Brief Title
A Phase II Evaluation of Dasatinib (Sprycel®, NSC #732517) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
Official Title
A Phase II Evaluation of Dasatinib (Sprycel®, NSC #732517) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
Brief Summary
Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
growth. This phase II trial is studying how well dasatinib works in treating patients with
persistent or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary
peritoneal cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To estimate the proportion of patients who survive progression-free for at least 6 months
and the proportion of patients who have objective tumor response (complete or partial) in
patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary
peritoneal carcinoma.
SECONDARY OBJECTIVES:
I. To determine the frequency and severity of adverse events as assessed by CTCAE v3.0.
II. To determine the duration of progression-free survival and overall survival.
TERTIARY OBJECTIVES:
I. Objectives in formalin-fixed and paraffin-embedded (FFPE) tumor tissue before treatment
with dasatinib.
II. Explore the association between the expression and phosphorylation of biomarkers involved
in Src signaling pathways and measures of clinical outcome as well as disease status.
III. Bank residual FFPE tumor tissue for the development and characterization of predictive
and/or prognostic biomarkers or the validation of thereapeutic targets.
IV. Objectives in blood drawn before and/or during treatment with dasatinib. V. Isolate,
enumerate and characterize circulating tumor cells (CTC) as well as circulating endothelial
cells (CEC)/circulating endothelial precursors (CEP).
VI. Prepare a buffy-coat specimen from residual blood remaining after isolation of CTC and
CEC/CEP.
VII. Explore whether CTC and CEC/CEP counts or characteristics are associated with measures
of clinical outcome and disease status.
VIII. Explore whether the expression and phosphorylation of biomarkers involved in Src
signaling pathways in CTC and CEC/CEP are associated with measures of clinical outcome and
disease status.
IX. Explore the associations between germline single nucleotide polymorphisms (SNPs) in genes
involved in drug metabolism, resistance and DNA repair and measures of clinical outcome and
disease status.
X. Bank residual DNA and buffy-coat specimens for the development and characterization of
predictive and/or prognostic biomarkers or the validation of therapeutic targets.
XI. Objectives in plasma prepared from blood drawn before and/or during treatment with
dasatinib.
XII. Explore the association between angiogenic markers and cytokines including VEGF and
measures of clinical outcome and disease status.
XIII. Explore the association between measures of cell-free DNA and measures of clinical
outcome and disease status.
XIV. Bank residual plasma for the development and characterization of predictive and/or
prognostic biomarkers or the validation of therapeutic targets.
OUTLINE: This is a multicenter study.
Patients receive oral dasatinib once daily 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 every 3 months for 2 years and
then every 6 months for 3 years.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression-free Survival at 6 Months
Secondary Outcome
Frequency and Severity of Adverse Events as Assessed by CTCAE v3.0
Condition
Recurrent Fallopian Tube Carcinoma
Intervention
Dasatinib
Study Arms / Comparison Groups
Treatment (dasatinib)
Description: Patients receive oral dasatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
35
Start Date
June 2008
Primary Completion Date
December 2010
Eligibility Criteria
Inclusion Criteria:
- Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or
primary peritoneal carcinoma; histologic documentation of the original primary tumor
is required via the pathology report
- 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, CT, and MRI, or >= 10 mm when measured
by spiral CT
- 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 not be eligible for a higher priority GOG protocol, if one exists; in
general, this would refer to any active GOG Phase III protocol for the same patient
population
- Patients who have received one prior regimen must have a GOG Performance Status of 0,
1, or 2; patients who have received two prior regimens must have a GOG Performance
Status of 0 or 1
- Recovery from effects of recent surgery, radiotherapy, or chemotherapy
- Patients should be free of active infection requiring antibiotics (with the
exception of uncomplicated UTI).
- Any hormonal therapy directed at the malignant tumor must be discontinued at
least one week prior to registration; continuation of hormone replacement therapy
is permitted
- Any other prior therapy directed at the malignant tumor, including immunologic
agents, must be discontinued at least three weeks prior to registration; six
weeks for patient previously treated with monoclonal antibodies
- Prior therapy
- Patients must have had one prior platinum-based chemotherapeutic regimen for
management of primary disease containing carboplatin, cisplatin, or another
organoplatinum compound; this initial treatment may have included intraperitoneal
therapy, high-dose therapy, consolidation, non-cytotoxic agents or extended
therapy administered after surgical or non-surgical assessment
- Patients are allowed to receive, but are not required to receive, one additional
cytotoxic regimen for management of recurrent or persistent disease according to
the following definition:
- Cytotoxic regimens include any agent that targets the genetic and/or mitotic
apparatus of dividing cells, resulting in dose-limiting toxicity to the bone
marrow and/or gastrointestinal mucosa
- Note: patients on this non-cytotoxic study are allowed to receive additional
cytotoxic chemotherapy for management of recurrent or persistent disease, as
defined above
- Patients must have NOT received any non-cytotoxic therapy for management of
recurrent or persistent disease; patients are allowed to receive, but are not
required to receive, biologic (non-cytotoxic) therapy as part of their primary
treatment regimen
- Patients who have received only one prior cytotoxic regimen (platinum-based
regimen for management of primary disease), must have a platinum-free interval of
less than 12 months, or have progressed during platinum-based therapy, or have
persistent disease after a platinum-based therapy
- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to
CTCAE v 3.0 grade 1
- Platelets greater than or equal to 100,000/mcl
- Hemoglobin greater than or equal to 10 g/dL
- Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE
v3.0 grade 1
- Bilirubin less than or equal to 1.5 x ULN, CTCAE v3.0 grade 1
- SGOT and alkaline phosphatase less than or equal to 2.5 x ULN, CTCAE v3.0 grade 1
- Mg++, CA++, phosphate, K+, Na corrected to WNL
- PT/INR, PTT less than or equal to 1 - 1.5 x ULN, CTCAE v 3.0 grade 1 except for
patients on therapeutic anticoagulation
- Neuropathy (sensory and motor) less than or equal to CTCAE v 3.0 grade 1
- QTc interval on electrocardiogram must be less than or equal to 450 msec
- Patients must have signed an approved informed consent and authorization permitting
release of personal health information
- Patients must meet pre-entry requirements as specified in section 7.0
- Patients of childbearing potential must have a negative serum pregnancy test within 72
hours prior to initiating protocol therapy and be practicing an effective form of
contraception during protocol therapy and for at least 4 weeks following completion of
protocol therapy
- Patients must not be receiving any other investigational agent
- Patients must be able to swallow whole pills
Exclusion Criteria:
- Patients who have had previous treatment with dasatinib
- Patients who have received radiation to more than 25% of marrow-bearing areas
- Patients with a history of other invasive malignancies, with the exception of
non-melanoma skin cancer and other specific malignancies are excluded if there is any
evidence of other malignancy being present within the last five years; patients are
also excluded if their previous cancer treatment contraindicates this protocol therapy
- Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or primary
peritoneal cancer within the last five years are excluded; prior radiation for
localized cancer of the breast, head and neck, or skin is permitted, provided that it
was completed more than three years prior to registration, and the patient remains
free of recurrent or metastatic disease
- Patients cannot take St. John's Wort or drink grapefruit juice while on study
treatment (discontinue St. John's Wort at least five days before starting dasatinib)
- 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 who have a history of cardiac disease:
- Uncontrolled angina, congestive heart failure (CHF) or myocardial infarction (MI)
within six months prior to study entry;
- Diagnosed congenital long QT syndrome;
- Clinically significant ventricular arrhythmias (such as ventricular tachycardia
[VT], ventricular fibrillation [VF], or Torsades de pointes)
- Patients with hypokalemia or hypomagnesemia if it cannot be corrected to within normal
limits prior to dasatinib treatment
- 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 GI bleeding within three months prior to initiating protocol therapy
- Dasatinib is metabolized primarily by the CYP3A4 liver enzyme; consideration should be
given to using alternative medications not impacting CYP3A4 while on dasatinib therapy
- Patients may not be receiving any prohibited potent CYP3A4 inhibitors; for these
drugs, a wash-out period of >= 7 days is required prior to starting dasatinib
treatment
- Category I drugs that are generally accepted to have a risk of causing Torsades de
Pointes; a wash-out period of >= 7 days is required for the following drugs prior to
starting dasatinib treatment:
- Quinidine, procainamide, disopyramide
- Amiodarone, sotalol, ibutilide, dofetilide
- Erythromycin, clarithromycin
- Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
- Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
- The concomitant use of H2 blockers and proton pump inhibitors (PPIs) with dasatinib is
not recommended (e.g., famotidine, omeprazole); 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
- 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 PT/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
- Pregnant or nursing women; women of childbearing potential unless using effective
contraception as determined by the investigator
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Russell Schilder, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00671788
Organization ID
GOG-0170M
Secondary IDs
NCI-2011-03824
Responsible Party
Sponsor
Study Sponsor
Gynecologic Oncology Group
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Russell Schilder, Principal Investigator, Gynecologic Oncology Group
Verification Date
March 2016