Dasatinib in Treating Patients With Recurrent or Persistent Ovarian, Fallopian Tube, Endometrial or Peritoneal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02059265
First received: February 7, 2014
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

This phase II trial studies how well dasatinib works in treating patients with persistent ovarian, fallopian tube, endometrial, or peritoneal cancer. Dasatinib may shrink patients' tumors by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Endometrial Clear Cell Carcinoma
Ovarian Clear Cell Cystadenocarcinoma
Recurrent Endometrial Carcinoma
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Drug: dasatinib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of DCTD-Sponsored Dasatinib (NSC #732517) in Recurrent/Persistent Ovary, Fallopian Tube, Primary Peritoneal, and Endometrial Clear Cell Carcinoma Characterized for the Retention or Loss of BAF250a Expression

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients with objective tumor response rate (complete response [CR] or partial response [PR]) using RECIST version 1.1 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of progression-free survival (PFS) [ Time Frame: Duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]
    PFS will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.

  • Duration of overall survival (OS) [ Time Frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years ] [ Designated as safety issue: No ]
    OS will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.

  • Frequency and severity of adverse effects as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    The frequency and severity of all toxicities are tabulated.


Other Outcome Measures:
  • ARID1A mutation status in FFPE using next-generation exon-capture sequencing [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    ARID1A mutation status will be tabulated to determine the correlation between BAF250a immunohistochemistry (IHC) and ARID1A mutations.


Estimated Enrollment: 62
Study Start Date: February 2014
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (dasatinib)
Patients receive dasatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the clinical activity of dasatinib in patients with recurrent or persistent ovarian, fallopian tube, primary peritoneal, and endometrial clear cell carcinoma using objective tumor response (complete and partial): in patients without loss of BAF250a expression and in patients with loss of BAF250a expression.

SECONDARY OBJECTIVES:

I. To examine the nature and degree of toxicity in this patient population treated with this regimen in patients with and without loss of BAF250a expression.

II. To examine the progression-free survival and overall survival for this patient population receiving dasatinib in patients with and without loss of BAF250a expression.

TERTIARY OBJECTIVES:

I. To examine the agreement between BAF250a immunohistochemistry and AT rich interactive domain 1A (SWI-like) (ARID1A) mutation status using next generation sequencing performed in formalin-fixed, paraffin-embedded tumor tissue.

OUTLINE:

Patients receive dasatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have recurrent or persistent ovarian, fallopian tube, peritoneum, and endometrial clear cell carcinoma; primary tumors must be at least 50% clear cell histomorphology in order to be eligible or have a histologically documented recurrence with at least 50% clear cell histomorphology; in addition, the tumors should be negative for expression of Wilms tumor 1 (WT-1) antigen and estrogen receptor (ER) antigen by immunohistochemistry; appropriate tissue sections must be available for histologic evaluation for central pathology review by Gynecologic Oncology Group (GOG); immunohistochemical stained slides for ER and WT-1 antigen must be available for review by GOG

    • If the primary tumor had at least 50% clear cell histomorphology, a biopsy of the recurrent or persistent tumor is not required; however, immunohistochemical studies of the primary tumor for ER and WT-1 antigens should be performed and the slides submitted to the GOG for review; the percentage of clear cell histomorphology must be documented in the pathology report or in an addendum to the original report; if slides of the primary tumor are not available for review due to disposal of slides by the histology laboratory (typically 10 years after diagnosis), biopsy of recurrent or persistent disease is required
    • If the primary tumor had less than 50% clear cell histomorphology (or if slides of the primary tumor are not available for review), a biopsy of the recurrent or persistent tumor is required to confirm at least 50% clear cell histomorphology and lack of immuno-reactivity for ER and WT-1 antigens by immunohistochemistry; the percentage of involvement must be documented in the pathology report or in an addendum to the original report
  • Five unstained formalin-fixed, paraffin-embedded (FFPE) tumor tissue slides (charged, 5 um) must be submitted to the central study laboratory (i.e., Clinical Laboratory Improvement Amendments [CLIA]-certified immuno-pathology laboratory at Memorial Sloan-Kettering Cancer Center) for determination of BAF250a immunohistochemistry (IHC) status
  • All patients must have measurable disease; measurable disease is defined by Response Evaluation Criteria In Solid Tumors (RECIST) (version 1.1); measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography [CT], magnetic resonance imaging [MRI] or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be > 15 mm in short axis when measured by CT or MRI
  • Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease; patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease
  • Patients must be >= 3 weeks from last chemotherapy or radiation (6 weeks for nitrosoureas or mitomycin)
  • Patients must have progressed on, be ineligible for, or have declined participation in GOG-0254 provided that protocol is actively accruing patients
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Creatinine =< 1.5 times the upper limit of normal (ULN) OR
  • Creatinine clearance >= 60 mL/min/1.73 m^2
  • Bilirubin =< 1.5 ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase ALT (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN
  • Patients who are on concomitant medications that are STRONG inducers or inhibitors of the cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) enzyme should stop 2 weeks prior to first dose of dasatinib, if all other eligibility has been confirmed
  • Corrected QT (QTc) interval on electrocardiogram must be =< 480 msec (Fridericia correction)
  • Patients who have received one prior regimen must have a GOG performance status of 0, 1 or 2; patients who have received two or more prior regimens must have GOG performance status of 0 or 1
  • Patients who have met the pre-entry requirements
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

  • Prior treatment with dasatinib, imatinib or nilotinib
  • As dasatinib can cause fluid shifts, patients with symptomatic effusions (pleural, pericardial, or peritoneal) and/or those who have required a procedure for symptomatic effusions within 4 weeks of start of dasatinib are ineligible
  • Patients with a history of cardiac disease including: (1) uncontrolled angina, congestive heart failure, or myocardial infarction within six months prior to study entry, (2) congenital long QT syndrome, (3) clinical significant ventricular arrhythmias
  • The concomitant use of histamine (H) 2 blockers and proton pump inhibitors (PPIs) with dasatinib is not recommended; the use of antacids should be considered in place of H2 blockers or proton pump inhibitors 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 who cannot tolerate discontinuation of H2 blockers or PPIs are ineligible
  • 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
  • Patients whose circumstances do not permit completion of the study or the required follow-up
  • Patients who are pregnant or nursing; women of child-bearing potential 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 and for 3 months after completion of therapy; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; a negative serum pregnancy test within 72 hours of starting drug is required
  • Patients who have a major surgical procedure, or significant traumatic injury within 28 days prior to the first date of treatment on this study, or anticipation of need for major surgical procedure during the course of the study; patients with placement of vascular access device or core biopsy within 7 days prior to the first date of treatment on this study
  • Patients with other invasive malignancies, with the exception of non melanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients who are unable to swallow pills
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02059265

  Show 80 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: David Hyman Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02059265     History of Changes
Other Study ID Numbers: NCI-2014-00209, NCI-2014-00209, GOG-0283, GOG-0283, U10CA027469
Study First Received: February 7, 2014
Last Updated: August 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Cystadenocarcinoma
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Adenocarcinoma, Clear Cell
Adenomyoepithelioma
Endometrial Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Abdominal Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Fallopian Tube Diseases
Adnexal Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Uterine Neoplasms
Uterine Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on August 26, 2014