Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Pleural Effusion

Lung Neoplasms

Pleural Effusion, Malignant

Lung Diseases

Pleural Diseases

Pleural Neoplasms

Respiratory Tract Diseases

Thoracic Neoplasms

Respiratory Tract Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Mitogens

Dasatinib

Afatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Dose escalation followed by dose expansion. Escalation cohort: Afatinib and Dasatinib. This study is divided into two parts. The first 8 - 18 people will be entered in the first part, called Phase 1A. Then this part will end.

Expansion cohort:: Afatinib and Dasatinib. The next 20 people will enter into the second part, called Phase 1B.

1A: Begins Day 8. Level 1 - 100 mg, Level 2 - 100 mg, Level 3 - 140 mg.

Dasatinib - 1A

1A: Begins Day 1. Level 1 - 30 mg, Level 2 - 40 mg, Level 3 - 40 mg.

Afatinib - 1A

In Phase 1B, a mutationally selected 20 participants (total) will be treated at the recommended dose to confirm tolerability and evaluate for early response signal.

Dasatinib - 1B

Afatinib - 1B

Ben Creelan, M.D.

The purpose of this study is to:

* Find out if the study drugs Afatinib and Dasatinib can be safely given together to patients with lung cancer
* Learn how these two drugs work in cancer cells when they are combined
* Learn more about the side effects of these two drugs when combined
* Find the highest doses of the study drugs Afatinib and Dasatinib that can be given safely without causing serious side effects

Phase I Trial of Afatinib (BIBW 2992) and Dasatinib in Non-small Cell Lung Cancer (NSCLC)

Phase I Trial Evaluating Safety and Tolerability of the Irreversible Epidermal Growth Factor Receptor Inhibitor Afatinib (BIBW 2992) in Combination With the SRC Kinase Inhibitor Dasatinib for Patients With Non-small Cell Lung Cancer (NSCLC)

The MTD for this combined treatment will be defined as either:

1. The highest dosage cohort in which six patients had been treated and there were less than two dose limiting toxicities (DLTs) or,
2. Afatinib at the highest tolerated dose investigated (40 mg by mouth \[PO\] daily) plus dasatinib at the highest tolerated dose investigated (cohort 3, 140 mg PO daily).

Estimates objective response rate (complete response \[CR\] and partial response \[PR\]) in participants with acquired EGFR resistance

Estimate the 6-month progression free survival (PFS) rate in participants with acquired EGFR resistance. Response Criteria for Phase 1B will follow RECIST v.1.1: Progressive Disease (PD) is defined as at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Boehringer Ingelheim

Bristol-Myers Squibb

H. Lee Moffitt Cancer Center and Research Institute

Participants were given 30 mg Afatinib and 100 mg Dasatinib

Part 1A Level 1

Participants were given 40 mg Afatinib and 100 mg Dasatinib

Part 1A Level 2

Participants given Afatinib 30 mg and 100 mg Dasatinib

Part 1B

All Participants Who Received Study Treatment

All Participants

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Thoracic CRO, attn: Dr. Ben Creelan

Dasatinib daily

Dose Escalation and Expansion

All participants who received at least one dose of Afatinib and Dasatinib.

Maximum Tolerated Dose (MTD) of Afatinib (BIBW 2992) in Combination With Dasatinib

Number of Participants With Objective Response

Median Progression Free Survival

Participants given 30 mg Afatinib and 100 mg Dasatinib

Participants given 40 mg Afatinib and 100 mg Dasatinib

Overall Study

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Digestive System Diseases

Gland and Hormone Related Diseases

Nervous System Diseases

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Immune System Diseases

Rare Diseases

Breast Neoplasms

Syndrome

Pancreatic Neoplasms

Melanoma

Pancreatitis

Pancreatitis, Chronic

Ataxia

Cerebellar Ataxia

Telangiectasis

Ataxia Telangiectasia

Peutz-Jeghers Syndrome

Nevus

Colorectal Neoplasms

Colorectal Neoplasms, Hereditary Nonpolyposis

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Intestinal Neoplasms

Neoplastic Syndromes, Hereditary

Colonic Diseases

Intestinal Diseases

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

Intestinal Polyposis

Lentigo

Melanosis

Hyperpigmentation

Pigmentation Disorders

Skin Diseases

Pancreatic Cancer

Hereditary Pancreatitis

Gastrointestinal Agents

Pancrelipase

Pancreatin

Secretin

Hormones

Hormone Antagonists

Serine

High Risk Group 2 (familial pancreatic cancer relatives):

1. \> 55 years old or 10 years younger than the age of youngest relative with pancreatic cancer, and
2. come from a family with 2 or more members with a history of pancreatic cancer (2 of which have a first-degree relationship consistent with familial pancreatic cancer), and
3. have a first-degree relationship with at least one of the relatives with pancreatic cancer.

If there are 2 or more affected blood relatives, at least 1 must be a first-degree relative of the individual being screened

High Risk Group 3 (Group 1 germline mutation carriers with an associated with an estimated lifetime risk of pancreatic cancer of \~10% or higher):

a. \> 50 years old or 10 years younger than the age of the youngest relative affected, if pancreatic cancer is in family, and b. The Patient is a carrier of a confirmed BRCA2, ATM or PALB2 mutation, regardless of family history of pancreatic cancer. b.\> Individual is a carrier of a confirmed FAMMM (p16/CDKN2A) mutation, age 40 years or older, regardless of family history of pancreas cancer.

High Risk Group 4 (Group 2 germline mutation carriers with an associated with an estimated lifetime risk of pancreatic cancer of \~5%):

1. \> 50 years old or 10 years younger than the age of the youngest relative with pancreatic cancer, and
2. The patient is a carrier of a confirmed BRCA1 or HNPCC (hereditary non-polyposis colorectal cancer or Lynch syndrome, hMLH1, hMSH2, PMS1, hMSH6, EpCAM) gene mutation, and there is \> 1 pancreatic cancer in the family, one of whom is a first- or second-degree relative of the subject to be screened.

High risk group 5 (hereditary pancreatitis) with confirmed gene mutations that predispose to chronic pancreatitis, such as PRSS1, PRSS2, CTRC) and age 50 years or older (these patients have an estimated lifetime risk for pancreatic cancer of 40%) or twenty-years since their first attack of pancreatitis, whichever age is younger.

1. At least 30 years old, and
2. at least 2 of 3 criteria diagnostic of Peutz-Jeghers syndrome (characteristic intestinal hamartomatous polyps, mucocutaneous melanin deposition, or family history of Peutz-Jeghers syndrome), or,
3. known STK11 gene mutation carrier

1. are undergoing routine EGD or Colonoscopy; or Endoscopic Ultrasound (EUS) and/or Endoscopic Retrograde Cholangiopancreatography (ERCP) for non-pancreatic indications as part of their standard medical care, and
2. have no clinical or radiologic suspicion of pancreatic disease (chronic pancreatitis or pancreatic cancer)

1. are undergoing EUS and/or ERCP for evaluation and/or treatment of suspected or proven chronic pancreatitis as part of their standard medical care, and,
2. have no clinical or radiologic suspicion of pancreatic cancer

a. are undergoing EUS and/or ERCP for evaluation and/or treatment of suspected or proven pancreatic ductal adenocarcinoma (based on clinical and radiologic evidence)

are undergoing EUS and/or ERCP for evaluation and/or treatment of suspected or proven pancreatic cancer precursor, intraductal papillary mucinous neoplasm (based on clinical presentation and radiologic or prior EUS or radiologic evidence of a dilated main pancreatic duct and/or pancreatic cystic lesion communicating with the pancreatic ductal system).

inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.

MRI abdomen with contrast (MRCP) will be clinically indicated for abnormal novel CA-19-9 lab results.

A tumor marker gene test that will be used to stratify individuals into one of several circulating tumor marker reference ranges for CA19-9. The variants in the genes FUT3 and FUT2 affect the levels of CA19-9.

Tumor marker gene test with CA19-9

Hilary Cosby, RN

Scott Merenda, BSN

James Farrell, MD

Hilary Cosby, RN, CGRN

Michael Goggins, MD

Marcia I Canto, MD

Emily Blair

Chinedu Ukaegbu

Sapna Syngal, MD

Erika Koeppe, MS

Elena Stoffel, MD

Tiffany Lam

Fay Kastrinos, MD

Barbara Heaton

Wendy Brock, RN

Amitabh Chak, MD

Maureen DeMarshall, RN

Daniel Clay

Bryson Katona, MD

Christine Decapite

Sara Booz

Randall Brand, MD

Johns Hopkins clinical research office quality assurance group will monitor and audit this study at Johns Hopkins. The Sub Investigator at each site will be responsible for internal monitoring at their site.

The Sub Investigator at each site will be responsible for internal monitoring at their site. The site sub Investigator and study team will report any serious adverse events to Principal Investigator and annually report adverse events.

Evaluation of the effect of diagnostic tests for pancreatic cancer

No masking of the diagnostic test results

The Cancer of the Pancreas Screening-5 CAPS5)Study

Aim #3: To determine the prevalence of pancreatic lesions, pancreatic fluid mutations and circulating pancreatic epithelial cells among a large cohort of high-risk individuals undergoing pancreatic screening and surveillance of a new cohort in which screening is begun at age \>55.

Aim #4 To evaluate the diagnostic performance of a tumor marker gene test to personalize the normal reference range of tumor markers such as CA19-9 for patients undergoing pancreatic surveillance.

Aim #1: To evaluate pancreatic fluid mutations and circulating pancreatic epithelial cells as accurate markers of neoplasia by comparing their prevalence in cases with sporadic pancreatic neoplasia to healthy and disease controls.

Aim #2: To compare the prevalence of pancreatic fluid mutations and circulating pancreatic epithelial cells among a prospective cohort of individuals with sporadic pancreatic cysts undergoing pancreatic surveillance.

ChiRhoClin, Inc.

National Cancer Institute (NCI)

National Institutes of Health (NIH)

Johns Hopkins University

Recurrence

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasm Metastasis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Metastatic Squamous Neck Cancer With Occult Primary

SF1126 1110 mg/m2 administered intravenously (IV) twice per week (separated by at least three days) for the first four treatment cycles (28 days) and then once weekly for subsequent cycles.

SF1126

Ezra Cohen, MD

The purpose of this study is to test the good and bad effects of an experimental drug called SF1126. This drug is being tested in patients whose cancer has not been controlled by available standard therapies and who have certain genes in their tumor.

SF1126 is a drug that inhibits a cell protein called phosphatidyl inositol 3 kinase (PI3K). PI3K is part of signaling pathway that tells cancer cells to grow, survive, invade and metastasize. PI3K also has an important role in the development of blood vessels that are required to support tumor growth. SF1126 is being developed by SignalRx Pharmaceuticals, Inc. It is considered an experimental drug because it is not approved by the FDA for any disease treatment.

SignalRx Pharmaceuticals has developed a pan isoform specific PI-3 inhibitor called SF1126 to treat patients with advanced or metastatic cancer. SF1126 is a conjugate that contains two components: SF1101 (the active drug) and SF1174 (an inactive tetrapeptide RGD targeting moiety)

Both components of SF1126 play key roles in the activity of the drug. SF1101 is a selective inhibitor of certain members of the phosphatidyl inositol 3-kinase (PI-3) family and SF1174 binds selectively to receptors known to be present on neovasculature supporting tumors and on some tumor cells themselves. These components result in a drug designed to be both selective in its activity and targeted in its delivery.

This is an open label Phase II study of SF1126 in adult patients with recurrent or refractory advanced SCCHN with PIK3CA mutation. Treatment cycles (28 days) will consist of SF1126 1110 mg/m2 administered intravenously (IV) twice per week (separated by at least three days) for the first four cycles and then once weekly for subsequent cycles.

SF1126 in Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes

A Phase II Open Label Study of the PI3 Kinase (PI-3) Inhibitor, SF1126, in Patients With Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes

best response of PR or CR observed within 6 months of enrollment

SignalRX Pharmaceuticals, Inc.

Ezra Cohen

Professor

SF1126 1110 mg/m2 administered intravenously (IV) twice per week (separated by at least three days) for the first four treatment cycles (28 days) and then once weekly for subsequent cycles.

SF1126

To Determine ORR

Number of Participants With Treatment-related Adverse Events

To Assess the Effect of SF1126 on Time to Progression.

To Assess the Effect of SF1126 on Overall Survival.

To Assess Disease-related Patient-reported Outcomes Using the EORTC-QLQ-

Have a diagnosis of cancer of any type. Have an EGFR T790M mutation identified on either genotyping of their cancer at diagnosis OR on quantitative plasma genotyping with evidence of high level (\>40% allelic fraction) EGFR T790M. OR another EGFR mutation previously reported as germline detected on tumor genotyping of their cancer.

Have a relative known to carry a germline EGFR mutation (either T790M or other novel germline EGFR mutation)

Have a known germline EGFR mutation (either T790M or other novel germline EGFR mutation)

Jaclyn LoPiccolo, MD

Lung cancer is a common malignancy that is associated with cigarette smoking but can also affect individuals who never smoked. It is not well understood whether there are hereditary risk factors that influence the risk of lung cancer.

It has been recently found that a small number of families have an inherited (passed from parent to child) change in one of their genes that may contribute to an increased tendency to develop lung cancers, even in never smokers. In some lung cancer patients this gene, called "EGFR", contains a DNA change known as an "inherited EGFR mutation". Early data indicate that these inherited EGFR mutations may be associated with an increased risk of lung cancer.

So far, only a small number of families have been found to carry inherited EGFR mutations. For this reason the risk of lung cancer associated with inherited EGFR mutations is not well understood. Understanding the risk may help investigators find ways of detecting lung cancer sooner or reducing the risk of developing lung cancer.

It was recently discovered that lung cancer patients who are found to carry one rare EGFR mutation in their cancer cells, called "T790M", have an increased risk of carrying an inherited EGFR mutation in their normal cells as well. This represents a new strategy for finding individuals and families carrying inherited EGFR mutations.

This research study is designed to find cancer patients whose tumors have this EGFR mutation, T790M, to find out if they also have an inherited EGFR mutation. Subjects will not have to undergo a biopsy to participate in this research study. Investigators will collect a saliva specimen from patients with a T790M in their cancer to find out if they also have an inherited EGFR mutation.

Study participants found or known to carry an inherited EGFR mutation will have the option of offering their close relative the opportunity to also participate in this study. Close relatives can consider testing to see if they also carry the inherited mutation in their normal cells. Once investigators have identified individuals and relatives that carry inherited EGFR mutations in their genes, investigators will then try to understand the risk of lung cancer and other cancers. Individuals with inherited EGFR mutations will also have the opportunity to participate in future studies related to cancer and other diseases.

This study is being funded in part by the Conquer Cancer Foundation of ASCO and the Bonnie J. Addario Lung Cancer Foundation.

If a subject have lung cancer or another cancer carrying a T790M mutation in the EGFR gene, he/she may be eligible to participate in this research study. To determine eligibility, a subject will need to perform the following steps: provide informed consent, fill out the study questionnaire and provide medical records documentation.

The study questionnaire should take about 30 minutes to complete. The questionnaire asks for information on personal and family cancer and health history. The information provided will help investigators to determine which parts of the study a subject is eligible for. A few weeks after submitting the questionnaire, a member of the research study team will contact the subject by telephone to clarify any questions about the response.

For medical records documentation investigators will request permission to obtain and review medical records pertaining to any personal history of cancer. Subjects will need to complete a medical record release form to allow investigators to collect medical records regarding prior cancers and cancer treatment.

After a subject is determined to be eligible, he/she will have a conversation with a genetic counselor regarding the potential risks, benefits and limitations of genetic testing. A genetic counselor is an expert in the field of inherited disorders. They work as members of the health care team and act as a patient advocate providing education and support to the patient, family and the medical team. If a subject agrees to proceed, he/she will be provided a kit (by mail or in person) to provide a saliva sample for genetic testing. This involves spitting into a special container provided by the study. This sample will be sent to a clinically-certified testing laboratory to determine presence of an inherited EGFR mutation.

Once the results have been determined, the subject will receive a letter with the phone number of a genetic counselor to call in order to review results of the genetic testing. Alternatively, a subject can decide not to receive the results of the genetic testing and can note that on the letter received and send it back to the study team instead of calling for the results.

If a mutation is found in the saliva sample, a subject will receive information about how to undergo confirmatory testing of a blood specimen. This can be done at a local laboratory using a kit that will be mailed. When the results are available a genetic counselor will call to discuss them. If the confirmatory blood test confirms an inherited mutation, subjects will receive instructions on how to invite family members to be tested if appropriate.

Investigators will collect material from a prior tumor biopsy (if available), copies of imaging scans, and medical records to study. The copies of imaging scans will allow study of the characteristics of nodules in the lungs. This information will be used to answer additional questions about cancers carrying EGFR T790M mutations.

It will only take a few months to complete the main part of the study. After that, subjects will be followed every 6 months for 2 years. If a subject allows a piece of a tumor specimen or DNA to be stored for future investigational studies, then he/she will remain enrolled in research for as long as the specimen is stored in the specimen bank.

INHERIT EGFR - Studying Germline EGFR Mutations

INHERIT EGFR - INvestigating HEreditary RIsk From T790M: A Multi-Centered Study to Identify and Characterize Individuals Carrying Germline EGFR Mutations

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Trial of Afatinib (BIBW 2992) and Dasatinib in Non-small Cell Lung Cancer (NSCLC)	NCT01999985	Lung Cancer Non-small Cell ...	Dasatinib - 1A Afatinib - 1A Dasatinib - 1B Afatinib - 1B	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
The Cancer of the Pancreas Screening-5 CAPS5)Study	NCT02000089	Pancreas Cancer Peutz-Jeghers S... Gene Mutation Germline Mutati... Lynch Syndrome	Secretin MRI Tumor marker ge...	18 Years -	Johns Hopkins University
SF1126 in Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes	NCT02644122	Metastatic Squa...	SF1126	18 Years -	University of California, San Diego
INHERIT EGFR - Studying Germline EGFR Mutations	NCT01754025	Lung Cancer		18 Years -	Dana-Farber Cancer Institute
Effects of Different Genetic Mutations on Prognosis in sMPLC Adenocarcinoma Patients	NCT03764371	Gene Mutation	KAPA Hyper Prep...	18 Years - 75 Years	The First Hospital of Jilin University
ZR-CHOP in DLBCL With Specific Gene Abnormality	NCT05290337	Diffuse Large B...	zanubrutinib	18 Years - 75 Years	Fudan University
Multi Parametric Test Predicting the Risk of Colorectal Neoplasia Recurrence	NCT03434925	Colon Cancer	Multi-targeted ...	18 Years - 75 Years	Military University Hospital, Prague
The Cancer of the Pancreas Screening-5 CAPS5)Study	NCT02000089	Pancreas Cancer Peutz-Jeghers S... Gene Mutation Germline Mutati... Lynch Syndrome	Secretin MRI Tumor marker ge...	18 Years -	Johns Hopkins University
Multi Parametric Test Predicting the Risk of Colorectal Neoplasia Recurrence	NCT03434925	Colon Cancer	Multi-targeted ...	18 Years - 75 Years	Military University Hospital, Prague
INHERIT EGFR - Studying Germline EGFR Mutations	NCT01754025	Lung Cancer		18 Years -	Dana-Farber Cancer Institute
SF1126 in Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes	NCT02644122	Metastatic Squa...	SF1126	18 Years -	University of California, San Diego
ZR-CHOP in DLBCL With Specific Gene Abnormality	NCT05290337	Diffuse Large B...	zanubrutinib	18 Years - 75 Years	Fudan University
Phase I Trial of Afatinib (BIBW 2992) and Dasatinib in Non-small Cell Lung Cancer (NSCLC)	NCT01999985	Lung Cancer Non-small Cell ...	Dasatinib - 1A Afatinib - 1A Dasatinib - 1B Afatinib - 1B	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

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