Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Tissue Adhesions

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Administered orally BID in a 21 day cycle

defactinib (VS-6063)

David E Gerber, M.D.

This is a Phase II, open-label, multicenter, multi cohort, study of VS-6063 (defactinib), a focal adhesion kinase inhibitor, in patients with KRAS mutant non-small cell lung cancer (NSCLC). NSCLC with a KRAS mutation is required for study entry and subjects will be enrolled into 1 of 4 cohorts based on the status of their INK4a/Arf and p53 mutations. The purpose of this study is to demonstrate if VS-6063 (defactinib) improves PFS within each cohort. The safety and tolerability of VS-6063, tumor response rate, progression free survival and overall survival will also be assessed. The pharmacodynamic effects of VS-6063 (defactinib) will be examined in a tumor biopsy and a blood sample.

Eleven subjects will be enrolled into one of four cohorts: Cohort A (KRAS mutation, wild type INK4a/ARF and wildtype p53), Cohort B (KRAS mutation, INK4s/ARF mutation and wild type p53), Cohort C (KRAS mutation, wild type INK4a/ARF and p53 mutation), and Cohort D (KRAS mutation, INK4a/ARF mutation and p53 mutation). If \>/= 4 patients demonstrate PFS at 12 weeks in each cohort, an additional 23 subjects will be enrolled.

Phase II Study of VS-6063 in Patients With KRAS Mutant Non-Small Cell Lung Cancer

Phase II Study of VS-6063, A Focal Adhesion Kinase (FAK) Inhibitor, in Patients With KRAS Mutant Non-Small Cell Lung Cancer

Adverse events (AEs) include the incidences of all treatment-emergent AEs (TEAEs) and all Serious Adverse Events (SAEs); by severity, relationship to study drug, and discontinuation of patients from study therapy due to AEs and due to deaths. Safety endpoints for AEs, clinical laboratory tests, vital signs, ECGs and physical examinations will be summarized using descriptive statistics as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03

RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.

PFS will be estimated in each cohort using Kaplan-Meier product limit estimates.

OS in each cohort will be estimated using Kaplan-Meier product limit estimates.

Verastem, Inc.

Neoplasm Metastasis

Neoplastic Processes

Oral VS-4718 administered BID (QD during first cohort) during a 28 day cycle.

VS-4718

Hagop Youssoufian, MD

This is a Phase I, open-label, multicenter, dose-escalation trial of VS-4718, a focal adhesion kinase inhibitor, in subjects with metastatic non-hematologic malignancies. This clinical study is comprised of 2 parts: Part 1 (Dose Escalation) and Part 2 (Expansion). The purpose of this study is to evaluate the safety (including the recommended Phase II dose), pharmacokinetics (the amount of VS-4718 in your blood) and the anti-cancer activity of VS-4718. The pharmacodynamic effects (genes or proteins that may predict or show how your body may respond to VS-4718) will also be examined in tumor biopsies and blood samples.

Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies

A Phase I Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Subjects With Metastatic Non-Hematologic Malignancies

Serious Adverse events, Adverse events and their frequency, duration and severity, physical examination, laboratory parameters, vital signs and ECGs as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) V4.03. A Safety monitoring committee will review safety information.

The RP2D will be determined based on the maximum tolerated dose (MTD) of VS-4718 as determined by number of participants with dose limiting toxicities related to VS-4718. Observations related to pharmacokinetics, pharmacodynamics, and any VS-4718 related toxicities may be included in the rationale supporting the RP2D and will not exceed the MTD.

Response rate and progression-free survival as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1

PK (pharmacokinetics) parameters, including but not limited to clearance, plasma concentration, AUC (Area Under Curve, 0-24 and 0-t), Cmax, Tmax, and T1/2

Pre and post dose biomarker analysis in serum and tumor samples to identify possible prognostic factors to VS-4718 response

Tumor expression status (pFAK, cancer stem cells, CSC, and other biomarkers) compared with response to VS-4718, as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1

Oral defactinib (VS-6063) administered twice a day (BID) during a 21 day cycle.

Defactinib

Hagop Youssoufian, m

This is a phase I, open-label, dose-escalation trial of defactinib (VS-6063), a focal adhesion kinase inhibitor, in Japanese patients with non-hematologic malignancies. The purpose of this study is to assess the safety (including the recommended phase 2 dose), the pharmacokinetics, and the anti-cancer activity of defactinib (VS-6063).

Phase I Dose Escalation Study of VS-6063 in Japanese Subjects With Non-Hematologic Malignancies

A Phase I Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of VS-6063, a Focal Adhesion Kinase Inhibitor, in Japanese Subjects With Non-Hematologic Malignancies

A composite by dose level to include incidence of AEs, SAEs, dose interruptions and dose reductions as a measure of safety and tolerability. Abnormal Clinical significant laboratory results, ECG measurements, vital signs measurement, physical examination findings, and ECOG performance status were captured as adverse events.

The severity of AEs were evaluated according to CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03

The RP2D will be determined based on the MTD of defactinib (VS-6063) as determined by number of participants with dose limiting toxicities (DLTs) related to defactinib.

PK parameters, including but not limited to plasma concentration, AUC (Area Under Curve) 0-t, Cmax, Tmax, and T1/2. Total 24-hour urine output will be collected in conjunction with PK sampling to assess the elimination of defactinib (VS-6063) and its potential metabolites.

Response rate and progression-free survival, as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1

The systematic method was through regular investigator assessment and regular laboratory testing.

Defactinib 200 mg Bid

Defactinib 400 mg Bid

Defactinib 600 mg Bid

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Lou Vaickus, MD, FACP/Chief Medical Officer

At least 1 TEAE (treatment emergent AE)

At least 1 TEAE related to study drug

Non-Lab TEAE with Severity ≥ Grade 3

Lab TEAE with Severity ≥ Grade 3

At least 1 Serious TEAE

Dose Interruptions

Dose Reductions

Assess the Safety and Tolerability of Defactinib (VS-6063) in Japanese Subjects With Non-hematologic Malignancies

Define the Maximum Tolerated Dose (MTD), if Achieved, and Establish the Recommended Phase 2 Dose (RP2D) of Defactinib (VS-6063) in Japanese Subjects.

Assess the Pharmacokinetics, Metabolism and Elimination of Defactinib (VS-6063) in Plasma and Urine.

Evaluate the Efficacy (Response Rate and Progression-free Survival) of Subjects Treated With Defactinib (VS-6063).

200 mg bid (twice a day) po (by mouth) defactinib

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Uterine Cervical Neoplasms

Breast Neoplasms

Colorectal Neoplasms

Breast Diseases

Skin Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

The usual care group received usual care that varies dependent upon the practice setting.

TIWeb (Tailored Web Intervention) program is interactive and tailored to the participant's individual beliefs and demographics. Individuals receiving the TIWeb will be given information that allows them to call and receive an FOBT kit in the mail or schedule an appropriate CRC test and/or mammogram.

CSC - a telephone counseling call during which the participant is given the opportunity to complete CRC screening (FOBT or a colonoscopy) and/or mammography screening.The CSC included tailored counseling as well as the ability to schedule BC and CRC screening tests.

TIWeb + CSC ((Tailored web intervetion+Cancer screening) group receive a mailed TIWeb, which is followed in four weeks by a CSC with the same opportunity to receive FOBT kits or schedule a colonoscopy and/or mammogram. The nurse counselor, knowing the participant is a good candidate for screening tests, will be trained to schedule CRC or BC screening appointments or to mail FOBT kits to individuals in the intervention groups even if they have not had a recent clinic visit.

Intervention: TIWeb program is interactive and tailored to the participant's individual beliefs and demographics. Individuals receiving the TIWeb will be given information that allows them to call and receive an FOBT kit in the mail or schedule an appropriate CRC test and/or mammogram.

TIWeb

Intervention: CSC - a telephone counseling call during which the participant is given the opportunity to complete CRC screening (FOBT or a colonoscopy) and/or mammography screening.The CSC included tailored counseling as well as the ability to schedule BC and CRC screening tests.

Intervention: The usual care group received usual care that varies dependent upon the practice setting.

Intervention: TIWeb + CSC ((Tailored web intervetion+Cancer screening) group receive a mailed TIWeb, which is followed in four weeks by a CSC with the same opportunity to receive FOBT kits or schedule a colonoscopy and/or mammogram. The nurse counselor, knowing the participant is a good candidate for screening tests, will be trained to schedule CRC or BC screening appointments or to mail FOBT kits to individuals in the intervention groups even if they have not had a recent clinic visit.

TIWeb+CSC

Victoria Champion, PhD

This study compares the efficacy (adherence and stage) of four interventions to promote colorectal (CRC) and breast cancer (BC) screenings among women ages 50 to 75. They are:

1. usual care;
2. a TIWeb (tailored intervention Website)
3. a CSC (cancer screening call) and
4. TIWeb + a CSC. This study also compares the cost-effectiveness of the 4 interventions to promote CRC and BC screening among women ages 50 to 75.

This study addresses innovative approaches to increase adherence to screening tests for colorectal and breast cancer - two cancers that have the greatest impact on female cancer mortality in the United States.The cancer burden in women could be significantly reduced by increasing participation in recommended screening for colorectal cancer (CRC) and breast cancer (BC) in all eligible women. This research tests intervention to simultaneously increase both CRC and BC screening using behavior change strategies, and also estimates the efficacy and cost-effectiveness of the interventions. Two groups of women, Group A (adherent to BC screening guidelines, but NOT to CRC screening guidelines) and Group B (non-adherent to BC \& CRC guidelines) are randomized to 1. Usual Care, 2. TIWeb, 3. CSC and 4. TIWeb +CSC.

We propose a prospective randomized 2x2 factorial design: 1)usual care; 2) a TIWeb; 3) a Cancer Screening Call (CSC), and 4 a TIWEB+ a Cancer Screening Call (CSC). The intervention will be tested in 2 groups of women. Group A will include women who are nonadherent to CRC but adherent to BC screening guidelines. Group B will include women who are nonadherent to both CRC and BC screening guidelines.

Increasing Colorectal and Breast Cancer Screening in Women

De-identified IPD will be made available to other researchers through a HIPAA compliant data storage system (Box Health) that is password protected.

any CRC test (either a stool test or colonoscopy) receipt of a stool test or a colonoscopy

Forward stage movement is the desired outcome -determining any forward stage movement in considering CRC screening either from Precontemplation to contemplation or from precontemplation to action

Comparing the cost-effectiveness of four conditions to promote CRC and BC screening , there will be differences in adherence to both CRC and BC screening and stage of adoption, among women who are randomized to 1) usual care; 2) a TIWeb; 3) a CSC, and 4) a TIWeb plus a CSC.

National Cancer Institute (NCI)

Indiana University

Distinguished Professor Edward and Sara Stam Culliper named Professor Associate Director Cancer Prevention and Control

Rare Diseases

Esophageal Neoplasms

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

The staging ultrasound endoscopy is performed on patients previously diagnosed with esophageal cancer via diagnostic biopsy. The staging ultrasound identifies affected lymph nodes and depth of tumor to the esophageal wall. The tumor sampling is via a biopsy forcep (one pass to obtain 100 cells).

Tumor Biopsy via Ultrasound Endoscopy

Anthony Capobianco, MD

Cancer results when undifferentiated cells grow in an uncontrolled manner, crowding out normal cells, causing morbidity and ultimately mortality. the cancer stem cell theory suggests that most tumors undergo a process of differentiation through which a relatively rare cancer stem or progenitor cell (CSC) gives rise to more differentiated populations of cells (including transiently amplifying cells) comprising the bulk of the tumor. As a result of this cellular diversity, one or more cells within the tumor are likely to be resistant to therapy. Among cells resistant to a given therapy, only CSCs can repopulate the tumor. A key feature of this resistant subset of CSCs is that they repopulate a tumor resistant to the original intervention. The cellular programs driving the uncontrolled proliferation of many solid tumors result from aberrant activity of Wnt, Shh, and/or Notch signaling pathways in esc. Thus, therapies that down-regulate the activity of these fundamental pathways in CSCs will be effective in the treatment of cancer. The investigator's research program focuses on the elucidation of signaling mechanisms, control of cellular processes and discovery of small molecules that selectively target Wnt, Shh, and Notch signaling pathways that are fundamental to CSCs. Our preliminary results identified a novel Notch associated protein NACK that functions as a transcriptional co-activator of Notch. Moreover, Nack is expressed in human solid tumors and is required for cell survival and tumor growth in notch -dependent tumor cells.

The investigator's aim is to further interrogate the link between Notch and Nack.

Specific Aims:

* Identify and isolate the cancer stem cell populations from primary chemo naive esophageal tumor samples.
* Interrogate the status of the Notch,( the link between Notch and Nack), Wnt and Hedghog pathways in the chemo naive esophageal tumor as well as in specific cell populations, such as the CSC.
* Determine the degree of cross-talk between these pathways and which of these pathways is essential for the self renewal properties and tumorigenic properties of the esc population.
* Identify critical targets for therapeutic intervention in CSC populations.

Wnt, Notch and Hedgehog Activity in Chemo-Naive Tumors Collected During Staging of Esophageal Cancer Patients

Interrogation of Wnt, Notch, and Hedgehog Activity in Chemonaive Tumors Collected During the Staging Ultrasound Endoscopies of Patients Diagnosed With Esophageal Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase II Study of VS-6063 in Patients With KRAS Mutant Non-Small Cell Lung Cancer	NCT01951690	Non Small Cell ... Lung Cancer	defactinib (VS-...	18 Years -	Verastem, Inc.
Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies	NCT01849744	Non Hematologic... Metastatic Canc...	VS-4718	18 Years -	Verastem, Inc.
Phase I Dose Escalation Study of VS-6063 in Japanese Subjects With Non-Hematologic Malignancies	NCT01943292	Non Hematologic...	Defactinib	20 Years -	Verastem, Inc.
Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies	NCT01849744	Non Hematologic... Metastatic Canc...	VS-4718	18 Years -	Verastem, Inc.
Increasing Colorectal and Breast Cancer Screening in Women	NCT03279198	Breast Cancer F... Colorectal Canc...	TIWeb CSC UC TIWeb+CSC	50 Years - 75 Years	Indiana University
Wnt, Notch and Hedgehog Activity in Chemo-Naive Tumors Collected During Staging of Esophageal Cancer Patients	NCT02221245	Esophageal Canc...	Tumor Biopsy vi...	18 Years -	University of Miami
Phase I Dose Escalation Study of VS-6063 in Japanese Subjects With Non-Hematologic Malignancies	NCT01943292	Non Hematologic...	Defactinib	20 Years -	Verastem, Inc.

Spots Global Cancer Trial Database for csc

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

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