA. Patients will be followed until relapse, death, loss to follow-up, or removal from study.

Induction therapy can be given as an inpatient or outpatient. Consolidation and maintenance treatments will be given as an outpatient. Consolidation may also be given at the patient's local institution. Intrathecal cytarabine treatments will be administered as an outpatient.

Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy

Phase II Study of Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy

after induction with combined tretinoin and ATO (along with idarubicin in patients with high-risk disease or who develop leukocytosis) in APL.

after induction with tretinoin and ATO (with idarubicin in patients with high-risk disease or who develop leukocytosis).

after each course of postremission therapy.

including the early death rate (within 30 days), the incidence of APL differentiation syndrome, the number and length of hospitalizations, the incidence of secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), and the effects of treatment on left ventricular ejection fraction (LVEF) Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 will be tabulated.

with combined tretinoin and ATO using serial immunophenotyping studies of peripheral blood

by ATRA (Tretinoin) and ATO (Arsenic Trioxide). Bone marrow samples will be analyzed at baseline and at the time of clinical CR for telomerase activity, telomere length and TERT expression

Northwestern University

New York Presbyterian Hospital

University of Southern California

Princess Margaret Hospital, Canada

National Heart, Lung, and Blood Institute (NHLBI)

Memorial Sloan Kettering Cancer Center

This is a multicenter, phase II trial to study the efficacy of combined tretinoin and ATO in the treatment of newly diagnosed APL in an effort to reduce or eliminate the amount of standard chemotherapy required for long-term remission.

Tretinoin and Arsenic Trioxide: See Detailed Description

Ethnicity (NIH/OMB)

Dr. Jae Park, MD

To Determine the Rate of Molecular Remission

Participants Who Experienced a Complete Remission

To Determine the Proportion of Patients in Molecular Remission

To Determine the Disease-free and Event-free Survival of Patients

To Determine the Toxicity of This Treatment Program

To Characterize the Differentiation of APL Cells During Treatment

Explore the in Vivo Induction of Telomerase-dependent Cell Death

Symptoms and General Pathology

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

Azacitidine

Decitabine

Valproic Acid

Antimetabolites

Enzyme Inhibitors

Neurotransmitter Agents

Daily for 7 days, Valproic acid (VPA) starting dose 75 mg/m\^2 subcutaneously in combination with 5-azacytidine (5-aza) 50 mg/kg orally; and all-trans retinoic acid (ATRA) 45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3.

Start at 75 mg/m\^2 subcutaneously daily for 7 days.

5-Azacytidine (5-aza)

50 mg/kg daily by mouth for 7 days, same days as 5-aza.

45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3 of the administration of 5-aza and VPA.

All-Trans Retinoic Acid (ATRA)

Guillermo Garcia-Manero, MD

5-aza is a chemotherapy drug with activity in leukemia and myelodysplastic syndromes (MDS). Researchers hope that valproic acid (VPA) and all-trans retinoic acid (ATRA)will increase the effects of 5-aza. The goal of this clinical research study is to find the highest safe dose of valproic acid (VPA) that can be given in combination with 5-azacytidine (5-aza) and all-trans retinoic acid (ATRA) in the treatment of AML and MDS. The safety and effectiveness of this combination therapy will also be studied.

Additional blood and bone marrow samples will be requested. These samples will be used to evaluate the effect of the treatment on leukemic cells. In addition, any leftover blood and bone marrow samples that are collected at the start of the study and during the regularly scheduled evaluations to be sent for research studies. The research studies will examine changes in the blood and bone marrow cells that might help explain the causes of leukemia and MDS and how the combination of 5-aza, VPA, and ATRA works.

Recent studies have shown synergy between demethylating agents and histone deacetylase inhibitors. In my laboratory, we have developed in vitro models using HL-60 and MOLT4 leukemic cells to study the effects of the combination of decitabine (a 5-azacytidine analogue) and valproic acid. Valproic acid is an antiepileptic agent with histone deacetylase inhibitory capacity. These results indicate that the addition of valproic acid to decitabine has an additive effect on growth inhibition, induction of apoptosis, induction of p57KIP2 and p21CIP1 expression independent of cell cycle arrest. These results were dependent on the dose and duration of treatment but not on the sequence used. Based on this data, we developed a phase I/II study of the combination of decitabine and valproic acid (2003-0314) in patients with leukemia that has shown that valproic acid can be safely administered up to doses of 50 mg/kg orally for 10 days in combination with decitabine, and that this combination has significant activity in patients with relapsed/refractory AML and MDS. All-trans retinoic acid (ATRA) is a biological agent that has been shown to induce cell differentiation in leukemia cell lines and has significant clinical activity in acute promyelocytic leukemia with minimal toxicity. In vitro, the combination of ATRA with either a hypomethylating agent or a histone deacetylase inhibitor has been shown to restore ATRA sensitivity in resistant cells. More recently, a German group has reported that the combination of valproic acid and ATRA has activity in patients with MDS and an excellent toxicity profile. 5-azacytidine is a nucleoside analogue with hypomethylating activity that has been shown in a randomized study to benefit patients with MDS, including an improvement in quality of life. Based on this data, this agent was recently approved by the FDA for its use in patients with MDS, and has become the first line agent for patients with MDS that required therapy.

The objectives of the clinical trial are the following:

* To determine the maximal tolerated dose of valproic acid (VPA) in combination with 5-azacytidine (5-aza) and all-trans retinoic acid.
* To determine the clinical activity of the combination of 5-azacytidine, valproic acid and all-trans retinoic acid in patients with AML and MDS.
* To determine the in vivo molecular and biological effects of this combination. These will include analysis of changes in Deoxyribonucleic acid (DNA) methylation, histone modifications, and gene expression.

Phase II 5-Azacytidine Plus VPA Plus ATRA

Phase II Study of the Combination of 5-azacytidine With Valproic Acid and All-trans Retinoic Acid in Patients With High Risk Myelodysplastic Syndrome and Acute Myelogenous Leukemia

Clinical activity of combination defined as: Complete Response (CR), bone marrow with 5% or fewer blasts and peripheral blood count with an absolute neutrophil count of 10\^9/L or more and platelet count of 100x10\^9 or more; Complete response without platelets (CRp), a complete response except for a platelet count less than 100x10\^9 and transfusion independent; and Bone Marrow (BM) Response, bone marrow blast of 5% or less but without meeting the peripheral blood count criteria for (CR) or (CRp).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ipilimumab and All-Trans Retinoic Acid Combination Treatment of Advanced Melanoma	NCT02403778	Melanoma	VESANOID Ipilimumab	18 Years - 89 Years	University of Colorado, Denver
Nivolumab and All-trans Retinoic Acid for Pancreatic Cancer	NCT05482451	Effect of Drug	Nivolumab all trans retin...	20 Years - 100 Years	China Medical University Hospital
Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia	NCT00675870	Acute Promyeloc...	NRX 195183 Soft...	18 Years -	NuRx Pharmaceuticals, Inc.
Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy	NCT01404949	Acute Promyeloc...	Tretinoin and A...	18 Years -	Memorial Sloan Kettering Cancer Center
Phase II 5-Azacytidine Plus VPA Plus ATRA	NCT00326170	Myelodysplastic... Acute Myelogeno...	5-Azacytidine (... Valproic Acid All-Trans Retin...	3 Years -	M.D. Anderson Cancer Center
Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia	NCT00675870	Acute Promyeloc...	NRX 195183 Soft...	18 Years -	NuRx Pharmaceuticals, Inc.
Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy	NCT01404949	Acute Promyeloc...	Tretinoin and A...	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for vesanoid

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

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