Blood and Lymph Conditions

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

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Fanconi Anemia

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All Drugs and Chemicals

Prexasertib

Protein Kinase Inhibitors

Enzyme Inhibitors

Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Geoffrey Shapiro, MD, PhD

This research study is studying a checkpoint kinase 1 (CHK1) inhibitor as a possible treatment for advanced solid tumors that harbor genetic alterations in the homologous repair (HR) pathway, genetic alterations that indicate replication stress, or with CCNE1 amplification.

This is an open label, phase II, two-arm study exploring the anti-tumor activity of the CHK1 inhibitor prexasertib (LY2606368) in patients with advanced solid tumors exhibiting one of the following:

1. Replicative stress, including MYC amplification, CCNE1 amplification, Rb loss, or an FBXW7 mutation
2. An HR deficiency, including tumors with genomic or somatic mutations of BRCA1, BRCA2, PALB2, RAD51C, RAD51D, ATR, ATM, CHK2, or the Fanconi anemia pathway genes
3. A CCNE1 amplification

A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency

A Phase II Study of the CHK1 Inhibitor LY2606368 in Patients With Advanced Solid Tumors Exhibiting Replicative Stress or Homologous Recombination Repair Deficiency

Progression-Free Rate defines as the percentage of participants progression-free at 4 months in all arms, by RECIST 1.1 criteria. Progression-free rate will be estimated as binomial proportion and overall survival and progression-free survival estimates and curves will be generated using the Kaplan-Meier method.

All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEvE as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.

The objective response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Dana-Farber Cancer Institute

Geoffrey Shapiro M.D., PhD

Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.

Homologous Repair (HR) Deficiency Cohort

Replicative Stress Cohort

CCNE1 Amplification Cohort

Total

Age, Continuous

Sex: Female, Male

Non-Hispanic

Hispanic

Race/Ethnicity, Customized

United States

Region of Enrollment

Geoffrey Shapiro M.D., PhDDana-Farber Cancer Institute

>= 4 months

< 4 months

Progression-Free Rate at 4 Month

Incidence of Grade 4 Treatment-Related Toxicity

Objective Response Rate

Median Overall Survival (OS)

Prexasertib (LY2606368) will be administered as an IV infusion in patients with homologous repair (HR) deficiency on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Prexasertib (LY2606368) will be administered as an IV infusion in patients with advanced solid tumors exhibiting replicative stress on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Prexasertib (LY2606368) will be administered as an IV infusion in patients with CCNE1 amplification on day 1 and day 15 of every 28 day cycle. Prexasertib will be given at the recommended phase 2 dose of 105 mg/m2 administered over approximately 1 hour.

LY2606368

Overall Study

Neoplasms

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Prostatic Neoplasms

Breast Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

Talazoparib

Poly(ADP-ribose) Polymerase Inhibitors

Participants receive Treatment B for 28 days, followed by Treatment A for 21 days, followed by Treatment C for 21 days.

Participants receive Treatment A for 28 days, followed by Treatment B for 21 days, followed by Treatment C for 21 days.

Current commercial talazoparib formulation 1 mg once daily given under fasting condition

TALZENNA capsule

Proposed talazoparib soft gel capsule formulation 1 mg once daily under fasting condition

Talazoparib soft gel capsule

Proposed talazoparib soft gel capsule formulation 1 mg once daily under fed condition

Pfizer CT.gov Call Center

This will be a Phase 1, open label, 2-sequence, crossover study to establish the BE of the current commercial formulation (Generation 3.1 talazoparib capsules) to the proposed talazoparib liquid-filled soft gelatin capsule (soft gel capsule) formulation after multiple dosing under fasting conditions in participants with advanced solid tumors. In addition, the effect of food on the PK of the proposed talazoparib soft gel capsule formulation will be evaluated in fixed sequence after the 2 BE assessment periods.

Participants will be randomly assigned to 1 of 2 sequences to receive Treatment A, B and C in different order as shown below. The first 2 periods will be for BE assessment, with the first period being 28 days and the following periods being 21 days. Period 3 will be a 21 day period to evaluate the food effect on the PK of the proposed talazoparib soft gel capsule formulation that will be included in the fixed sequence after the 2 BE assessment periods (for participants who can tolerate one high-fat/high-calorie meal). Participants must have received 21 consecutive days of continuous 1mg QD drug administration to be considered as completers of a treatment period, before moving on to the next scheduled treatment.

A Bioequivalence Study Between the Proposed and Current Talazoparib Capsule Formulation and Food Effect Study for the Proposed Talazoparib Capsule Formulation in Participants With Advanced Solid Tumors

A PHASE 1, OPEN LABEL, CROSSOVER STUDY TO ESTABLISH BIOEQUIVALENCE BETWEEN THE PROPOSED SOFT GEL TALAZOPARIB CAPSULE FORMULATION AND THE CURRENT TALAZOPARIB COMMERCIAL FORMULATION AND TO ESTIMATE THE FOOD EFFECT ON PHARMACOKINETICS OF THE PROPOSED TALAZOPARIB SOFT GEL CAPSULE FORMULATION IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Area under the plasma concentration-time curve from time 0 to 24 hours

Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)

Incidence of AEs characterized by type, severity (graded by NCI CTCAE version 5.0), timing, seriousness and relationship to study treatment

Pfizer

Symptoms and General Pathology

Syndrome

Pancreatitis

Pancreatitis, Chronic

Cysts

Pancreatic Diseases

Pancreatic Cyst

Peutz-Jeghers Syndrome

Gastrointestinal Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Endocrine System Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Gastrointestinal Agents

Pancrelipase

Pancreatin

Patients that have a diagnosis or any family history of a hereditary pancreas cancer syndrome, such as, but not limited to, Familial Pancreatic Cancer, hereditary pancreatitis, FAMMM syndrome, FAP and its variants, HNPCC (Lynch syndrome), Peutz-Jeghers syndrome, or BRCA1 and/or BRCA2 germline mutations.

Patients that have personal or family history of pancreatic cancer or pancreatic cysts.

Patients that have a personal or family history of pancreatic dysplasia or inflammatory pancreatic diseases.

Arielle Labiner

Aimee Lucas, MD, MS

The purpose of this study is to establish a registry of patients with pancreatic diseases. Patients included in the registry may include those with: pancreatic cancer, precancerous lesions of the pancreas, inflammatory lesions of the pancreas, cystic lesions of the pancreas, and patients at high-risk of pancreatic cancer such as those with a family history of pancreatic cancer or with a family history of a syndrome known to be associated with pancreatic cancer. Pancreatic cancer is the fourth leading cause of death from cancer in the United States. However, little is known about the development of pancreatic cancer and pancreatic diseases in individuals with the above conditions. Knowledge of how family history, environmental exposures, and inflammatory lesion of the pancreas contribute to the development of pancreatic cancer and pancreatic diseases is essential.

You may qualify to take part in this research study because you have inflammation in the pancreas, a pancreatic cyst, pre-cancerous lesions of the pancreas, pancreatic cancer, a family history of pancreatic cancer, or a family history of a syndrome known to be associated with pancreatic cancer.

We will also be collecting a blood sample from all participants for DNA isolation. Sometimes we are born with genes or DNA that give us an increased or decreased chance of developing an illness later in life. Genetic material will be isolated from your blood for further study. You may also choose to provide additional blood samples for serum and plasma extraction. Serum and plasma are components of the blood which can be used to measure indicators of disease in the blood, called biomarkers,for pancreatic diseases. Clinical data and biological specimens contained in this study may be used for a wide variety of future related studies to the cause, diagnosis, outcome and treatment of pancreatic cancer.

Funds for conducting this research are provided by Mount Sinai.

The overall purpose of this research project is to establish a registry of patients with pancreatic diseases. Patients included in the registry may include those with: pancreatic cancer, precancerous lesions of the pancreas such as intraductal papillary mucinous neoplasms (IPMNs) and cystic lesions, inflammatory lesions and inflammation of the pancreas, and patients at high-risk of pancreatic cancer such as those with a family history of pancreatic cancer or with a family history of a syndrome known to be associated with pancreatic cancer. The data contained in this registry will be used to conduct research related to the risk of pancreatic cancer and pancreatic diseases. As this is a registry protocol, no specific hypotheses are to be tested.

Specific Aims:

1. Establish and maintain a registry of individuals and their family members who have pancreatic diseases and may be at increased risk of developing pancreatic cancer over normal population risk.
2. Collect data and review existing data on personal and family histories, demographics, risk factors, and health behaviors.
3. Use the data in the registry to conduct studies related to disease risk, prevention, and prognosis of pancreatic cancer and other pancreatic diseases.

Pancreatic cancer is the fourth leading cause of death from malignancy in the United States. With near equivalent incidence and mortality, cure can only be achieved with surgical resection of an early stage lesion. Premalignant disease stages, such as IPMN, may be detected with noninvasive and minimally invasive techniques, providing an opportunity for screening and surveillance of at-risk populations.

Knowledge of the etiology of pancreatic cancer is incomplete. Approximately 10% of pancreatic ductal adenocarcinoma (PDAC) has a hereditary component, and screening this population has the potential to have an impact on disease mortality. Certain patient populations, such as those with hereditary pancreatitis, Peutz-Jeghers syndrome, familial atypical multiple mole melanoma (FAMMM syndrome), Lynch syndrome, and the breast ovarian cancer syndrome (BRCA1 and BRCA2 mutations) are at the highest risk of PDAC. BRCA2 mutations are the most commonly identified germline mutations in families with PDAC. Even a family history of PDAC without the above described syndromes has been shown to increase risk, suggesting a unique familial pancreatic cancer syndrome which may be related to the partner and localizer of BRCA2 (PALB2) gene or other PDAC susceptibility genes. Environmental risk factors, such as cigarette smoking, diabetes, obesity and dietary risk factors have been implicated in the development of PDAC.

A sequential model of acquisition of somatic mutations via a Pancreatic Intraepithelial Neoplasia (PanIN) has been proposed for the development of PDAC and subsequent metastases. However, others have proposed that the metastatic process may be initiated earlier in the disease process during the pre-malignant cyst or PanIN phase. This may in part account for the fact that the overwhelming majority of patients diagnosed with PDAC are diagnosed when the lesion is already metastatic.

Several groups have instituted PDAC screening for individuals at high-risk of PDAC. These groups have demonstrated the feasibility of detection of PDAC and pre-malignant lesions in certain high-risk individuals. Given the large gaps in knowledge, recruitment of patients with preneoplastic pancreatic diseases to registries is essential in the development of effective PDAC screening and prevention programs.

As an increasing number of patients undergo cross-sectional imaging with the abdomen with cat scan (CT) and magnetic resonance imaging (MRI), an increasing number of patients are found to have pancreatic disease and pancreatic cysts. While there is an increased risk of pancreatic cancer with these lesions, the studies to date are small and retrospective.

Whole Blood samples for DNA, serum and plasma extraction.

Pancreas Registry and High Risk Registry

Pancreas Disease and High Risk Registry

Number of individuals and their family members who have pancreatic diseases and may be at increased risk of developing pancreatic cancer over normal population risk.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of LY2606368 (Prexasertib) in Patients With Solid Tumors With Replicative Stress or Homologous Repair Deficiency	NCT02873975	Advanced Cancer...	LY2606368	18 Years -	Dana-Farber Cancer Institute
A Bioequivalence Study Between the Proposed and Current Talazoparib Capsule Formulation and Food Effect Study for the Proposed Talazoparib Capsule Formulation in Participants With Advanced Solid Tumors	NCT04672460	Advanced Solid ... Solid Tumors Ovarian Cancer Breast Cancer Prostate Cancer NSCLC Pancreatic Canc... Colorectal Canc...	TALZENNA capsul... Talazoparib sof... Talazoparib sof...	18 Years - 70 Years	Pfizer
Pancreas Registry and High Risk Registry	NCT02775461	Pancreas Cancer Pancreatitis Chronic Pancrea... Pancreatic Cyst Family History ... Genetic Mutatio...		18 Years -	Icahn School of Medicine at Mount Sinai

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