Trial record 12 of 26 for:    parp inhibitor ovarian | Open Studies

Olaparib and Cediranib Maleate in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02345265
First received: January 23, 2015
Last updated: January 18, 2017
Last verified: January 2017
  Purpose
This phase II trial studies how well olaparib and cediranib maleate work in treating patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back (recurrent). Olaparib and cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition Intervention Phase
BRCA1 Gene Mutation
BRCA2 Gene Mutation
Fallopian Tube Endometrioid Adenocarcinoma
Fallopian Tube Serous Adenocarcinoma
High Grade Ovarian Serous Adenocarcinoma
Ovarian Endometrioid Tumor
Primary Peritoneal Serous Adenocarcinoma
Recurrent Fallopian Tube Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Primary Peritoneal Carcinoma
Drug: Cediranib Maleate
Other: Laboratory Biomarker Analysis
Drug: Olaparib
Other: Pharmacological Study
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Olaparib and Cediranib for the Treatment of Recurrent Ovarian Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Biomarker signature development [ Time Frame: Up to 30 days post-treatment ]
    Will summarize the distribution of all candidate markers using descriptive statistics and non-parametric tests of their association with patient and disease characteristics. Biomarker profiles will be explored using unsupervised hierarchical clustering of all analytes and patients. The association of each candidate marker to PFS will be evaluated by Cox proportional hazard models using a two-sided alpha = 0.05, while estimating the false discovery rate for any sets of identified markers by the Benjamini-Hochberg step-up procedure.

  • Objective response rate, defined as confirmed complete response or partial response under RECIST 1.1 (Platinum-Resistant Cohort) [ Time Frame: Up to 1 year ]
  • Progression-free survival (PFS) [ Time Frame: Interval from start of treatment to documented disease progression per RECIST or death from any cause, whichever occurs first, assessed up to 1 year ]

Secondary Outcome Measures:
  • Change in circulating endothelial cells (CEC)/ circulating endothelial precursor cells (CEP) [ Time Frame: Baseline to day 3 ]
    Will determine if there is an association between levels of CEC at baseline, or the change in CEC from baseline to day 3, and PFS in patients receiving cediranib maleate/olaparib trial, and to determine if there are significant changes from baseline to day 3 in the levels of CEC. Will use a paired t-test. In addition, if the paired differences in values are not normally distributed (p < 0.05 by a Shapiro-Wilk test), then a Wilcoxon signed rank test will be used instead of a paired t-test.

  • Genetic alterations detected by the BROCA-homologous recombination (HR) assay [ Time Frame: Baseline ]
    Descriptive statistics will be used to summarize the genetic alterations detected by the BROCA-HR assay and Bioinformatics Pipeline. The prevalence of each genetic alteration will be reported overall, and within stratum defined by platinum-sensitive and platinum-resistant disease using binomial exact 95% confidence intervals. The primary analysis will associate BRCA mutations (germline or somatic) and other HR gene mutation (as a pooled group) with/against PFS as a time-to-event endpoint, using Kaplan-Meier product-limit estimates and stratified logrank test using a two-sided alpha of 0.05.

  • Overall survival [ Time Frame: Up to 1 year ]
  • Prevalence of genetic alteration using whole exome sequencing [ Time Frame: Baseline ]
    The prevalence of each genetic alteration will be reported overall, and within platinum-sensitive and platinum-resistant cohorts using binomial exact 95% confidence intervals. Exploratory analyses will associate alterations of a single-gene against progression-free survival as a time-to-event endpoint, using Kaplan-Meier product-limit estimates and logrank test using a nominal two-sided alpha of 0.05.

  • Vascular endothelial growth factor receptor 3 (VEGFR3) expression and quantification [ Time Frame: Baseline ]
    VEGFR3 expression will be assessed by immunohistochemistry (IHC) and quantified as percent cell staining. The association of VEGFR3 expression to PFS will be summarized using the Kaplan-Meier estimator and confidence bands defined by Greenwood's formula. Univariate and multivariate Cox proportional hazards models will be used to estimate hazard ratios (and 95% confidence intervals), and conduct Wald-type tests of association. Association of VEGFR3 to PFS in BRCA wild-type patients is a subgroup analysis. Association to objective response will use univariate and multivariate regression models.


Other Outcome Measures:
  • eCO app web portal metrics [ Time Frame: Up to 1 year ]
    Web portal metrics will be summarized using descriptive statistics. The metrics will include:number of patients who accessed the app, number of diarrhea events reported, % blood pressure (BP) values entered compared to the % expected, number of follow-up BP measures entered compared to the number recommended, number and type of BP events reported, average duration of BP event and diarrhea event in days, number of other symptoms reported (headache, change in vision, shortness of breath, chest pain, uncontrolled diarrhea, cramping, blood in stool), number and type of email alerts generated to th

  • Incidence of eCO app user support call [ Time Frame: Up to 1 year ]
    User support calls will be summarized including: number of calls and the reason for contacting eCO user support (patients and study team).

  • Perceived usability and satisfaction of eCO app from health care professionals [ Time Frame: Up to 1 year ]
    Significance testing of data from patients and healthcare professionals will be done using a one tailed Wilcoxon signed rank test (alpha = 0.05).

  • Perceived usability and satisfaction of eCO app from patients [ Time Frame: Up to 1 year ]
    Significance testing of data from patients and healthcare professionals will be done using a one tailed Wilcoxon signed rank test (alpha = 0.05).


Estimated Enrollment: 70
Study Start Date: December 2015
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (olaparib and cediranib maleate)
Patients receive olaparib PO BID and cediranib maleate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Cediranib Maleate
Given PO
Other Names:
  • AZD2171
  • AZD2171 Maleate
  • Recentin
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Olaparib
Given PO
Other Names:
  • AZD2281
  • KU-0059436
  • Lynparza
  • PARP Inhibitor AZD2281
Other: Pharmacological Study
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of either high grade serous or high grade endometrioid cancer based on local histopathological findings; participants with a deleterious BRCA-mutation on a commercial Clinical Laboratory Improvement Amendments (CLIA) assay with other high-grade histologies are also eligible

    • Due to the long acceptance of BRCA testing through Myriad, Myriad testing will be accepted as documentation of a deleterious mutation; if testing for BRCA is done by other organizations, documentation from a qualified medical professional (e.g., ovarian cancer specialty physician involved in the field, high risk genetics physician, genetics counselor) listing the mutation and confirming that the laboratory results show a recognized germline deleterious BRCA1 or BRCA2 mutation or BRCA rearrangements is required to document the presence of a deleterious mutation
  • Participants must have measurable disease via Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Patients may not have received prior poly ADP ribose polymerase (PARP) inhibitors
  • Patients may have received but may not have progressed on prior anti-angiogenic therapy in the upfront setting
  • For platinum sensitive cohort

    • Cancer that has not progressed within 6 months of the last receipt of platinum-based chemotherapy
    • No limit on the number of platinum-based lines
    • No more than one prior non-platinum based line of therapy in the recurrent setting
  • For platinum-resistant or -refractory cohort

    • Disease that has progressed within 6 months of the last receipt of platinum-based chemotherapy
    • No more than 1 prior line of therapy in the platinum-resistant/-refractory setting
    • No limit on number of prior lines received in the platinum-sensitive setting prior to development of platinum-resistance (defined as disease progression within 6 months of platinum-based chemotherapy)
  • Hormonal therapies used as single agents (i.e. tamoxifen, aromatase inhibitors) will not count towards line limit considerations
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Hemoglobin >= 10 g/dL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
  • Creatinine less than or equal to the institutional upper limit of normal or creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
  • Proteinuria less than or equal to 1+ proteinuria on two consecutive dipsticks taken no less than week apart, or a urine protein:creatinine (UPC) ration of =< 1
  • Coagulation parameters (international normalized ratio [INR], activated partial thromboplastin time [aPTT]) =< 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed
  • Presence of biopsiable disease and willingness to undergo pre-treatment biopsy
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and up to 3 months after end of treatment; 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
  • Adequately controlled thyroid function, with no symptoms of thyroid dysfunction and thyroid stimulating hormone (TSH) within normal limits
  • Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
  • Ability to understand and the willingness to sign a written informed consent document
  • Willingness to release and confirmed availability of archival tissue sample for research purposes
  • Willingness and ability to check and record daily blood pressure readings; blood pressure cuffs will be provided to patients

Exclusion Criteria:

  • Participants may not have had chemotherapy or radiation therapy (RT) within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered from adverse events due to agents administered more than 3 weeks earlier; patients should not have received hormonal therapy for treatment of their cancer within 2 weeks of study entry
  • Participants should not have received any other investigational agents nor have participated in an investigational trial within the past 4 weeks
  • Participants may not have had prior use of poly ADP ribose polymerase (PARP) inhibitors; patients may not have received prior treatment affecting the vascular endothelial growth factor (VEGF) pathway in the recurrent setting, including but not limited to thalidomide, bevacizumab, sunitinib, or sorafenib
  • Participants may not have any evidence of ongoing inadequately controlled hypertension (defined as a systolic blood pressure [BP] of > 140 mmHg or a diastolic BP of > 90 mmHg); patients with hypertension may not be on more than three antihypertensive medications for management of their blood pressure (medications that combine two anti-hypertensives into one are considered as two medications); it is strongly recommended that patients who require three antihypertensive medications for baseline management of pre-existing hypertension be actively followed by a cardiologist or blood pressure specialist for management of BP while on protocol
  • Participants may not have had any prior history of hypertensive crisis or hypertensive encephalopathy
  • Participants may not have had history of abdominal fistula or gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula has healed or was surgically repaired, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula
  • Participants may not have had a history of intra-abdominal abscess within the past 3 months
  • Participants may not have current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months prior to starting study drugs
  • Participants may not have a dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)
  • Participants with any concomitant or prior invasive malignancies are ineligible with the following exceptions:

    • Treated limited-stage basal cell or squamous cell carcinoma of the skin
    • Carcinoma in situ of the breast or cervix
    • Primary endometrial cancer meeting the following conditions: stage not greater than IA, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell, or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
    • Prior cancer treated with curative intent with no evidence of recurrent disease 3 years following diagnosis and judged by the investigator to be at low risk of recurrence
  • Participants with any of the following:

    • History of myocardial infarction within six months
    • Unstable angina
    • New York Heart Association (NYHA) classification of III or IV
  • If cardiac function assessment is clinically indicated or performed: participants will be ineligible if left ventricular ejection fraction (LVEF) is less than normal per institutional guidelines, or < 55%, if the threshold for normal is not otherwise specified by institutional guidelines
  • Patients with any of the following risk factors should have a baseline cardiac function assessment:

    • Prior treatment with anthracyclines
    • Prior treatment with trastuzumab
    • Prior central thoracic radiation therapy (RT), including RT to the heart
    • History of myocardial infarction within 6 to 12 months (patients with history of myocardial infarction within 6 months are excluded from the study
    • A NYHA classification of II controlled with treatment
    • Prior history of impaired cardiac function
  • Participants may not have had a history of a stroke or transient ischemic attack within six months
  • Participants should not have clinically significant peripheral vascular disease or vascular disease (including aortic aneurysm or aortic dissection)
  • Participants may not have a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib
  • Participants should not have any uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans are ineligible; screening imaging to rule out brain metastases is not required for screening, but should be performed prior to study enrollment if clinically indicated; patients with treated brain metastases must demonstrate stable post-therapeutic imaging and resolution of any associated symptoms and must be stably off steroids with no symptoms for at least 6 months following therapy prior to starting study drug
  • Participants may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib or olaparib
  • Participants receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or moderate inhibitors of CYP3A4 are ineligible; dihydropyridine calcium-channel blockers are permitted for management of hypertension
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with cediranib and olaparib
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Participants should not have evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted
  • Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:

    • Other anti-cancer therapy while on study treatment
    • Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
    • The concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, cannabis, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng)
    • Raloxifene is allowed for patients taking it for bone health
  • Participants may not have any features suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated
  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: NCT02345265

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Andrea E. Wahner Hendrickson    855-776-0015      
Principal Investigator: Andrea E. Wahner Hendrickson         
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Mihaela C. Cristea    800-826-4673    becomingapatient@coh.org   
Principal Investigator: Mihaela C. Cristea         
Los Angeles County-USC Medical Center Recruiting
Los Angeles, California, United States, 90033
Contact: Koji Matsuo    323-865-0451      
Principal Investigator: Koji Matsuo         
USC / Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Koji Matsuo    323-865-0451      
Principal Investigator: Koji Matsuo         
Keck Medical Center of USC Pasadena Recruiting
Pasadena, California, United States, 91105
Contact: Koji Matsuo    323-865-0451      
Principal Investigator: Koji Matsuo         
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Andrea E. Wahner Hendrickson    855-776-0015      
Principal Investigator: Andrea E. Wahner Hendrickson         
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Robert M. Wenham    800-456-7121    canceranswers@moffitt.org   
Principal Investigator: Robert M. Wenham         
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Deborah K. Armstrong    410-955-8804    jhcccro@jhmi.edu   
Principal Investigator: Deborah K. Armstrong         
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Jung-min Lee    800-411-1222      
Principal Investigator: Jung-min Lee         
NCI - Center for Cancer Research Recruiting
Bethesda, Maryland, United States, 20892
Contact: Jung-min Lee    800-411-1222      
Principal Investigator: Jung-min Lee         
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Joyce F. Liu    877-442-3324      
Principal Investigator: Joyce F. Liu         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Joyce F. Liu    877-442-3324      
Principal Investigator: Joyce F. Liu         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Joyce F. Liu    877-442-3324      
Principal Investigator: Joyce F. Liu         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Andrea E. Wahner Hendrickson    855-776-0015      
Principal Investigator: Andrea E. Wahner Hendrickson         
United States, New Jersey
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Nancy Chan    732-235-8675      
Principal Investigator: Nancy Chan         
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Nancy Chan    732-235-8675      
Principal Investigator: Nancy Chan         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Herbert I. Hurwitz    888-275-3853      
Principal Investigator: Herbert I. Hurwitz         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: David M. O'Malley    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: David M. O'Malley         
United States, Pennsylvania
University of Pittsburgh Cancer Institute (UPCI) Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Alexander B. Olawaiye    412-647-2811      
Principal Investigator: Alexander B. Olawaiye         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Joyce Liu Dana-Farber - Harvard Cancer Center LAO
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02345265     History of Changes
Other Study ID Numbers: NCI-2015-00051  NCI-2015-00051  16-700  9825  9825  P30CA006516  UM1CA186644  UM1CA186686  UM1CA186690  UM1CA186691  UM1CA186704  UM1CA186709  UM1CA186712  UM1CA186716  UM1CA186717  ZIABC011078 
Study First Received: January 23, 2015
Last Updated: January 18, 2017

Additional relevant MeSH terms:
Ovarian Neoplasms
Ovarian Diseases
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Protein Kinase Inhibitors
Adenocarcinoma
Carcinoma
Carcinoma, Endometrioid
Cystadenocarcinoma, Serous
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Endometrial Neoplasms
Uterine Neoplasms
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Fallopian Tube Diseases
Olaparib
Cediranib
Maleic acid
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on January 19, 2017