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Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

Primary Purpose

Endometrial Adenocarcinoma, Endometrial Clear Cell Adenocarcinoma, Endometrial Mucinous Adenocarcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Carboplatin
Dasatinib
Laboratory Biomarker Analysis
Paclitaxel
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Endometrial Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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 are not eligible for either COHORT
  • All patients must have measurable disease; measurable disease is 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
  • Patients must have a Gynecologic Oncology Group (GOG) performance status of 0 to 2
  • Recovery from effects of recent surgery, radiotherapy, or chemotherapy
  • Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
  • 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 trial
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL, equivalent to Common Terminology Criteria (CTCAE version [v]4) grade 1
  • Platelets greater than or equal to 100,000/mcL
  • Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v4 grade 1
  • Bilirubin less than or equal to 1.5 x ULN (CTCAE v4 grade 1)
  • Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5 x ULN (CTCAE v4 grade 1)
  • Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v4 grade 1)
  • Neuropathy (sensory and motor) less than or equal to CTCAE v4 grade 1
  • Therapeutic anticoagulation is not contraindicated, but for those patients on therapeutic anticoagulation, alteration in coagulation parameters is expected following initiation of dasatinib; for patients on therapeutic anticoagulation, coagulation parameters should be assessed weekly for the first cycle following initiation of dasatinib, weekly for the first cycle following a dose reduction, and weekly for a minimum of two weeks after stopping dasatinib
  • Warfarin is permitted for prophylaxis or treatment of thrombosis; Note: low-molecular weight heparin is permitted provided the patient's prothrombin time (PT)/international normalized ratio (INR) is =< 1.5; for patients on anticoagulation, coagulation parameters should be assessed weekly for the first cycle following initiation of dasatinib, weekly for the first cycle following a dose reduction, and weekly for a minimum of two weeks after stopping dasatinib
  • PT such that 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 partial thromboplastin time (PTT) =< 1.5 times the institutional upper limit of normal; patients receiving low-molecular weight heparin for the prevention or treatment of venous thromboembolic disease are eligible if considered clinically stable on their regimen
  • Oxygen saturation greater than or equal to 88% on room air (CTCAE 4 < grade 2)
  • Patients must have a baseline electrocardiogram (EKG) performed prior to enrolling on study; the EKG must have corrected QT interval (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; note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution
  • Patients must have signed an approved informed consent
  • 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
  • Patients may not have any clinically significant cardiovascular disease including the following:

    • Myocardial infarction or ventricular tachyarrhythmia within 6 months
    • Prolonged QTc >= 480 msec (Fridericia correction)
    • Ejection fraction less than institutional normal
    • Major conduction abnormality (unless a cardiac pacemaker is present)
    • Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation; the patient may be referred to a cardiologist at the discretion of the principal investigator; patients with underlying cardiopulmonary dysfunction should be excluded from the study

Exclusion Criteria:

  • Patients who have isolated recurrences (vaginal, pelvic, or para-aortic) that are amenable to potentially curative treatment with radiation therapy or surgery
  • Patients who have had a prior chemotherapy regimen for advanced or metastatic disease are excluded; patients who received adjuvant chemotherapy must be disease-free for at least 6 months
  • Patients may have received prior radiation therapy for treatment of endometrial carcinoma; 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; the prior radiation field, radiation dose, number of fractions and prior radiation start and stop dates must be provided at registration
  • Patients who have previously received dasatinib; additionally, patients may not be receiving any other investigational agents; patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least one week prior to the first date of study therapy; patients with known brain metastases should be excluded from this clinical trial
  • Patients with serious, non-healing wound, ulcer, or bone fracture; this includes 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
  • Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels; patients who have a history of significant bleeding disorder unrelated to cancer including:

    • Bleeding diathesis, congenital or acquired within one year prior to initiating protocol therapy (e.g. von Willebrand's disease, acquired anti-factor VIII antibodies); significant gastrointestinal (GI) bleeding within three months prior to initiating protocol therapy
  • Patients with history or evidence upon physical examination of central nervous system (CNS) disease (treated or untreated), including primary brain tumor, seizures not controlled with standard medical therapy, or any brain metastases
  • Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events (CTCAE v4 grade 2 or greater, excluding alopecia) due to agents administered more than 4 weeks earlier
  • Patients cannot take St. John's wort or drink grapefruit juice while on study treatment (discontinue St. John wort at least five days before starting dasatinib)
  • Patients who have an active pleural or pericardial effusion of any grade
  • 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 with clinically significant cardiovascular disease; this includes:

    • Uncontrolled hypertension, defined as systolic > 140 mmHg or diastolic > 90 mm Hg
    • 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 v4 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
  • Patients may not be receiving any prohibited potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors; for these drugs, a washout period of greater than or equal to 7 days is required prior to starting dasatinib treatment
  • The concomitant use of histamine (H2) blockers and proton pump inhibitors (PPI's) with dasatinib is not recommended (e.g., famotidine, omeprazole); the use of antacids should be considered in place of H2 blockers or PPIs in patients receiving dasatinib therapy; if antacid therapy is needed, the antacid dose should be administered two hours before or after the dose of dasatinib
  • Patients may not be receiving any other investigational agents
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients who are pregnant or nursing; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Uterine carcinosarcoma and other sarcomas of the uterus will be excluded

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (dasatinib, paclitaxel, carboplatin)

Arm Description

Patients receive induction therapy comprising dasatinib PO 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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Response rate (complete [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors version 1.1
Best overall response will be tabulated. The proportion of patients with CR and with (CR+PR) will be estimated with 95% confidence intervals.
Progression free survival
Estimated with the product-limit estimator of Kaplan and Meier and illustrated with Kaplan-Meier plots.
Overall survival
Estimated with the product-limit estimator of Kaplan and Meier and illustrated with Kaplan-Meier plots.
Numbers of circulating tumor cells (CTCs)
Descriptive statistics will be used to summarize the number of CTCs for patients with each type of response. Estimate the mean number of CTCs for each of these groups with 95% confidence intervals.
Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4
Tabulated by grade and relationship to study drug, stratified by whether or not patients had prior pelvic radiation.

Full Information

First Posted
September 24, 2011
Last Updated
April 4, 2018
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01440998
Brief Title
Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer
Official Title
Pilot and Translational Study of Dasatinib (NSC#732517) Paclitaxel and Carboplatin in Women With Advanced Stage and Recurrent Endometrial Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
September 20, 2011 (Actual)
Primary Completion Date
December 31, 2015 (Actual)
Study Completion Date
December 31, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This pilot phase I trial studies how well dasatinib works together with paclitaxel and carboplatin in treating patients with stage III, stage IV, or endometrial cancer that has come back after a period of improvement. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving dasatinib together with paclitaxel and carboplatin may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate pMEK and EphA2 signaling effectors in pre- and post- treatment biopsy tissues from patients with advanced staged measurable primary or recurrent endometrial cancer. SECONDARY OBJECTIVES: I. To determine the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4 (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 Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. III. To describe the progression-free survival and overall survival. TERTIARY OBJECTIVES: I. To explore the relationship of micro ribonucleic acid (RNA) 520d-3p (miR520d-3p) and EphA2 in pretreatment biopsies. II. To evaluate downstream EphA2 signaling effectors, such as CAV-1, pAKT, 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 phases. OUTLINE: Patients receive induction therapy comprising dasatinib orally (PO) once daily (QD) for 14 days. *Beginning 7 days later, patients receive paclitaxel intravenously (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. After completion of study treatment, patients are followed up every 3 months for 1 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometrial Adenocarcinoma, Endometrial Clear Cell Adenocarcinoma, Endometrial Mucinous Adenocarcinoma, Endometrial Serous Adenocarcinoma, Endometrial Squamous Cell Carcinoma, Endometrial Transitional Cell Carcinoma, Endometrial Undifferentiated Carcinoma, Endometrioid Adenocarcinoma, Recurrent Uterine Corpus Carcinoma, Stage III Uterine Corpus Cancer AJCC v7, Stage IIIA Uterine Corpus Cancer AJCC v7, Stage IIIB Uterine Corpus Cancer AJCC v7, Stage IIIC Uterine Corpus Cancer AJCC v7, Stage IV Uterine Corpus Cancer AJCC v7, Stage IVA Uterine Corpus Cancer AJCC v7, Stage IVB Uterine Corpus Cancer AJCC v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (dasatinib, paclitaxel, carboplatin)
Arm Type
Experimental
Arm Description
Patients receive induction therapy comprising dasatinib PO 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.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Other Intervention Name(s)
BMS-354825, Sprycel
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Change in pMEK expression
Description
Change in pMEK expression will be evaluated.
Time Frame
Up to 1 year
Title
Change in EphA2 expression
Description
Summary statistics and box plots will be used to describe the distributions of expression of EphA2 and its downstream signaling effectors.
Time Frame
From baseline to up to day 14
Secondary Outcome Measure Information:
Title
Response rate (complete [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors version 1.1
Description
Best overall response will be tabulated. The proportion of patients with CR and with (CR+PR) will be estimated with 95% confidence intervals.
Time Frame
Up to 1 year
Title
Progression free survival
Description
Estimated with the product-limit estimator of Kaplan and Meier and illustrated with Kaplan-Meier plots.
Time Frame
From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year
Title
Overall survival
Description
Estimated with the product-limit estimator of Kaplan and Meier and illustrated with Kaplan-Meier plots.
Time Frame
From start of treatment to time of death, assessed up to 1 year
Title
Numbers of circulating tumor cells (CTCs)
Description
Descriptive statistics will be used to summarize the number of CTCs for patients with each type of response. Estimate the mean number of CTCs for each of these groups with 95% confidence intervals.
Time Frame
Up to 1 year
Title
Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4
Description
Tabulated by grade and relationship to study drug, stratified by whether or not patients had prior pelvic radiation.
Time Frame
Up to 1 year

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 are not eligible for either COHORT All patients must have measurable disease; measurable disease is 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 Patients must have a Gynecologic Oncology Group (GOG) performance status of 0 to 2 Recovery from effects of recent surgery, radiotherapy, or chemotherapy Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI]) 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 trial Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL, equivalent to Common Terminology Criteria (CTCAE version [v]4) grade 1 Platelets greater than or equal to 100,000/mcL Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v4 grade 1 Bilirubin less than or equal to 1.5 x ULN (CTCAE v4 grade 1) Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5 x ULN (CTCAE v4 grade 1) Alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v4 grade 1) Neuropathy (sensory and motor) less than or equal to CTCAE v4 grade 1 Therapeutic anticoagulation is not contraindicated, but for those patients on therapeutic anticoagulation, alteration in coagulation parameters is expected following initiation of dasatinib; for patients on therapeutic anticoagulation, coagulation parameters should be assessed weekly for the first cycle following initiation of dasatinib, weekly for the first cycle following a dose reduction, and weekly for a minimum of two weeks after stopping dasatinib Warfarin is permitted for prophylaxis or treatment of thrombosis; Note: low-molecular weight heparin is permitted provided the patient's prothrombin time (PT)/international normalized ratio (INR) is =< 1.5; for patients on anticoagulation, coagulation parameters should be assessed weekly for the first cycle following initiation of dasatinib, weekly for the first cycle following a dose reduction, and weekly for a minimum of two weeks after stopping dasatinib PT such that 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 partial thromboplastin time (PTT) =< 1.5 times the institutional upper limit of normal; patients receiving low-molecular weight heparin for the prevention or treatment of venous thromboembolic disease are eligible if considered clinically stable on their regimen Oxygen saturation greater than or equal to 88% on room air (CTCAE 4 < grade 2) Patients must have a baseline electrocardiogram (EKG) performed prior to enrolling on study; the EKG must have corrected QT interval (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; note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution Patients must have signed an approved informed consent 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 Patients may not have any clinically significant cardiovascular disease including the following: Myocardial infarction or ventricular tachyarrhythmia within 6 months Prolonged QTc >= 480 msec (Fridericia correction) Ejection fraction less than institutional normal Major conduction abnormality (unless a cardiac pacemaker is present) Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation; the patient may be referred to a cardiologist at the discretion of the principal investigator; patients with underlying cardiopulmonary dysfunction should be excluded from the study Exclusion Criteria: Patients who have isolated recurrences (vaginal, pelvic, or para-aortic) that are amenable to potentially curative treatment with radiation therapy or surgery Patients who have had a prior chemotherapy regimen for advanced or metastatic disease are excluded; patients who received adjuvant chemotherapy must be disease-free for at least 6 months Patients may have received prior radiation therapy for treatment of endometrial carcinoma; 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; the prior radiation field, radiation dose, number of fractions and prior radiation start and stop dates must be provided at registration Patients who have previously received dasatinib; additionally, patients may not be receiving any other investigational agents; patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least one week prior to the first date of study therapy; patients with known brain metastases should be excluded from this clinical trial Patients with serious, non-healing wound, ulcer, or bone fracture; this includes 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 Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels; patients who have a history of significant bleeding disorder unrelated to cancer including: Bleeding diathesis, congenital or acquired within one year prior to initiating protocol therapy (e.g. von Willebrand's disease, acquired anti-factor VIII antibodies); significant gastrointestinal (GI) bleeding within three months prior to initiating protocol therapy Patients with history or evidence upon physical examination of central nervous system (CNS) disease (treated or untreated), including primary brain tumor, seizures not controlled with standard medical therapy, or any brain metastases Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events (CTCAE v4 grade 2 or greater, excluding alopecia) due to agents administered more than 4 weeks earlier Patients cannot take St. John's wort or drink grapefruit juice while on study treatment (discontinue St. John wort at least five days before starting dasatinib) Patients who have an active pleural or pericardial effusion of any grade 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 with clinically significant cardiovascular disease; this includes: Uncontrolled hypertension, defined as systolic > 140 mmHg or diastolic > 90 mm Hg 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 v4 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 Patients may not be receiving any prohibited potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors; for these drugs, a washout period of greater than or equal to 7 days is required prior to starting dasatinib treatment The concomitant use of histamine (H2) blockers and proton pump inhibitors (PPI's) with dasatinib is not recommended (e.g., famotidine, omeprazole); the use of antacids should be considered in place of H2 blockers or PPIs in patients receiving dasatinib therapy; if antacid therapy is needed, the antacid dose should be administered two hours before or after the dose of dasatinib Patients may not be receiving any other investigational agents Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible Patients who are pregnant or nursing; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Uterine carcinosarcoma and other sarcomas of the uterus will be excluded
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Coleman
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

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