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Pilot and Translational Study of Dasatinib (NSC#732517) Paclitaxel and Carboplatin in Women With Advanced Stage and Recurrent Endometrial Cancer

18 Years
Open (Enrolling)
Endometrial Adenocarcinoma, Endometrial Adenosquamous Cell Carcinoma, Endometrial Clear Cell Carcinoma, Endometrial Papillary Serous Carcinoma, Recurrent Endometrial Carcinoma, Stage III Endometrial Carcinoma, Stage IV Endometrial Carcinoma

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Trial Information

Pilot and Translational Study of Dasatinib (NSC#732517) Paclitaxel and Carboplatin in Women With Advanced Stage and Recurrent Endometrial Cancer


I. To determine the impact of dasatinib on EphA2 expression in tissue biopsies from patients
with previously untreated, advanced-staged, measurable primary or recurrent endometrial


I. To determine the frequency and severity of adverse events as assessed by CTCAE v. 4 of
dasatinib administered in combination with paclitaxel and carboplatin in patients with
advanced-staged measurable primary or recurrent endometrial cancer.

II. To record the objective response rate by RECIST v.1.1. III. To describe the
progression-free survival (PFS) and overall survival (OS).


I. To explore the relationship of miR520d-3p and EphA2 in pretreatment biopsies.

II. To evaluate downstream EphA2 signaling effectors, such as FAK, paxillin, and p130cas in
pre- and post-tissue treatment biopsies.

III. To explore the effect of dasatinib on the expression of other Eph family members such
as EphB2 and EphB4.

IV. To quantify circulating tumor cells (CTCs) before and during the individual treatment


Patients receive induction therapy comprising dasatinib orally (PO) once daily (QD) for 14
days. *Beginning 7 days later, patients receive paclitaxel IV over 3 hours and carboplatin
IV on day 1, and dasatinib PO QD on days 1-21. Treatment repeats every 21 days for up to 6
courses in the absence of disease progression or unacceptable toxicity.

NOTE: * Patients who have had prior external-beam pelvic or extended-field
pelvic/para-aortic radiation therapy must receive treatment at a reduced dose.

Blood samples are collected at baseline and periodically during treatment for correlative
studies. Patients also undergo tumor tissue biopsy for EphA2 expression analysis and other
correlative studies.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Inclusion Criteria:

- Patients must have measurable stage III, stage IV, or recurrent endometrial carcinoma
whose potential for cure by surgery or radiation therapy alone is poor

- Patients with the following histologic epithelial cell types are eligible:
endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, clear
cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise
specified (N.O.S.), mucinous adenocarcinoma, squamous cell, transitional cell
carcinoma, and mesonephric carcinoma

- Uterine carcinosarcoma and other sarcomas of the uterus will be excluded

- All patients must have measurable disease defined as at least one lesion that can be
accurately measured in at least one dimension (longest dimension to be recorded)

- Each lesion must be ≥ 20 mm when measured by conventional techniques, including
palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging
(MRI), or ≥ 10 mm when measured by spiral CT

- Measurable disease lesions must be amenable to pre- and post-treatment biopsy

- Patients must have at least one "target lesion" to be used to assess response on this
protocol as defined by RECIST

- Tumors within a previously irradiated field will be designated as "non-target"
lesions unless progression is documented or a biopsy is obtained to confirm
persistence at least 90 days following completion of radiation therapy

- No patients who have isolated recurrences (vaginal, pelvic, or para-aortic) that are
amenable to potentially curative treatment with radiation therapy or surgery

- No patients who have an active pleural or pericardial effusion of any grade

- No patients with history or evidence upon physical examination of CNS disease
(treated or untreated), including primary brain tumor, seizures not controlled with
standard medical therapy, or any known brain metastases

- GOG performance status of 0 to 2

- Patients should be free of active infection requiring antibiotics (with the exception
of uncomplicated urinary tract infection [UTI])

- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL

- Platelets greater than or equal to 100,000/mcL

- Creatinine less than or equal to 1.5 times institutional upper limit normal (ULN)

- Bilirubin less than or equal to 1.5 times ULN

- SGOT and alkaline phosphatase less than or equal to 2.5 times ULN

- PT such that international normalized ratio (INR) is ≤ 1.5 (or an in-range INR,
usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin)
and a PTT ≤ 1.5 times the ULN

- Patients receiving low-molecular weight heparin for the prevention or treatment
of venous thromboembolic disease are eligible if considered clinically stable on
their regimen

- Neuropathy (sensory and motor) less than or equal to CTCAE v4 grade 1

- Oxygen saturation greater than or equal to 88% on room air

- Patients must have a baseline electrocardiogram(EKG) performed prior to enrolling on
study; the EKG must have QTc < 450 msec and must not show evidence of serious
ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation must be
less than 3 beats in a row)

- Cardiac ejection fraction must be within the institutional range of normal as
measured by left ventricular ejection fraction (LVEF) testing

- Patients of childbearing potential must have a negative serum pregnancy test prior to
study entry and be practicing an effective form of contraception during the study and
for at least 6 months after receiving the final treatment of dasatinib

- Patients must be able to swallow whole tablets

- No patients with serious, non-healing wound, ulcer, or bone fracture, including
history of abdominal fistula or gastrointestinal perforation

- Patients with an intra-abdominal abscess within 28 days prior to the first date
of dasatinib therapy are ineligible

- No patients with active bleeding or pathologic conditions that carry high risk of
bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
vessels including:

- Bleeding diathesis, congenital or acquired within one year prior to initiating
protocol therapy (e.g., von Willebrand disease, acquired anti-factor VIII

- Significant gastrointestinal (GI) bleeding within three months prior to
initiating protocol therapy

- No patients with clinically significant cardiovascular disease including:

- Uncontrolled hypertension, defined as systolic > 140 mmHg or diastolic > 90 mm

- Myocardial infarction or unstable angina within 6 months of the first date of
dasatinib therapy

- New York Heart Association (NYHA) class II or greater congestive heart failure
or serious cardiac arrhythmia requiring medication; this would include women
with atrial fibrillation, who require rate-controlling medication

- CTCAE v.4 grade 2 or greater peripheral vascular disease

- History of cerebrovascular accident (CVA, stroke), transient ischemic attack
(TIA), or subarachnoid hemorrhage within six months of the first date of
dasatinib therapy

- Patients with hypokalemia or hypomagnesemia if it cannot be corrected to within
normal limits prior to dasatinib treatment

- Required use of a concomitant medication that can prolong the QT interval

- No patients who are pregnant or nursing

- HIV-positive patients on combination antiretroviral therapy are ineligible

- Recovered from effects of recent surgery, radiotherapy, or chemotherapy

- Any hormonal therapy directed at the malignant tumor must be discontinued at least
one week prior to registration

- Any other prior therapy directed at the malignant tumor, including immunologic
agents, must be discontinued at least three weeks prior to registration

- Patients should have had NO prior chemotherapy agents for advanced or recurrent
endometrial cancer

- Prior chemotherapy administration in conjunction with primary radiation therapy
as a radiosensitizer would not exclude a patient from participation in this

- Patients who received adjuvant chemotherapy must be disease-free for at least 6

- Warfarin is permitted for prophylaxis or treatment of thrombosis

- Low-molecular weight heparin is permitted provided the patient's PT/INR is ≤ 1.5

- Patients may have received prior radiation therapy for treatment of endometrial

- Prior radiation therapy may have included pelvic radiation therapy,
extended-field pelvic/para-aortic radiation therapy, and/or intravaginal
brachytherapy, alone or with chemotherapy as a radiation sensitizer

- All radiation therapy must be completed at least 4 weeks prior to the first date
of study therapy

- Patients may have received prior hormonal therapy for treatment of endometrial

- All hormonal therapy must be discontinued at least one week prior to the first
date of study therapy

- No patients who have previously received dasatinib

- Patients may not be receiving any other investigational agents

- Patients cannot take St. John wort or drink grapefruit juice while on study treatment
(discontinue St. John wort at least five days before starting dasatinib)

- Patients receiving IV bisphosphonates agree that IV bisphosphonates will be withheld
for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia, and may be
restarted only if any hypocalcemia has been corrected

- Patients may not be receiving any prohibited potent CYP3A4 inhibitors; for these
drugs, a washout period of greater than or equal to 7 days is required prior to
starting dasatinib treatment

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Change in EphA2 expression

Outcome Description:

Summary statistics and box plots will be used to describe the distributions of expression of EphA2 and its downstream signaling effectors.

Outcome Time Frame:

From baseline to up to day 14

Safety Issue:


Principal Investigator

Robert Coleman

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2011

Completion Date:

Related Keywords:

  • Endometrial Adenocarcinoma
  • Endometrial Adenosquamous Cell Carcinoma
  • Endometrial Clear Cell Carcinoma
  • Endometrial Papillary Serous Carcinoma
  • Recurrent Endometrial Carcinoma
  • Stage III Endometrial Carcinoma
  • Stage IV Endometrial Carcinoma
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Carcinoma
  • Endometrial Neoplasms
  • Carcinoma, Adenosquamous
  • Adenocarcinoma, Clear Cell
  • Adenomyoepithelioma
  • Cystadenocarcinoma, Serous
  • Adenoma



M D Anderson Cancer CenterHouston, Texas  77030