Bristol-Myers Squibb Dasatinib Src Inhibition in Endometrial Cancer

NCT01482728 | Completed Early Phase 1 DMC

• 1 other identifier: 15809
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if the investigators can measure inhibition of a protein, Src (named for Sarcoma), in tissue and blood in patients with a diagnosis of endometrial cancer. Dasatinib is a drug that blocks the activity of an important protein in cancer cells called Src. The investigators can measure the blocking of Src in the bloodstream. However, the investigators do not know if measures in the bloodstream reflect blockage of Src in cancer tissue. The investigators are doing this study to try and see if the investigators can match what the investigators see in cancer tissue to what the investigators see in the bloodstream. the investigators hope that in the future, the investigators can use blood to measure protein inhibition by dasatinib instead of asking patients to undergo repeat biopsies.

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Changes in levels of SFK protein activity in a) endometrial tumor tissue and b) blood induced within two different doses of dasatinib treatment.

  In this study the change in levels of SFK protein activity in both tissue and blood will represent the measured pharmacodynamic response.

  1 year

Secondary Outcomes (1)

• Changes in levels of SFK protein activity in blood correlates with changes in levels of SFK protein activity in endometrial tumor tissue induced by two different doses of dasatinib treatment.

  1 year

Interventions

Dasatinib DRUG

100 mg dasatinib, the day before surgery and the day of surgery

Also known as: Spyricel

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women age 18 and older
• Newly diagnosed primary histologically documented endometrioid adenocarcinoma of the endometrium that is being treated surgically with hysterectomy and BSO
• Performance status 0-1
• Agree to pre operative biopsy
• Adequate organ function
• Ability to take oral medication
• Negative serum pregnancy test

You may not qualify if:

• Prior therapy with dasatinib or any other anti-src drug
• Women with positive pregnancy test
• Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s)
• Prisoners or subjects who are involuntarily incarcerated
• Histologic subtypes of endometrial cancer other than endometrioid
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
• History of significant bleeding disorder unrelated to cancer
• No previous history of malignancy which required radiotherapy or systemic treatment within the past 5 years
• Pleural or pericardial effusion of any grade
• Cardiac symptoms including but not limited to angina, prolonged QTc interval, significant ventricular arrhythmia

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (4)

• Shah YM, Rowan BG. The Src kinase pathway promotes tamoxifen agonist action in Ishikawa endometrial cells through phosphorylation-dependent stabilization of estrogen receptor (alpha) promoter interaction and elevated steroid receptor coactivator 1 activity. Mol Endocrinol. 2005 Mar;19(3):732-48. doi: 10.1210/me.2004-0298. Epub 2004 Nov 4.

  PMID: 15528270 BACKGROUND

• Biscardi JS, Maa MC, Tice DA, Cox ME, Leu TH, Parsons SJ. c-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845 and Tyr1101 is associated with modulation of receptor function. J Biol Chem. 1999 Mar 19;274(12):8335-43. doi: 10.1074/jbc.274.12.8335.

  PMID: 10075741 BACKGROUND

• Desouki MM, Rowan BG. SRC kinase and mitogen-activated protein kinases in the progression from normal to malignant endometrium. Clin Cancer Res. 2004 Jan 15;10(2):546-55. doi: 10.1158/1078-0432.ccr-0661-03.

  PMID: 14760076 BACKGROUND

• Feng W, Webb P, Nguyen P, Liu X, Li J, Karin M, Kushner PJ. Potentiation of estrogen receptor activation function 1 (AF-1) by Src/JNK through a serine 118-independent pathway. Mol Endocrinol. 2001 Jan;15(1):32-45. doi: 10.1210/mend.15.1.0590.

  PMID: 11145737 BACKGROUND

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Linda R Duska, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending

Study Record Dates

• First Submitted: November 14, 2011
• First Posted: November 30, 2011
• Study Start: January 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 13, 2016

Record last verified: 2016-05

Locations

US (1)