Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Atezolizumab 840mg IV every 2 weeks for 2 doses prior to surgery and 4 doses after surgery.

Atezolizumab 840mg IV every 2 weeks for 2 doses prior to surgery and 4 doses after surgery in combination with PEGPH20 3ug/kg IV twice weekly for 3 weeks prior to surgery and once weekly for 3 weeks (of 28 day cycle) for two cycles after surgery.

840mg IV every 2 weeks for 2 doses prior to surgery and 4 doses after surgery.

PEGPH20 3ug/kg IV twice weekly for 3 weeks prior to surgery and once weekly for 3 weeks (of 28 day cycle) for two cycles after surgery.

PEGPH20

Gulam Manji, MD, PhD

The purpose of this study is to determine if study treatment with atezolizumab and PEGPH20 given before and after surgery, followed by chemotherapy is safe and if it can further increase the immune response against the tumor rather than increase the chance of cure.

Presently, surgical resection offers the only therapeutic means of cure. However only 15%-20% of patients are found to have resectable disease at time of initial diagnosis. Of the patients who undergo curative surgery, most will relapse and eventually succumb to the disease. 5-year survival rates for node-negative and -positive disease at time of pancreatic duodenectomy are 25%-30% and 10%, respectively.

Although early phase trials have not offered great success in the metastatic setting for patients with pancreas adenocarcinoma (PDA), interim analysis of a multicenter, phase 1 trial with durvalumab presented at European Society for Medical Oncology (ESMO) indicated a disease control rate of 21%. As mentioned previously, PD-L1 expression correlates with poor prognosis and decreased CD4+ and CD8+ T cell infiltration within the tumor. Targeting PD-L1 in the micrometastatic setting (resectable disease), when robust mature immunosuppressive pathways may not have yet formed, may be the optimum time to investigate anti-PD-L1 therapy. This arm of the study aims to test if atezolizumab is able to modulate CD8+ T-cell infiltration compared to historical matched controls. As a secondary endpoint we will also evaluate how clinical outcomes compare to matched historical controls.

Neoplastic, immune, and stromal cells within PDA reside in a highly dense desmoplastic environment composed of an extracellular matrix of which hyaluronidase (HA) is an abundant component. HA is a linear glycosaminoglycan and an integral component of not only PDA tumors, but has also been shown to accumulate in many solid tumors and is associated with a poor prognosis and increased immunosuppression. In a preclinical autochthonous mouse model of PDA, Sunil Hingorani's group demonstrated that the interstitial fluid pressures were unusually high within tumors that exhibited a high HA content. Furthermore, high HA tumors contained low vascularity, which compromised delivery of chemotherapeutic agents, such as gemcitabine. Mice treated with hyaluronidase resulted in decreased HA content and microvasculature re-expansion within tumors which led to a survival benefit. These preclinical studies led to early phase clinical studies in metastatic PDA where addition of PEGPH20 to gemcitabine and nab-paclitaxel (GA) in a randomized phase 2 study demonstrated a survival benefit in patients with HA-high tumors. The objective response rate for patients who were treated with a combination of PEGPH20 and GA compared to GA alone was 45% versus 31%, respectively, and the median overall survival was 11.5 versus 8.5 months, respectively (hazard ratio (HR), 0.96; 95% Confidence Interval (CI), 0.57 to 1.61). A large phase 3 randomized clinical trial in the high HA stage IV PDA population in the first line setting is ongoing.

PDA likely invokes multiple immune evading mechanisms which result in its aggressive behavior; it is expected that multiple agents will likely be needed to develop effective therapies. One such rationale is the combination of PEGPH20 and immune checkpoint blockade to allow increased cytotoxic T-cell infiltration by increasing vascular permeability and decreasing interstitial pressure. In a breast cancer preclinical model, PEGPH20 resulted in an increase accumulation of CD8+ tumor-infiltrating lymphocytes (TIL) by 176% (p=0.0025) and improved tumor growth inhibition by 38% relative to anti-PD-L1 alone (86% vs 62.4%, p=0.0024). Other preclinical studies are also demonstrating increased CD8+ T-cell infiltration with addition of PEGPH20 and improved tumor control in combination with immune checkpoint blockade. These and other preclinical studies suggest that this combination is worth pursuing in patients with resectable PDA. The combination is hoped to increase CD8+ T-cell infiltration within the primary tumor for improved immune mediated cytotoxicity and decreased interstitial pressure to allow improved surgical resections. Hypothetically, the combination should also be effective in foci of micrometastasis, where the tumor microenvironment (TME) may not be as mature.

Identified risks for PEGPH20 include musculoskeletal events (MSEs), infusion-related reactions (IRRs), and thromboembolic (TE) events.

Randomized phase 2 trial for a total of 20 patients per cohort

Study Evaluating NEOadjuvant Immunotherapy in Resectable PANCreatic Ductal Adenocarcinoma

A Phase 2, Open-Label, Multicenter, Randomized Study Evaluating NEOadjuvant Immunotherapy Based Combinations in Patients With Resectable PANCreatic Ductal Adenocarcinoma

The change in number of intratumoral CD8+ T-cells the at time of surgery between treatment arm(s) compared to the atezolizumab arm. The CD8+ T-cell count within the tumor with neoadjuvant atezolizumab vs atezolizumab + PEGPH20 at the time of surgery will be reported using means and standard deviations by group and will be compared using a twosample T-test. If the data are not normally distributed, non-parametric models such as the Wilcoxon Rank Sum test will be used. Moreover, the distribution of CD8+ T-cell count by treatment arm will be assessed using box plots, histograms, and q-q plots.

To estimate the 18-month survival rate in patients treated with atezolizumab vs atezolizumab + PEGPH20 followed by surgery and adjuvant therapy.

To estimate the overall survival in patients treated with atezolizumab vs atezolizumab + PEGPH20 followed by surgery and adjuvant therapy.

To determine the R0 resection rates with atezolizumab vs atezolizumab + PEGPH20 administered in the neoadjuvant setting. R0 resection rate is defined by the proportion of patients in whom an R0 resection was achieved during surgery. R0 resection is defined by complete removal of macroscopic tumor which contains negative microscopic surgical margins. The R0 resection rate will be estimated by the number of patients in whom R0 resection was performed divided by total number of patients in each study arm. The R0 resection rate will be reported along with the exact 95% confidence interval. The investigators will compare the R0 resection rates using Fisher's exact test.

To determine the safety profile with atezolizumab vs atezolizumab + PEGPH20 or other therapies followed by surgery and adjuvant therapy. The frequency and count of grade 3 or higher adverse events will be reported by treatment group. The maximum grade for each type of adverse event will also be reported.

Genentech, Inc.

Halozyme Therapeutics

Gulam Manji

Assistant Professor of Medicine at Columbia University Medical Center

One participant enrolled into the study. That participant was determined to be a screen failure. Data was not collected and therefore there is no data to analyze.

Atezolizumab 840mg IV every 2 weeks for 2 doses prior to surgery and 4 doses after surgery.

Atezolizumab: 840mg IV every 2 weeks for 2 doses prior to surgery and 4 doses after surgery.

Atezolizumab 840mg IV every 2 weeks for 2 doses prior to surgery and 4 doses after surgery in combination with PEGPH20 3ug/kg IV twice weekly for 3 weeks prior to surgery and once weekly for 3 weeks (of 28 day cycle) for two cycles after surgery.

Atezolizumab: 840mg IV every 2 weeks for 2 doses prior to surgery and 4 doses after surgery.

PEGPH20: PEGPH20 3ug/kg IV twice weekly for 3 weeks prior to surgery and once weekly for 3 weeks (of 28 day cycle) for two cycles after surgery.

Atezolizumab in Combination With PEGPH20

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Study-Specific Baseline Measure

Change in the Number of CD8+ T Cells Within the Tumor

18-Month Survival Rate

Overall Survival

One participant enrolled in the study. That participant was determined to be a screen failure. Data was not collected and therefore there is no data to analyze.

R0 Resection Rate

Incidence of Treatment-Emergent Adverse Events

Overall Study

Blood and Lymph Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Central Nervous System Depressants

Other Dietary Supplements

Benzocaine

Lintuzumab

Tannic Acid

Subjects with AML will receive Ac-lintuzumab.

225Ac-lintuzumab will administered at 4 dose levels: 0.25, 0.5, 0.75 or 1 µCi/kg intravenously (IV) over 30 ± 10 minutes. The starting dose will be 0.5 µCi/kg. A dose of 0.25 µCi/kg will be studied only if 0.5 µCi/kg is determined to exceed the MTD. The lintuzumab dose will be adjusted to maintain a specific activity of 0.16 µCi/µg

Ac-Lintuzumab

Joseph Jurcic, MD

The purpose of this study is to see what dose of 225Ac-lintuzumab is safest to give to acute myeloid leukemia (AML) patients who are in remission but still have minimal residual disease (MRD). About 12 subjects will be asked to take part in this phase 1, 3+3 dose-escalation study. In addition to confirming the safety profile of postremission therapy with 225Ac-lintuzumab, preliminary evidence of efficacy will be assessed by estimating progression-free survival (PFS) and overall survival (OS), and serially evaluating for MRD using cytogenetics, fluorescence in situ hybridization (FISH), or flow cytometric assays, as applicable.

Therapy with α particle-emitting constructs of the anti-CD33 monoclonal antibody lintuzumab has demonstrated significant tumor effects in AML. Because therapy is selectively targeted to leukemic blasts, it has the potential advantage of less extramedullary toxicity than conventional systemic agents. Moreover, the unique radiobiological features of α particle emissions may permit more efficient tumor cell kill with greater specificity than treatment with β particle-emitting radioisotopes. Objective responses in AML following treatment with 225Ac-lintuzumab have been seen in cytoreduced disease, either following chemotherapy or using a fractionated dosing scheme.

The presence of MRD detectable by cytogenetic techniques and flow cytometric assays indicates a high risk of relapse for AML patients, despite achieving a clinical complete remission. The high linear energy and short range of α emissions make them ideally suited to eradicate MRD, as suggested by the clinical responses observed in earlier studies. To date, 225Ac-lintuzumab has only been studied in patients with overt leukemia. The aim of this phase 1 study is to identify the maximum tolerated dose (MTD) of 225Ac-lintuzumab that can be given safely to AML patients in the postremission setting in order to eliminate detectable MRD and ultimately prolong PFS and OS.

Actinium-225-Lintuzumab in Patients With Acute Myeloid Leukemia

Postremission Therapy With Actinium-225 (225Ac)-Lintuzumab (Actimab-A®) in Patients With Acute Myeloid Leukemia

The 3+3 dose-escalation is designed to establish the MTD of postremission therapy with 225Ac-lintuzumab in patients with AML in first, second, or third CR/CRp who have detectable minimal residual disease (MRD) and have completed all planned therapy.

The length of time during and after the treatment of AML that a subject lives with the disease but it does not get worse. It will be calculated from the time of study entry to relapse, death or last follow-up. That includes subjects with at least one cycle of therapy.

The Length of time in days during and after the treatment of AML that a subject lives. It will be calculated from the time of entry onto study to death or last follow-up. That includes all subjects who receive at least one cycle of therapy.

Joseph Jurcic

Assistant Professor of Medicine at the Columbia University Medic, Dept of Med Hematology & Onc

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Entinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Eligible patients will be enrolled according to Simon's two-stage design. The dose of Entinostat is 5 mg (one tablet) orally, once every week in a 28 day cycle.

Dose is 5 mg orally every week (days 1, 8, 15, and 22) of a 28 day treatment cycle. Study drug should be taken in the morning and on an empty stomach, at least 2 hours after a meal and at least 1 hour before the next meal. Tablets should be taken whole and not crushed.

Antonio Fojo, MD, PhD

This is an open-label, single arm, multi-center Phase II trial of entinostat given as a 5 mg oral dose every week (days 1, 8, 15, and 22 of a 4-week cycle) in patients with relapsed or refractory abdominal neuroendocrine (NE) tumors. Patients will continue on treatment until disease progression or intolerable toxicity occurs.

Neuroendocrine tumors (NETs) are derived from NE cells that reside widely in the endocrine system and other organs and comprise a heterogeneous group of neoplasms. Because NETs can arise in a broad spectrum of locations they are associated with a broad range of symptoms that may be caused by mass effects and/or by the production of hormones or biogenic amines.

Most recently, entinostat has been shown to down-regulate the number and function of two key immunosuppressive cells, myeloid derived suppressor cells (MDSCs) and regulatory T-cells (Tregs), in the tumor microenvironment thereby enhancing the activity of immune checkpoint inhibition. To date, entinostat has been investigated alone or in combination in \>900 patients with cancer in clinical studies, including \>600 patients with solid tumors. Entinostat as a single agent has been studied in metastatic melanoma and in combination has been studied in metastatic non-small cell lung cancer (NSCLC), breast cancer, renal cell cancer, and colon cancer.

Entinostat Neuroendocrine (NE) Tumor

A Phase 2 Single-Arm Multicenter Study of Entinostat in Patients With Relapsed or Refractory Abdominal Neuroendocrine (NE) Tumors

Percentage of patients who experience a tumor size reduction from the time of initial response to tumor progression.

Time from study enrollment until disease progression or death.

The length of time from either the date of diagnosis or start of treatment that years patients diagnosed with the disease are still alive.

Time from documentation of tumor response to disease progression.

Antonio Fojo

Professor of Medicine

Digestive System Diseases

Skin and Connective Tissue Diseases

Gastrointestinal Stromal Tumors

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pembrolizumab

Antibodies

Immunoglobulins

Imatinib Mesylate

Subjects will receive epacadostat and pembrolizumab

Subjects will receive pembrolizumab 200 mg (flat dose) IV every 3 weeks on day 1 of a 21 day cycle.

Epacadostat will be dosed at 100 mg PO twice a day (BID) daily. Doses should be taken twice daily, in the morning and evening, approximately 12 hours apart, without regard to food.Doses will be self-administered, except on Cycle 2 Day 1, when the morning dose will be given at the study site clinic. Subjects will be required to keep a pill diary that will be provided to them.

Epacadostat

Richard D Carvajal, MD

Primary objective is to assess the efficacy of combined IDO and PD-1 inhibition in a single arm phase II trial of epacadostat and pembrolizumab in patients with advanced imatinib-refractory GIST, using a primary endpoint of overall response rate.

Secondary objectives are to evaluate the progression free survival (PFS), the overall survival (OS), the response rate and to evaluate the safety and tolerability of combined epacadostat and pembrolizumab treatment.

The investigator hypothesizes that treatment with epacadostat and pembrolizumab will increase the response rate compared to what has been historically achieved with salvage tyrosine kinase inhibitors.

While targeted therapy with imatinib has significantly improved survival for patients with inoperable and metastatic gastrointestinal stromal tumors (GIST), the majority will eventually progress after a median of 20-26 months. Standard second-line treatment with sunitinib has a response rate of 7%, and third-line treatment with regorafenib has a response rate of only 5%. More effective treatments for imatinib-refractory GIST are needed.

This study aims to assess the efficacy of combined IDO and PD-1 inhibition with epacadostat (IDO inhibitor) and pembrolizumab (anti-PD-1 antibody) in patients with imatinib-refractory GIST.

Epacadostat and Pembrolizumab in Patients With GIST

A Phase II Study of Epacadostat and Pembrolizumab in Patients With Imatinib Refractory Advanced Gastrointestinal Stromal Tumors

The primary endpoint is the overall response rate as defined as the best response using RECIST v1.1 criteria. A standard way to measure how well a cancer patient responds to treatment. It is based on whether tumors shrink, stay the same, or get bigger. To use RECIST, there must be at least one tumor that can be measured on x-rays, CT scans, or MRI scans. The types of response a patient can have are a complete response (CR), a partial response (PR), progressive disease (PD), and stable disease (SD). Also called Response Evaluation Criteria In Solid Tumors.

The length of time from the start of treatment that patients diagnosed with the disease are still alive.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Evaluating NEOadjuvant Immunotherapy in Resectable PANCreatic Ductal Adenocarcinoma	NCT03979066	Pancreatic Duct...	Atezolizumab PEGPH20	18 Years - 99 Years	Columbia University
Actinium-225-Lintuzumab in Patients With Acute Myeloid Leukemia	NCT03705858	Acute Myeloid L...	Ac-Lintuzumab	18 Years - 99 Years	Columbia University
Entinostat Neuroendocrine (NE) Tumor	NCT03211988	Neuroendocrine ...	Entinostat	18 Years - 99 Years	Columbia University
Epacadostat and Pembrolizumab in Patients With GIST	NCT03291054	Gastrointestina...	Pembrolizumab Epacadostat	18 Years -	Columbia University

Spots Global Cancer Trial Database for columbia

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

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