A Phase II Evaluation of Dasatinib (Sprycel®, NSC #732517) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

Recurrent Ovarian Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00671788
• Other study ID #: GOG-0170M
• Secondary ID: NCI-2011-03824CD
• Status: Completed
• Phase: Phase 2
• First received: May 2, 2008
• Last updated: December 29, 2014
• Start date: June 2008

Study information

• Verified date: December 2014
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Fallopian Tube Neoplasms
• Ovarian Neoplasms
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma

Intervention

Drug:
• Dasatinib
Given orally

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Upstate Carolina CCOP	Spartanburg	South Carolina
United States	Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield	Springfield	Missouri
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Tulsa Cancer Institute	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival at 6 Months	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.; CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response.	Scans to assess progression were done every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.	No
Primary	Tumor Response	Complete and Partial Tumor Response by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Per RECIST v1.0 for target lesions and assessed by MRIor CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD.; CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response.	Every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.	No
Secondary	Frequency and Severity of Adverse Events as Assessed by CTCAE v3.0		Every cycle during treatment	Yes
Secondary	Progression-free Survival	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.; CT scan or MRI is used to follow lesion for measurable disease every other cycle for the first 6 months; every three months thereafter; and at any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tumor marker levels. Responses must be confirmed by repeat imaging 4 weeks following documentation of response.	Every other cycle for the first 6 months; every three months thereafter; and any time if clinically indicated based on symptoms or physical signs suggestive of progressive disease.	No
Secondary	Overall Survival		Every other cycle up to 5 years	No