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Endometrial AdenocarcinomaPhase 1NCT01440998

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

A Phase 1 study testing Carboplatin, Dasatinib and Laboratory Biomarker Analysis in people with Endometrial Adenocarcinoma and Endometrial Clear Cell Adenocarcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Carboplatin, Dasatinib and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
20 Sep 2011to 31 Dec 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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:
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Carboplatin, Dasatinib, Laboratory Biomarker Analysis, Paclitaxel
Medical subject headings
Carcinoma, Endometrioid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • DasatinibDrug

    Also called BMS-354825, Sprycel

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

Study groups in NCT01440998
Study groupRoleWhat they receive
Treatment (dasatinib, paclitaxel, carboplatin)ExperimentalPatients 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.
Receives: Drug: Carboplatin; Drug: Dasatinib; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in pMEK expression

    Change in pMEK expression will be evaluated.

    Measured: Up to 1 year

  2. 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.

    Measured: From baseline to up to day 14

Secondary outcomes (5)

  1. 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.

    Measured: Up to 1 year

  2. Progression free survival

    Estimated with the product-limit estimator of Kaplan and Meier and illustrated with Kaplan-Meier plots.

    Measured: From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year

  3. Overall survival

    Estimated with the product-limit estimator of Kaplan and Meier and illustrated with Kaplan-Meier plots.

    Measured: From start of treatment to time of death, assessed up to 1 year

  4. 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.

    Measured: Up to 1 year

  5. 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.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2011 (estimated)
  2. Study start20 Sep 2011
  3. Primary completion31 Dec 2015
  4. Study completion31 Dec 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01440998
Sponsor's protocol ID
NCI-2011-03275
Other IDs
NCI-2011-03275, 2011-0252, CDR0000712251, MDA-2011-0252, 8836, 8836, P30CA016672, P50CA098258
Status last verified
Apr 2018
First submitted
24 Sep 2011
Last updated
5 Apr 2018
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Carboplatin, Dasatinib and Laboratory Biomarker Analysis in people with Endometrial Adenocarcinoma and Endometrial Clear Cell Adenocarcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in pMEK expression (time frame: Up to 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01440998.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2018.

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