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Olaparib or Cediranib Maleate and Olaparib Compared With Standard Platinum-Based Chemotherapy in Treating Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

This study is currently recruiting participants.
Verified November 2017 by National Cancer Institute (NCI)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02446600
First Posted: May 18, 2015
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This randomized phase III trial studies olaparib or cediranib maleate and olaparib to see how well they work compared with standard platinum-based chemotherapy in treating patients with platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer that has come back. Olaparib and cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cediranib maleate may stop the growth of ovarian, fallopian tube, or primary peritoneal cancer by blocking the growth of new blood vessels necessary for tumor growth. Drugs used in chemotherapy, such as carboplatin, paclitaxel, gemcitabine hydrochloride, and pegylated liposomal doxorubicin hydrochloride work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether olaparib or cediranib maleate and olaparib is more effective than standard platinum-based chemotherapy in treating patients with platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.

Condition Intervention Phase
BRCA Rearrangement Deleterious BRCA1 Gene Mutation Deleterious BRCA2 Gene Mutation Fallopian Tube Clear Cell Adenocarcinoma Fallopian Tube Transitional Cell Carcinoma Ovarian Clear Cell Adenocarcinoma Ovarian Endometrioid Tumor Ovarian Seromucinous Carcinoma Ovarian Serous Tumor Ovarian Transitional Cell Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Undifferentiated Fallopian Tube Carcinoma Undifferentiated Ovarian Carcinoma Drug: Carboplatin Drug: Cediranib Maleate Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis Drug: Olaparib Drug: Paclitaxel Drug: Pegylated Liposomal Doxorubicin Hydrochloride Other: Pharmacological Study Other: Quality-of-Life Assessment Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Study Comparing Single-Agent Olaparib or the Combination of Cediranib and Olaparib to Standard Platinum-Based Chemotherapy in Women With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression free survival determined using Response Evaluation Criteria in Solid Tumors version 1.1 criteria [ Time Frame: Date of enrollment (and randomization) onto the study to the date progression as determined by the local clinical staff or death, assessed up to 5 years ]
    The fraction of information will be determined as the observed number of progression free survival events among those who were randomized to the reference regimen at the time of the interim analysis divided by the targeted number of progression free survival events in this group required for the final analysis.


Secondary Outcome Measures:
  • Frequency and severity of adverse effects [ Time Frame: Up to 5 years ]
    Defined by Common Terminology Criteria for Adverse Events version 4.0

  • Overall survival [ Time Frame: Up to 5 years ]
    A logrank test stratified by germline BRCA1/2 mutation status (yes versus no), last platinum-free interval (6-12 months, versus > 12 months) and prior antiangiogenic treatment (yes versus no) will be used to compare the distributions of survival times between treatment groups.

  • Patient reported scores of disease-related symptoms as measured by the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 Disease-Related Symptom-Physical [ Time Frame: Up to 5 years ]
    A mixed-effects model will be used to estimate and compare the mean National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Ovarian Symptom Index-Disease-Related Symptom scores for the treatment groups at each of the follow-up assessment times. Model covariates will include the patients' randomly assigned study treatment, age at enrollment onto the study, initial performance status, pre-treatment National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Ovarian Symptom Index-Disease-Related Symptom score, assessment time and a term for the interaction


Other Outcome Measures:
  • Time from randomization to the first non-study, anti-cancer treatment or death [ Time Frame: Up to 5 years ]
  • Time from randomization to the second non-study, anti-cancer treatment or death [ Time Frame: Up to 5 years ]

Estimated Enrollment: 549
Actual Study Start Date: February 4, 2016
Estimated Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (platinum-based chemotherapy)

REGIMEN I: Patients receive carboplatin IV over 30-60 minutes and paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.

REGIMEN II: Patients receive carboplatin IV over 30-60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 for at least 4 courses in the absence of disease progression or unacceptable toxicity.

REGIMEN III: Patients receive carboplatin IV over 30-60 minutes and pegylated liposomal doxorubicin hydrochloride IV on day 1. Treatment repeats every 28 days for at least 4 courses in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Drug: Pegylated Liposomal Doxorubicin Hydrochloride
Given IV
Other Names:
  • ATI-0918
  • Caelyx
  • DOX-SL
  • Doxil
  • Doxilen
  • Doxorubicin HCl Liposome
  • Doxorubicin Hydrochloride Liposome
  • Duomeisu
  • Evacet
  • LipoDox
  • Liposomal Adriamycin
  • liposomal doxorubicin hydrochloride
  • Liposomal-Encapsulated Doxorubicin
  • Pegylated Doxorubicin HCl Liposome
  • S-Liposomal Doxorubicin
  • Stealth Liposomal Doxorubicin
  • TLC D-99
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Experimental: Arm II (olaparib)
Patients receive olaparib PO BID. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Olaparib
Given PO
Other Names:
  • AZD2281
  • KU-0059436
  • Lynparza
  • PARP Inhibitor AZD2281
Other: Pharmacological Study
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Experimental: Arm III (olaparib, cediranib maleate)
Patients receive olaparib PO BID and cediranib maleate PO QD. 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
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have platinum-sensitive recurrent high-grade serous or high-grade endometrioid ovarian, primary peritoneal, or fallopian tube cancers; patients with other (clear cell, mixed epithelial, undifferentiated carcinoma, or transitional cell carcinoma) high-risk histologies are also eligible, provided that the patient has a known deleterious germline BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory; Note: Due to the long acceptance of germline BRCA testing through Myriad, Myriad testing will be accepted; if testing for germline 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 showed a recognized germline deleterious BRCA1 or BRCA2 mutation or BRCA rearrangement is required; please collect a copy of Myriad or other BRCA mutational analysis (positive or VUS or negative) reports

    • Platinum-sensitive disease defined as no clinical or radiographic evidence of disease recurrence for > 6 months (or 182 days) after last receipt of platinum-based therapy
    • Patients must have had a complete clinical response to their prior line of platinum therapy and cannot have had progression through prior platinum-based therapy
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information
  • Patients must have evaluable disease - defined as one of the following:

    • Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurable disease OR
    • Evaluable disease (defined as solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions OR ascites and/or pleural effusion that has been pathologically demonstrated to be disease-related) AND a cancer antigen 125 (CA125) that has doubled from the post-treatment nadir and is also greater than 2 times upper limit of normal (ULN)
  • Prior therapy:

    • Prior chemotherapy must have included a first-line platinum-based regimen with or without intravenous consolidation chemotherapy
    • Patients may have received an unlimited number of platinum-based therapies in the recurrent setting
    • Patients may have received up to 1 non-platinum-based line of therapy in the recurrent setting; prior hormonal therapy will not be considered to count as this non-platinum-based line
    • Patients may not have had a prior anti-angiogenic agent in the recurrent setting; prior use of bevacizumab in the upfront or upfront maintenance setting is allowed
    • Patients may not have previously received a poly adenosine diphosphate (ADP) ribose polymerase (PARP)-inhibitor
    • Prior hormonal-based therapy for ovarian, primary peritoneal, or fallopian tube cancer is acceptable
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 10 g/dL
  • Creatinine =< the institutional upper limit of normal (ULN) OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Urine protein: creatinine ratio (UPC) of =< 1 or less than or equal to 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart; UPC is the preferred test; patients with >= 2+ proteinuria on dipstick must also have a 24 hour urine collection demonstrating =< 500 mg over 24 hours
  • Total bilirubin =< 1.5 x the institutional ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 times institutional ULN
  • Toxicities of prior therapy (excepting alopecia) should be resolved to less than or equal to grade 1 as per National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0); patients with long-standing stable grade 2 neuropathy may be considered after discussion with the overall principal investigator (PI), but may not receive carboplatin and paclitaxel as the reference regimen, if randomized to that arm
  • Patients must be able to swallow and retain oral medications and without gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
  • Patients must have adequately controlled blood pressure (BP), with a BP no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility; patients must have a BP of =< 140/90 mmHg taken in the clinic setting by a medical professional within 2 weeks prior to starting study; patients with hypertension may be managed with up to a maximum of three antihypertensive medications; it is strongly recommended that patients who are on three antihypertensive medications be followed by a cardiologist or blood pressure specialist for management of blood pressure while on protocol
  • Patients must be willing and able to check and record daily blood pressure readings; blood pressure cuffs will be provided to patients randomized to Arm III
  • Women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential must agree to use two reliable forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 weeks after cediranib discontinuation; should a woman become pregnant or suspect she is pregnant while 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

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of starting treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients may not have had hormonal therapy within 2 weeks prior to entering the study; patients receiving raloxifene for bone health as per Food and Drug Administration (FDA) indication may remain on raloxifene absent other drug interactions
  • Patients may not be receiving any other investigational agents nor have participated in an investigational trial within the past 4 weeks
  • Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)
  • Patients may not have received prior treatment affecting the vascular endothelial growth factor (VEGF) pathway (including, but not limited to thalidomide, sunitinib, pazopanib, sorafenib, and nintedanib); bevacizumab used in the upfront setting in conjunction with chemotherapy and/or as maintenance to treat newly diagnosed disease will be allowed
  • Patients may not have previously received a PARP inhibitor
  • CA-125 only disease without RECIST 1.1 measurable or otherwise evaluable disease
  • 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 should not be included on this study; 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 and resolution of any associated symptoms must demonstrate stable post-therapeutic imaging for at least 6 months following therapy prior to starting study drug
  • 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) are ineligible; strong inhibitors and inducers of UGT/PgP should be used with caution
  • History of gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired or has healed, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula
  • History of intra-abdominal abscess within the past 3 months
  • Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months prior to starting study drugs
  • Dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)
  • Any concomitant or prior invasive malignancies with the following curatively treated 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/serous, clear cell, or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
    • Prior cancer treated with a curative intent with no evidence of recurrent disease 3 years following diagnosis and judged by the investigator to be at low risk of recurrence
  • Patients with any of the following:

    • History of myocardial infarction within six months
    • Unstable angina
    • Resting electrocardiogram (ECG) with clinically significant abnormal findings
    • New York Heart Association (NYHA) classification of III or IV
  • If cardiac function assessment is clinically indicated or performed: left ventricular ejection fraction (LVEF) less than normal per institutional guidelines, or < 55%, if threshold for normal not otherwise specified by institutional guidelines

    • Patients with 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)
      • Prior history of impaired cardiac function
  • History of stroke or transient ischemic attack within six months
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
  • Clinically significant peripheral vascular disease or vascular disease (including aortic aneurysm or aortic dissection)
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (other than atrial fibrillation with controlled ventricular rate), or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with cediranib or olaparib
  • Known human immunodeficiency virus (HIV)-positive individuals are ineligible
  • Patients may not use any complementary or alternative medicines including natural herbal products or folk remedies
  • No features suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated
  • No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUBCT)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02446600


  Show 358 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
AstraZeneca
Investigators
Principal Investigator: Joyce Liu NRG Oncology
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02446600     History of Changes
Other Study ID Numbers: NCI-2015-00606
NCI-2015-00606 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NRG-GY004
s16-01480
NRG-GY004 ( Other Identifier: NRG Oncology )
NRG-GY004 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
First Submitted: May 11, 2015
First Posted: May 18, 2015
Last Update Posted: November 17, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Carcinoma
Adenocarcinoma
Carcinoma, Transitional Cell
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Fallopian Tube Neoplasms
Adenocarcinoma, Clear Cell
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Paclitaxel
Gemcitabine
Liposomal doxorubicin
Olaparib
Cediranib
Carboplatin
Doxorubicin
Maleic acid
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators