NCT04739800|Active Not RecruitingPhase 2ResultsFDA Drug

Comparison of Standard of Care Treatment With a Triplet Combination of Targeted Immunotherapeutic Agents

A Randomized Phase II Trial of Triplet Therapy (A PD-L1 Inhibitor Durvalumab (MEDI4736) in Combination With Olaparib and Cediranib) Compared to Olaparib and Cediranib or Durvalumab (MEDI4736) and Cediranib or Standard of Care Chemotherapy in Women With Platinum-Resistant Recurrent Epithelial Ovarian Cancer, Primary Peritoneal or Fallopian Cancer Who Have Received Prior Bevacizumab

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2021-00615NRG-GY023U10CA180868

Study Type

interventional

Target

120

Locations

2 countries

Sites

393

Timeline

RegisteredFeb 2021

StartedJun 2021

CompletionMar 2027

Brief Summary

This phase II trial studies the possible benefits of treatment with different combinations of the drugs durvalumab, olaparib and cediranib vs. the usual treatment in patients with ovarian, primary peritoneal, or fallopian tube cancer that has come back after a period of improvement with platinum therapy (recurrent platinum resistant). Usual treatment is the type of treatment most patients with this condition receive if they are not part of a clinical study. Combination therapies studied in this trial include MEDI4736 (durvalumab) plus olaparib and cediranib, durvalumab and cediranib, or olaparib and cediranib. Monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumors cells to grow and spread. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Cediranib may stop the growth of tumor cells by blocking VEGF (an enzyme). needed for cell growth. Giving different combinations of durvalumab, olaparib and cediranib may work better in increasing the duration of time that the cancer does not progress compared to the usual treatment.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

120

participants targeted

Target at P50-P75 for phase_2

Timeline

10mo left

Started Jun 2021

Longer than P75 for phase_2

Geographic Reach

2 countries

393 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.7 years study duration

Study Progress86%

Jun 2021Mar 2027

First Submitted

Initial submission to the registry

February 4, 2021

Completed

1 day until next milestone

First Posted

Study publicly available on registry

February 5, 2021

Completed

4 months until next milestone

Study Start

First participant enrolled

June 10, 2021

Completed

1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 26, 2023

Completed

1.4 years until next milestone

Results Posted

Study results publicly available

June 18, 2024

Completed

2.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 4, 2027

Expected

Last Updated

April 13, 2026

Status Verified

March 1, 2026

Enrollment Period

1.6 years

First QC Date

February 4, 2021

Results QC Date

March 27, 2024

Last Update Submit

April 9, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

Progression Free Survival
The relationship of randomized treatment assignment to progression free survival. The RECIST 1.1 criteria are used for disease progression. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
From start of treatment to time of progression or death, whichever occurs first. Median follow-up time was 4.8 months (Inter-Quartile Range: 2.0-7.9 months).

Secondary Outcomes (4)

Objective Response Rate
From the start of the treatment until disease progression/recurrence, or termination by the DMC. The median followup time was 4.3 months. The maximum followup time was 11 months. Patients are no longer being assessed.
Duration of Response
Throughout study treatment, up to 10.6 months.
Overall Survival
Time from study entry to date of death from any cause, or termination by the DMC. The median followup time was 4.3 months. The maximum followup time was 11 months. Patients are no longer being assessed.
Count of Participants With a Grade 3 (or Higher) Adverse Event
From the start of treatment until disease progression/recurrence or termination by the DMC. The median followup time was 4.3 months. The maximum followup time was 11 months. Patients are no longer being assessed.

Study Arms (4)

Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))

ACTIVE COMPARATOR

Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, or pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, or topotecan hydrochloride IV over 30 minutes on days 1, 8 and 15 or days 1-5 per the discretion of the treating physician. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

Procedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Computed Tomography with ContrastProcedure: Echocardiography TestProcedure: Magnetic Resonance ImagingProcedure: Multigated Acquisition ScanDrug: PaclitaxelDrug: Pegylated Liposomal Doxorubicin HydrochlorideDrug: Topotecan Hydrochloride

Arm II (durvalumab, cediranib maleate, olaparib)

EXPERIMENTAL

Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate PO QD Monday through Friday, and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

Procedure: Biospecimen CollectionDrug: Cediranib MaleateProcedure: Computed TomographyProcedure: Computed Tomography with ContrastBiological: DurvalumabProcedure: Echocardiography TestProcedure: Magnetic Resonance ImagingProcedure: Multigated Acquisition ScanDrug: Olaparib

Arm III (durvalumab, cediranib maleate)

EXPERIMENTAL

Patients receive durvalumab IV over 60 minutes on day 1 and cediranib maleate PO QD Monday through Friday. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

Arm IV (cediranib maleate, olaparib)

EXPERIMENTAL

Patients receive cediranib maleate PO QD on days 1-28 and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo ECHO or MUGA during screening and as clinically indicated on study. Patients also undergo collection of blood and CT with contrast during screening, and CT or MRI scans throughout the trial.

Procedure: Biospecimen CollectionDrug: Cediranib MaleateProcedure: Computed TomographyProcedure: Computed Tomography with ContrastProcedure: Echocardiography TestProcedure: Magnetic Resonance ImagingDrug: Olaparib

Interventions

Magnetic Resonance ImagingPROCEDURE

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 (paclitaxel, doxorubicin, topotecan hydrochloride))Arm II (durvalumab, cediranib maleate, olaparib)Arm III (durvalumab, cediranib maleate)Arm IV (cediranib maleate, olaparib)

PaclitaxelDRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))

Topotecan HydrochlorideDRUG

Given IV

Also known as: Evotopin, Hycamptamine, Hycamtin, Nogitecan Hydrochloride, Potactasol, SKF S 104864 A, SKF S-104864-A, SKF S104864A, Topotec, Topotecan HCl, topotecan hydrochloride (oral)

Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))

Multigated Acquisition ScanPROCEDURE

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 (paclitaxel, doxorubicin, topotecan hydrochloride))Arm II (durvalumab, cediranib maleate, olaparib)Arm III (durvalumab, cediranib maleate)

DurvalumabBIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736, MEDI4736

Arm II (durvalumab, cediranib maleate, olaparib)Arm III (durvalumab, cediranib maleate)

Pegylated Liposomal Doxorubicin HydrochlorideDRUG

Given IV

Also known as: ATI-0918, Caelyx, Dox-SL, Doxil, Doxilen, Doxorubicin HCl Liposomal, Doxorubicin HCl Liposome, Doxorubicin Hydrochloride Liposome, Doxorubicin Liposomal, Duomeisu, Evacet, LipoDox, Lipodox 50, Liposomal Adriamycin, Liposomal Doxorubicin Hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, Pegylated Liposomal Doxorubicin, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99

Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))

Computed TomographyPROCEDURE

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 (paclitaxel, doxorubicin, topotecan hydrochloride))Arm II (durvalumab, cediranib maleate, olaparib)Arm III (durvalumab, cediranib maleate)Arm IV (cediranib maleate, olaparib)

Computed Tomography with ContrastPROCEDURE

Undergo CT with contrast

Also known as: Contrast Enhanced Computed Tomography, CONTRAST ENHANCED CT SCAN, Contrast-enhanced Computed Tomography, CT Scan With Contrast, CT with Contrast

Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Arm II (durvalumab, cediranib maleate, olaparib)Arm III (durvalumab, cediranib maleate)Arm IV (cediranib maleate, olaparib)

Echocardiography TestPROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Arm II (durvalumab, cediranib maleate, olaparib)Arm III (durvalumab, cediranib maleate)Arm IV (cediranib maleate, olaparib)

OlaparibDRUG

Given PO

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

Arm II (durvalumab, cediranib maleate, olaparib)Arm IV (cediranib maleate, olaparib)

Biospecimen CollectionPROCEDURE

Undergo collection of blood

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

Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Arm II (durvalumab, cediranib maleate, olaparib)Arm III (durvalumab, cediranib maleate)Arm IV (cediranib maleate, olaparib)

Cediranib MaleateDRUG

Given PO

Also known as: AZD2171, AZD2171 Maleate, Recentin

Arm II (durvalumab, cediranib maleate, olaparib)Arm III (durvalumab, cediranib maleate)Arm IV (cediranib maleate, olaparib)

Eligibility Criteria

Age18 Years+

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Women with recurrent/persistent platinum-resistant ovarian, primary peritoneal, or fallopian tube cancers; platinum-resistant disease is defined as progression within \< 6 months from completion of platinum based therapy. The date should be calculated from the last administered dose of platinum therapy
Patients must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer and must have a histological diagnosis of high grade serous, grade 3 endometrioid or clear cell carcinoma based on local histopathological findings. Patients with low grade serous, grade 1 or 2 endometrioid, mixed epithelial, undifferentiated carcinoma, or mucinous carcinoma histologies are also eligible, provided that the patient has a known deleterious BRCA1 or BRCA2 mutation identified through testing at a clinical laboratory. Histologic confirmation of the original primary tumor is required via the pathology report (upload of report required). Confirmation of BRCA1 and BRCA2 germline and/or somatic mutation status and hormone receptor (HR) status is required for all entered patients (if available) via testing report (upload of report\[s\] required)
Evaluable disease - defined as RECIST 1.1 measurable disease OR non-measurable 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 in the setting of a CA125 \>= 2 x upper limit of normal \[ULN\])
Prior therapy:
At least two prior treatment regimens (including primary therapy) but up to 5 lines of systemic anticancer therapy. Hormonal therapy (such as tamoxifen, aromatase inhibitors) will not count as a previous treatment regimen.
Prior use of bevacizumab in the upfront or recurrent setting is required.
Prior use of PARP inhibitor is allowed.
Prior use of immune checkpoint blockade (e.g., a PD-L1/PD-1inhibitor or a CTLA-4 inhibitor) is allowed
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Absolute neutrophil count (ANC) \>= 1,500/mcL
Hemoglobin \> 10 g/dL
Platelets \>= 100,000/mcL
Creatinine clearance (CrCL) or estimated glomerular filtration rate (eGFR) of \> 50 mL/min estimated using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR)
Urine protein: creatinine ratio (UPC) of =\< 1
Total serum bilirubin level =\< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =\< 3 x ULN may be enrolled)
+14 more criteria

You may not qualify if:

Primary platinum-refractory disease defined as progression during first-line platinum-based chemotherapy
Rising CA-125 only without RECIST 1.1 evaluable disease
Prior therapy:
Patients who have had chemotherapy, investigational drugs or radiotherapy within 3 weeks prior to study registration or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
Patients may not have had hormonal therapy within 2 weeks of study registration. Patients receiving raloxifene for bone health as per Food and Drug Administration (FDA) indication may remain on raloxifene absent other drug interactions.
Prior use of concurrent olaparib and cediranib combination.
Patients who have experienced immune-mediated adverse events requiring dose modification or discontinuation.
For patients who have received prior PARP inhibitor:
Patients who have required dose modification or dose reduction of olaparib will not be eligible, as they will not be able to start this study at full dose.
Patients who have required dose reduction of non-olaparib PARP inhibitors for hematologic adverse events will not be eligible (Note: niraparib that is initiated at 200mg daily per weight and platelet guidelines is not considered a dose reduction).
Patients who required dose-reduction of non-olaparib PARP inhibitors for non-hematologic adverse events may be eligible after discussion with the Study Chair if the treating investigator feels that they could appropriately receive olaparib at full dose.
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 3 months prior to study registration
Current signs and/or symptoms of bowel obstruction or signs and/or symptoms of bowel obstruction within 3 months of study registration except temporary (\< 24 hr) improved with medical management, within last 3 months
Any prior grade \>= 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \> grade 1
Dependency on IV hydration or total parenteral nutrition (TPN)
+32 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

NRG Oncologycollaborator
National Cancer Institute (NCI)lead

Study Sites (393)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC