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

NCT01440998 | Completed Phase 1

• 7 other identifiers: NCI-2011-032752011-0252CDR0000712251MDA-2011-02528836P30CA016672P50CA098258
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Change in pMEK expression

  Change in pMEK expression will be evaluated.

  Up to 1 year

• 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.

  From baseline to up to day 14

Secondary Outcomes (5)

• Response rate (complete [CR] or partial response [PR]) according to Response Evaluation Criteria in Solid Tumors version 1.1

  Up to 1 year

• Progression free survival

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

• Overall survival

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

• Numbers of circulating tumor cells (CTCs)

  Up to 1 year

• Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4

  Up to 1 year

Study Arms (1)

Treatment (dasatinib, paclitaxel, carboplatin)

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Dasatinib; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (dasatinib, paclitaxel, carboplatin)

Dasatinib DRUG

Given PO

Also known as: BMS-354825, Sprycel

Treatment (dasatinib, paclitaxel, carboplatin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (dasatinib, paclitaxel, carboplatin)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (dasatinib, paclitaxel, carboplatin)

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Endometrioid

Interventions

Carboplatin; Dasatinib; Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endometrial Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Ovarian Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Robert Coleman

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2011
• First Posted: September 27, 2011
• Study Start: September 20, 2011
• Primary Completion: December 31, 2015
• Study Completion: December 31, 2015
• Last Updated: April 5, 2018

Record last verified: 2018-04

Locations

US (1)