Clinical Trials /

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

NCT02059265

Description:

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

Related Conditions:
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dasatinib in Treating Patients With Recurrent or Persistent Ovarian, Fallopian Tube, Endometrial or Peritoneal Cancer
  • Official Title: A Phase II Trial of DCTD-Sponsored Dasatinib in Recurrent/Persistent Ovary, Fallopian Tube, Primary Peritoneal, and Endometrial Clear Cell Carcinoma Characterized for the Retention or Loss of BAF250a Expression

Clinical Trial IDs

  • ORG STUDY ID: NCI-2014-00209
  • SECONDARY ID: NCI-2014-00209
  • SECONDARY ID: GOG-0283
  • SECONDARY ID: GOG-0283
  • SECONDARY ID: GOG-0283
  • SECONDARY ID: U10CA180868
  • SECONDARY ID: U10CA027469
  • NCT ID: NCT02059265

Conditions

  • Endometrial Clear Cell Adenocarcinoma
  • Estrogen Receptor Negative
  • Ovarian Clear Cell Cystadenocarcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Recurrent Uterine Corpus Carcinoma

Interventions

DrugSynonymsArms
DasatinibBMS-354825, SprycelTreatment (dasatinib)

Purpose

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

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 BRG-associated
      factor 250a (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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (dasatinib)ExperimentalPatients receive dasatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Dasatinib

Eligibility 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 (with the exception of
             endometrial cancers where WT-1 stains are not required) and estrogen receptor (ER)
             antigen by immunohistochemistry; focal, weak, ER staining of tumor cells (< 5%) is
             permitted; 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

          -  Patients must have results from the determination of BAF250a immunohistochemistry
             (IHC) status and must have a BAF250a expression status that is currently open to
             enrollment

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:OS will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.
Measure: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
Safety Issue:
Description:PFS will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.
Measure:Incidence of adverse effects as assessed by Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 5 years
Safety Issue:
Description:The frequency and severity of all toxicities are tabulated.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:National Cancer Institute (NCI)

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