Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer

NCT01116648 | Active Not Recruiting Phase 1 Results FDA Drug

• 9 other identifiers: NCI-2012-02938NCI-2010-01329DFCI IRB 09-293NCI-2013-005788348N01CM00071P30CA006516U01CA062490UM1CA186709
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 14

Brief Summary

This partially randomized phase I/II trial studies the side effects and the best dose of cediranib maleate and olaparib and to see how well they work compared to olaparib alone in treating patients with ovarian, fallopian tube, peritoneal, or triple-negative breast cancer that has returned after a period of improvement (recurrent). Cediranib maleate may help keep cancer cells from growing by affecting their blood supply. Olaparib may stop cancer cells from growing abnormally. The combination of cediranib maleate and olaparib may be safe, tolerable and/or effective in treating patients with recurrent ovarian, fallopian tube, or peritoneal cancer or recurrent triple-negative breast cancer.

Conditions

Primary Peritoneal Serous Adenocarcinoma; Triple-Negative Breast Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Fallopian Tube Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian High Grade Serous Adenocarcinoma; Ovarian Serous Adenocarcinoma

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Dose Limiting Toxicities of Cediranib Maleate in Combination With Olaparib (Phase I)

  Was determined using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  At 28 days

• The Maximum Tolerated Dose (MTD) of Cediranib in Combination With Olaparib in the Treatment of Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Metastatic Triple-negative Breast Cancer (Phase I)

  This trial employed a 3+3 design, escalating on 0/3 or 1/6 DLT, and de-escalating if 2 DLTs were encountered. The MTD (maximum tolerated dose) was the dose at which no more than 1 patient developed a dose-limiting toxicity (DLT) when at least 6 patients had been treated.

  At 28 Days

• Progression-free Survival (PFS) at the Maximum Tolerated Dose/Recommended Phase 2 Dose of Cediranib Maleate With Olaparib Compared to That of Olaparib Alone (Phase II)

  Evaluated by Kaplan-Meier analysis and log-rank test for between group comparison, and median survival times reported. PFS is defined as time from randomization to investigator-assessed radiographic progression by RECIST 1.1 criteria or death. Patients alive without evidence of progression were censored at the last disease assessment.

  Time from start of treatment to time of objective disease progression, assessed up to 5 years

• The Maximum Tolerated Dose (MTD) of Cediranib in Combination With Olaparib Tablet Formulation in the Treatment of Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer (Phase I-T).

  The Phase 1-T component of this trial employed a 3+3 design, escalating on 0/3 or 1/6 DLT, and de-escalating if 2 DLTs were encountered. The MTD (maximum tolerated dose) was the dose at which no more than 1 patient developed a DLT when at least 6 patients had been treated.

  At 28 days

Secondary Outcomes (4)

• Number of Participants With Treatment-related Toxicities of the Combination of Cediranib Maleate and Olaparib (Phase I)

  Adverse Events monitored for 3 years, mortality assessed up to 5 years

• Tumor Response Rate (Objective Response Rate) Defined by Response Evaluation Criteria in Solid Tumors Criteria (Phase II)

  Up to 5 years

• Overall Survival (Phase II)

  Up to 5 years

• Number of Participants With Treatment-related Toxicities of the Combination of Cediranib and Olaparib (Tablet Formulation) in the Treatment of Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer (Phase I-T).

  Up to 3 years

Study Arms (2)

Arm I (cediranib maleate and olaparib)

EXPERIMENTAL

Patients receive cediranib maleate PO QD and olaparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo CT or MRI as well as blood sample collection on the trial. Patients may also optionally undergo a tissue biopsy on the trial.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Cediranib Maleate; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Drug: Olaparib

Arm II (olaparib)

ACTIVE COMPARATOR

Patients receive olaparib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo CT or MRI as well as blood sample collection on the trial. Patients may also optionally undergo a tissue biopsy on the trial.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Drug: Olaparib

Interventions

Cediranib Maleate DRUG

Given PO

Also known as: AZD2171, AZD2171 Maleate, Recentin

Arm I (cediranib maleate and olaparib)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm I (cediranib maleate and olaparib); Arm II (olaparib)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Arm I (cediranib maleate and olaparib); Arm II (olaparib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm I (cediranib maleate and olaparib); Arm II (olaparib)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281

Arm I (cediranib maleate and olaparib); Arm II (olaparib)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Arm I (cediranib maleate and olaparib); Arm II (olaparib)

Biopsy Procedure PROCEDURE

Undergo optional tissue biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Arm I (cediranib maleate and olaparib); Arm II (olaparib)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (cediranib maleate and olaparib); Arm II (olaparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PHASE I: Participants must have histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal serous cancer, fallopian tube cancer, or triple-negative breast cancer
• PHASE II: Participants must have histologically or cytologically grade 2 or 3 (high-grade) papillary-serous or endometrioid epithelial ovarian cancer, primary peritoneal serous cancer, or fallopian tube cancer; participants with epithelial ovarian, primary peritoneal, or fallopian tube cancers of other high-grade histologies who carry a known deleterious breast cancer gene (BRCA) germline mutation by standard clinical testing (Myriad BRAC Analysis) will also be considered eligible
• PHASE I-T: Participants must have histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal serous cancer, or fallopian tube cancer
• Ovarian cancer, primary peritoneal, and fallopian tube participants in the Phase 1 and Phase 1-T portions of this trial must have either measurable cancer by RECIST 1.1 criteria or an elevated cancer antigen (CA)125 level at least twice the upper limit of normal on two separate occasions at least 1 day but not more than 3 months apart; at least one of the samples should be within 1 week of starting treatment; patients with both an elevated CA125 and measurable cancer will be followed by RECIST 1.1 criteria; patients with only an elevated CA125 level will be followed by modified Gynecologic Cancer Intergroup (GCIG) criteria
• Participants in the Phase II portion of the trial must have measurable disease by RECIST 1.1 criteria
• Breast cancer participants must have measurable disease by RECIST criteria
• PRIOR THERAPY PHASE I and PHASE I-T:
• Prior chemotherapy for ovarian cancer patients must have included a first-line platinum-based regimen with or without intravenous consolidation chemotherapy
• Breast cancer patients must have recurred post both an Adriamycin- and taxane-containing regimen
• Prior hormonal-based therapy for ovarian, primary peritoneal serous, fallopian tube cancer, or breast cancer is acceptable
• Patients may not have had a prior PAR polymerase (PARP)-inhibitor in the recurrent or metastatic setting; prior treatment with BSI-201 (iniparib) is allowed
• Patients may not have had a prior anti-angiogenic agent in the recurrent or metastatic setting
• PRIOR THERAPY PHASE II:
• Prior chemotherapy must have included a first-line platinum-based regimen with or without intravenous consolidation chemotherapy
• Prior hormonal-based therapy for ovarian, primary peritoneal serous, or fallopian tube cancer is acceptable

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
• Participants may not be receiving any other investigational agents nor have participated in an investigational trial within the past 4 weeks; subjects may not have received prior treatment affecting the vascular endothelial growth factor (VEGF) pathway in the recurrent setting, including thalidomide, bevacizumab, sunitinib, or sorafenib; in the Phase I portion of the trial, subjects may not have received prior treatment with oregovomab (OvaRex) or any other antibodies that may interfere with CA-125 measurements
• Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or MRI scans should not be included on this study, since neurologic dysfunction may confound the evaluation of neurologic and other adverse events; 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 maleate 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; dihydropyridine calcium-channel blockers are permitted for management of hypertension
• Patients with any of the following:
• History of myocardial infarction within six months
• Patients with corrected QT (QTc) prolongation \> 500 msec or other significant electrocardiogram (ECG) abnormality noted within 14 days of treatment
• For patients enrolled in the Phase 1-T portion of the protocol, the QTc should not exceed 470 msec
• 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
• Condition requiring concurrent use of drugs or biologics with pro-arrhythmic potential
• History of stroke or transient ischemic attack within six months
• Patients may not have any evidence of pre-existing inadequately controlled hypertension (defined as a systolic blood pressure \[BP\] of \> 140 mmHg or a diastolic BP of \> 90 mmHg), and must have a normal blood pressure (=\< 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; patients who are on three antihypertensive medications must be actively followed by a cardiologist or blood pressure specialist for management of blood pressure while on protocol
• Any prior history of hypertensive crisis or hypertensive encephalopathy

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (14)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Fort Wayne Medical Oncology and Hematology Inc - Jefferson Boulevard

Fort Wayne, Indiana, 46804, United States

Location

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, 46845, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

National Cancer Institute

Rockville, Maryland, 20850, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (3)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

• Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, Luo W, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, Matulonis UA. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol. 2014 Oct;15(11):1207-14. doi: 10.1016/S1470-2045(14)70391-2. Epub 2014 Sep 10.

  PMID: 25218906 DERIVED

• Liu JF, Tolaney SM, Birrer M, Fleming GF, Buss MK, Dahlberg SE, Lee H, Whalen C, Tyburski K, Winer E, Ivy P, Matulonis UA. A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Eur J Cancer. 2013 Sep;49(14):2972-8. doi: 10.1016/j.ejca.2013.05.020. Epub 2013 Jun 27.

  PMID: 23810467 DERIVED

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Triple Negative Breast Neoplasms

Interventions

Biopsy; Specimen Handling; cediranib; Magnetic Resonance Spectroscopy; olaparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Dr. Joyce Liu
• Organization: Dana-Farber Cancer Institute

joyce_liu@dfci.harvard.edu

617-632-5269

Study Officials

• Joyce F Liu

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2010
• First Posted: May 5, 2010
• Study Start: April 14, 2010
• Primary Completion: October 31, 2018
• Study Completion (Estimated): March 4, 2027
• Last Updated: May 4, 2026
• Results First Posted: July 22, 2020

Record last verified: 2026-03

Locations

US (14)