GSK-3β is a potentially important therapeutic target in human malignancies. The Actuate 1801 Phase 1/2 study is designed to evaluate the safety and efficacy of 9-ING-41, a potent GSK-3β inhibitor, as a single agent and in combination with cytotoxic agents, in patients with refractory cancers.

9-ING-41 is a first-in-class, intravenously administered, maleimide-based small molecule potent selective GSK-3β inhibitor with significant pre-clinical antitumor activity. GSK-3 is a serine/threonine kinase initially described as a key regulator of metabolism and has a role in diverse disease processes including cancer, immune disorders, pathologic fibrosis, metabolic disorders, and neurological disorders. GSK-3 has two ubiquitously expressed and highly conserved isoforms, GSK-3α and GSK-3β, with both shared and distinct substrates and functional effects. GSK-3β is particularly important in tumor progression and modulation of oncogenes (including beta-catenin, cyclin D1 and c-Myc), cell cycle regulators (e.g. p27Kip1) and mediators of epithelial-mesenchymal transition (e.g. zinc finger protein SNAI1, Snail). Aberrant overexpression of GSK-3β has been shown to promote tumor growth and chemotherapy resistance in various solid tumors including colon, ovarian, and pancreatic cancers and glioblastoma through differential effects on the pro-survival nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Myc pathways as well on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and p53-mediated apoptotic mechanisms. GSK-3β helps maintain malignant cell survival and proliferation, particularly in terms of mediating resistance to standard anti-cancer therapies, through the NF-κB pathway. GSK-3β has been established as a potential anticancer target in human bladder, breast, colorectal, glioblastoma, lung, neuroblastoma, ovarian, pancreatic, prostate, renal and thyroid cancers as well as chronic lymphocytic leukemia and lymphomas.

9-ING-41 is a small molecule potent selective GSK-3β inhibitor with broad spectrum pre-clinical antitumor activity. It's modes of action include downregulation of NF-κB and decreasing the expression NF-κB target genes including cyclin D1, Bcl-2, anti-apoptotic protein (XIAP) and B-cell lymphoma-extra large (Bcl-XL) leading to inhibition of tumor growth in multiple solid tumor cell and lymphoma lines and patient derived xenograft (PDX) models. NF-κB is constitutively active in cancer cells and promotes anti-apoptotic molecule expression. NF-κB activation is particularly important in cancer cells that have become chemo- and/or radio-resistant. 9-ING-41 also has significant activity in pre-clinical models of pathological pleural and pulmonary fibrosis. 9-ING-41 has significant in vitro and in vivo activity as a single agent and/or in combination with standard cytotoxic chemotherapies in a spectrum of solid tumors and hematological malignancies including bladder, breast, glioblastoma, neuroblastoma, pancreatic, sarcomas, and renal cancers as well as lymphomas.

The 1801 had three parts:

* Completed: Part 1 (9-ING-41 as monotherapy): The standard 3+3 dose escalation design will be applied to all dose cohorts until the Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) is identified.
* Completed: 9-ING-41 combined with standard anticancer agents: The 3+3 dose escalation study design will be used for 8 chemotherapy combination regimens (9-ING-41 plus gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, nab-paclitaxel plus gemcitabine, paclitaxel plus carboplatin, pemetrexed plus carboplatin) to identify the MTD/RP2D of each regimen.
* Part 3: A randomized Phase 2 study of 9-ING-41 either once or twice weekly with gemcitabine and nab-paclitaxel (GA) versus GA alone for patients with previously untreated metastatic or locally advanced pancreatic cancer is now open.

Rhode Island Hospital

Mayo Clinic

Arizona Oncology Associates

The University of Arizona Cancer Center

University of California Irvine Health

UCSF Helen Diller Family Comprehensive Cancer Center

Christiana Care Health Services

Sibley Memorial Hospital

Florida Cancer Specialists - South

Miami Cancer Institute

Florida Cancer Specialists - North

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Des Moines Oncology Research Association

Kansas University Cancer Center

Ochsner Clinic Foundation

University of Michigan

MetroMetro-Minnesota Community Oncology Research Consortium (MMCORC)

Comprehensive Cancer Centers of Nevada

Morristown Medical Center

Capital Health Medical Center/ Hopewell

MD Anderson Cancer Center at Cooper

Columbia University- Irving Medical Center

Stony Brook University Hospital

Duke University Medical Center

Oregon Health and Science University

St. Luke's University Health Network

Allegheny Health Network

Prisma Health Cancer Institute

Sanford Research

West Cancer Center

Baptist Clinical Research Institute

Sarah Cannon Research Institute- Tennessee Oncology-Nashville

Vanderbilt-Ingram Cancer Center

Texas Oncology- Charles A. Sammons Cancer Center

UT Southwestern Medical Center

Utah Cancer Specialists

Fred Hutchinson Cancer Research Center

West Virginia University

UW Carbone Cancer Center

UZA- Antwerpen

Imelda VZW

UZ Gent

UZ Leuven Gasthuisberg

Cross Cancer Institute

QE II Health Sciences Centre

Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre

Jewish General Hospital

McGill University Health Centre

Centre Hospitalier Universitaire de Sherbrooke

Center Hospitalier Regional Universitaire de Besancon - Site Jean Minjoz

CHRU Brest Hopital Morvan

Hopital Claude Huriez

Institute de Cancerologie de Lorraine

Institut Bergonie

Insitut de Cancerologie de l'Ouest

Hopital de la Timone

Netherlands Cancer Institute

Fundacao Champalimaud

Hospital Da Luz

Centro Hospitalar Universitario Sao Joao

Vall d'Hebron Institute of Oncology

Institut Catala d'Oncologia

Hospital Clinico U San Carlos (HSC)

START Madrid-HM CIOCC Hospital Universitario

INCLIVA University of Valencia

9-ING-41 in Patients with Advanced Cancers

This phase IIa trial studies the side effects of abemaciclib monotherapy in treating patients age 70 years and older with hormone receptor positive, HER2 negative breast cancer that has spread to other places in the body.

Joanne Mortimer, MD

PRIMARY OBJECTIVE:

I. To estimate the incidence of grade 3 or higher toxicities attributed to abemaciclib monotherapy in adults aged 70 or older with hormone receptor positive metastatic breast cancer.

SECONDARY OBJECTIVES:

I. To describe the full toxicity profile including all grade 2 and higher adverse events, and patient-reported adverse events (AEs) using Patients Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) measures.

II. To describe rates of dose reductions, dose holds, treatment discontinuations due to factors other than progression, and hospitalizations.

III. To estimate median (and 95% confidence interval \[CI\]) failure-free survival, progression-free survival and overall survival.

IV. To describe the results of Was It Worth It (WIWI) and Overall Treatment Utility (OTU) questionnaires.

V. To describe the rate of adherence to abemaciclib. VI. To determine average plasma steady-state abemaciclib Ctrough concentrations.

VII. To evaluate the association of adherence rate with abemaciclib plasma t-rough concentrations.

VIII. To describe associations between cancer-specific, comprehensive Geriatric Assessment (cGA) scores and the incidence of toxicities and their grade.

EXPLORATORY OBJECTIVE:

I. To determine the association between biomarkers of aging and grades 3 or higher toxicity.

OUTLINE:

Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 6 months for 2 years.

Dana Farber Cancer Institute

Mina Sedrak

City of Hope Medical Center

Rachel Freedman, MD

Ellis Levine, MD

Roswell Park Comprehensive Cancer Center

Abemaciclib and Endocrine Therapy in Older Patients with Breast Cancer.

This research study is studying a drug called Abemaciclib as a possible treatment for have metastatic triple-negative type of breast cancer.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved abemaciclib as a treatment for any disease.

Some triple-negative breast cancers show expression of the Rb protein and are referred to as "Rb-positive." The Rb protein is important because it controls the way that cancer cells divide and grow. Drugs like abemaciclib work by changing the way that Rb functions. This can potentially stop cancer cells from dividing, and can also potentially lead to cancer cell death.

In this research study, the investigators are are looking to see how safe abemaciclib is and how well it will work to help people with triple-negative breast cancer that is Rb-positive.

EPSG:4326

Dana-Farber Cancer Institute

Abemaciclib for Patients With Retinoblastoma-Positive, Triple Negative Metastatic Breast Cancer

This study will evaluate the effect of adding abemaciclib to fulvestrant for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer that progressed or recurred after previous treatment with a type of drug known as a CDK4/6 inhibitor and endocrine therapy. Participation could last up to 5 years, depending on how you and your tumor respond.

Massachusetts General Hospital

Mass General Cancer Center

Vernon Cancer Center Pharmacy, Massachusetts General Cancer Center at Newton-Wellesley

MGH Northshore Cancer Center

Dana-Farber Cancer Institute - Foxborough

Dana Farber Cancer Center Merrimack Valley

Dana Farber Cancer Center Institute - Milford

Reliant Medical Group

Lifespan Cancer Institute

Dana Farber Cancer Center Londonderry

Southcoast Centers for Cancer Care

New England Cancer Specialists

St. Joseph's Hospital and Medical Center

Highlands Oncology Group

Providence Medical Foundation

Cancer and Blood Specialty Clinic

TRIO-US (Translational Research in Oncology-US)

Keck School of Medicine of USC

UCLA Hematology/Oncology - Parkside

Olive View-UCLA Medical Center

Torrance Memorial Physician Network / Cancer Care

PIH Health Hematology Medical Oncology

Rocky Mountain Cancer Center - Hale Parkway

Florida Cancer Specialists SOUTH/Sarah Cannon Research Institute/SCRI

Millennium Oncology Research Clinic

University of Miami Hospital and Clinics, Sylvester Cancer Center

Woodlands Medical Specialists, PA

Florida Cancer Specialists EAST/Sarah Cannon Research Institute/SCRI

Winship Cancer Institute, Emory University

Northeast Georgia Medical Center

Central Georgia Cancer Care

Kapiolani Medical Center for Women and Children

Ingalls Memorial Hospital

Hematology Oncology Clinic- Baton Rouge/Sarah Cannon Research Institute/SCRI

Clinical Trials of SWLA

Central Maine Medical Center

Mfsmc-Hjwci

Maryland Oncology Hematology, P.A. - Clinton

St. Vincent Frontier Cancer Center

University of New Mexico Comprehensive Cancer Center

Tennessee Oncology-Chattanooga /Sarah Cannon Research Institute/SCRI

Sarah Cannon Research Institute/SCRI

Tennessee Oncology-Nashville/Sarah Cannon Research Institute/SCRI

Texas Oncology - Bedford

Texas Oncology - Denton

Texas Oncology, P.A.

University of Texas MD Anderson Cancer Center

Texas Oncology - McKinney

Texas Oncology - Plano East

Texas Oncology-Plano West

Mays Cancer Center

US Oncology

Texas Oncology - Tyler Cancer Center

Intermountain Medical Center

Intermountain Healthcare - St. George

The University of Vermont Medical Center Inc.

Shenandoah Oncology, P.C.

Fundación Respirar

Centro de Investigaciones Metabólicas (CINME)

Fundación Cenit Para La Investigación En Neurociencias

Instituto Médico Río Cuarto

Centro Medico San Roque

CER San Juan

Algemeen Ziekenhuis klina

Jessa Ziekenhuis

CHU UCL Namur/Site Sainte Elisabeth

Multiscan

Fakultni nemocnice Hradec Kralove

Herlev and Gentofte Hospital

Regionshospitalet Gødstrup

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

CHRU de Brest

Hôpital privé du Confluent SAS

CHD Vendee

University Hospital of Patras

Alexandra Hospital

University General Hospital of Heraklion

Euromedica General Clinic of Thessaloniki

Bacs-Kiskun Megyei Korhaz

Petz Aladar Egyetemi Oktato Korhaz

Magyar Honvedseg Egeszsegugyi Kozpont

Országos Onkológiai Intézet

Soroka Medical Center

Meir Medical Center

Rabin Medical Center

Sheba Medical Center

Sourasky Medical Center

Hadassah Medical Center

Humanitas Istituto Clinico Catanese

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"

P.O. "S. Maria della Misericordia" Azienda Sanitaria Universitaria Friuli Centrale

Instituto Tumori Giovanni Paolo II

Ospedale Misericordia di Grosseto

Ospedale San Raffaele

ASL Viterbo Ospedale Belcolle

Seoul National University Bundang Hospital

Korea University Anam Hospital

Abemaciclib (LY2835219) Plus Fulvestrant Compared to Placebo Plus Fulvestrant in Previously Treated Breast Cancer

The purpose of this research study is to evaluate a decision aid to help women aged 70 and older decide on treatment for their breast cancer.

The investigators aim to use this information to further refine and evaluate a decision aid to help newly-diagnosed women aged 70 and older with breast cancer understand the risks and benefits of different types of breast cancer treatment. The Decision Aid (DA) was created for women 70 years or older diagnosed with ER+, HER2-, clinically LN-, 3cm or less breast cancers deciding on breast cancer treatment. The DA was designed considering the health literary, cognitive abilities, treatment outcomes, and competing health issues of older women.

Phase I :

- The investigators will obtain and incorporate additional feedback on the DA from women 70 years or older who were diagnosed with breast cancer > 6 months ago, their family members, and clinicians, so that the DA can be refined and evaluated by women who were recently treated for breast cancer but not newly diagnosed with breast cancer.

Phase II

- The investigators plan to test the efficacy of the revised DA in a randomized control trial (RCT) of 230 diverse women 70 years or older newly diagnosed with ER+, LN-, HER2-, 3 cm or less breast cancer.

Beth Israel Deaconess Medical Center

A Breast Cancer Treatment Decision Aid for Women Aged 70 and Older

The main purpose of this study is to learn if adding bevacizumab to standard treatment with chemotherapy (docetaxel, doxorubicin, and cyclophosphamide) for early stage HER2-negative breast cancer will prevent breast cancer from returning. A second purpose of this study is to learn if adding bevacizumab to treatment with chemotherapy will help women with HER2-negative breast cancer live longer. The researchers also want to learn about the side effects of the combination of drugs used in this study.

The B-46-I/07132 study, a multicenter, open-label, randomized Phase III, adjuvant therapy trial, will compare the value of adding bevacizumab to a non-anthracycline-based chemotherapy regimen relative to the same chemotherapy without bevacizumab and relative to an anthracycline-based chemotherapy regimen in women with resected node-positive or high-risk node-negative, HER2-negative breast cancer. This trial will determine whether the addition of bevacizumab to a regimen of docetaxel and cyclophosphamide (TCB) improves invasive disease-free survival relative to docetaxel and cyclophosphamide alone (TC). A secondary aim will be to determine whether the addition of bevacizumab to TC improves invasive disease-free survival compared to a regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC). Other secondary aims include whether TCB improves disease-free survival, overall survival, and recurrence-free interval relative to TC alone and to TAC. The toxicities of the three regimens will also be compared.

Patients in the B-46-I/07132 study will be randomized to one of three treatment regimens: Group 1 patients will receive 6 cycles of TAC administered every 21 days (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2); Group 2 patients will receive 6 cycles of TC administered every 21 days (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2); and Group 3 patients will receive 6 cycles of TCB every 21 days with bevacizumab therapy continuing every 21 days after completion of chemotherapy until 1 year following the first dose (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2, and bevacizumab 15 mg/kg). Primary prophylaxis with pegfilgrastim or filgrastim is required for Group 1 patients (optional for patients in Groups 2 and 3). Patients will also receive adjuvant radiation therapy as clinically indicated and endocrine therapy for hormone receptor-positive tumors.

Tumor samples will be submitted for correlative science studies to evaluate predictors of study therapy benefit. Submission of a tumor sample is a study requirement for all patients.

Saint Anne's Hospital

Hartford Hospital

University of Connecticut

Birmingham Hematology and Oncology

Birmingham Hematology and Oncology - Brookwood

Birmingham Hematology and Oncology - Princeton

Birmingham Hematology and Oncology - Montclair

Birmingham Hematology and Oncology - Pilot

Clearview Cancer Institute- Huntsville

Northern Arizona Hematology & Onclogy Associates

Arizona Oncolocy (CASA-Green Valley)

Arizona Oncology (CASA- Oro Valley)

Hematology Oncology Associates

A Clinical Trial Comparing the Combination of TC Plus Bevacizumab to TC Alone and to TAC for Women With Node-Positive or High-Risk Node-Negative, HER2-Negative Breast Cancer

Breast Cancer > Boston, MA, USA

Sort: