Clinical Trials /

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

NCT04739800

Description:

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.

Related Conditions:
  • Fallopian Tube Clear Cell Adenocarcinoma
  • Fallopian Tube Endometrioid Adenocarcinoma
  • Fallopian Tube Mucinous Adenocarcinoma
  • Fallopian Tube Transitional Cell Carcinoma
  • Fallopian Tube Undifferentiated Carcinoma
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Low Grade Fallopian Tube Serous Adenocarcinoma
  • Low Grade Ovarian Serous Adenocarcinoma
  • Ovarian Clear Cell Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Mixed Epithelial Tumor
  • Ovarian Mucinous Adenocarcinoma
  • Ovarian Transitional Cell Carcinoma
  • Ovarian Undifferentiated Carcinoma
  • Primary Peritoneal Clear Cell Carcinoma
  • Primary Peritoneal Endometrioid Adenocarcinoma
  • Primary Peritoneal High Grade Serous Adenocarcinoma
  • Primary Peritoneal Low Grade Serous Adenocarcinoma
  • Primary Peritoneal Transitional Cell Carcinoma
  • Primary Peritoneal Undifferentiated Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Comparison of Standard of Care Treatment With a Triplet Combination of Targeted Immunotherapeutic Agents
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: NCI-2021-00615
  • SECONDARY ID: NCI-2021-00615
  • SECONDARY ID: NRG-GY023
  • SECONDARY ID: NRG-GY023
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT04739800

Conditions

  • Fallopian Tube Mucinous Adenocarcinoma
  • Ovarian Seromucinous Carcinoma
  • Platinum-Refractory Fallopian Tube Carcinoma
  • Platinum-Refractory Ovarian Carcinoma
  • Platinum-Refractory Primary Peritoneal Carcinoma
  • Recurrent Fallopian Tube Clear Cell Adenocarcinoma
  • Recurrent Fallopian Tube Endometrioid Adenocarcinoma
  • Recurrent Fallopian Tube Mucinous Adenocarcinoma
  • Recurrent Fallopian Tube Transitional Cell Carcinoma
  • Recurrent Fallopian Tube Undifferentiated Carcinoma
  • Recurrent High Grade Fallopian Tube Serous Adenocarcinoma
  • Recurrent High Grade Ovarian Serous Adenocarcinoma
  • Recurrent Low Grade Fallopian Tube Serous Adenocarcinoma
  • Recurrent Low Grade Ovarian Serous Adenocarcinoma
  • Recurrent Ovarian Clear Cell Adenocarcinoma
  • Recurrent Ovarian Endometrioid Adenocarcinoma
  • Recurrent Ovarian Mucinous Adenocarcinoma
  • Recurrent Ovarian Seromucinous Carcinoma
  • Recurrent Ovarian Transitional Cell Carcinoma
  • Recurrent Ovarian Undifferentiated Carcinoma
  • Recurrent Platinum-Resistant Fallopian Tube Carcinoma
  • Recurrent Platinum-Resistant Ovarian Carcinoma
  • Recurrent Platinum-Resistant Primary Peritoneal Carcinoma
  • Recurrent Primary Peritoneal Clear Cell Adenocarcinoma
  • Recurrent Primary Peritoneal Endometrioid Adenocarcinoma
  • Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma
  • Recurrent Primary Peritoneal Low Grade Serous Adenocarcinoma
  • Recurrent Primary Peritoneal Transitional Cell Carcinoma
  • Recurrent Primary Peritoneal Undifferentiated Carcinoma
  • Refractory Fallopian Tube Clear Cell Adenocarcinoma
  • Refractory Fallopian Tube Endometrioid Adenocarcinoma
  • Refractory Fallopian Tube Mucinous Adenocarcinoma
  • Refractory Fallopian Tube Transitional Cell Carcinoma
  • Refractory Fallopian Tube Undifferentiated Carcinoma
  • Refractory High Grade Fallopian Tube Serous Adenocarcinoma
  • Refractory High Grade Ovarian Serous Adenocarcinoma
  • Refractory Low Grade Fallopian Tube Serous Adenocarcinoma
  • Refractory Low Grade Ovarian Serous Adenocarcinoma
  • Refractory Ovarian Clear Cell Adenocarcinoma
  • Refractory Ovarian Endometrioid Adenocarcinoma
  • Refractory Ovarian Mucinous Adenocarcinoma
  • Refractory Ovarian Seromucinous Carcinoma
  • Refractory Ovarian Transitional Cell Carcinoma
  • Refractory Ovarian Undifferentiated Carcinoma
  • Refractory Primary Peritoneal Clear Cell Adenocarcinoma
  • Refractory Primary Peritoneal Endometrioid Adenocarcinoma
  • Refractory Primary Peritoneal High Grade Serous Adenocarcinoma
  • Refractory Primary Peritoneal Low Grade Serous Adenocarcinoma
  • Refractory Primary Peritoneal Transitional Cell Carcinoma
  • Refractory Primary Peritoneal Undifferentiated Carcinoma

Interventions

DrugSynonymsArms
Cediranib MaleateAZD2171, AZD2171 Maleate, RecentinArm II (durvalumab, cediranib maleate, olaparib)
DurvalumabImfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Arm II (durvalumab, cediranib maleate, olaparib)
OlaparibAZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281Arm II (durvalumab, cediranib maleate, olaparib)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratArm I (paclitaxel, doxorubicin, topotecan hydrochloride))
Pegylated Liposomal Doxorubicin HydrochlorideATI-0918, Caelyx, Dox-SL, Doxil, Doxilen, Doxorubicin HCl Liposomal, Doxorubicin HCl Liposome, Doxorubicin Hydrochloride Liposome, Duomeisu, Evacet, LipoDox, Lipodox 50, Liposomal Adriamycin, Liposomal Doxorubicin Hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))
Topotecan HydrochlorideHycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl, topotecan hydrochloride (oral)Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and
      cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by
      progression-free survival (PFS), as compared to physician's choice standard of care
      chemotherapy, in patients with recurrent platinum-resistant ovarian, primary peritoneal or
      fallopian tube cancer who had prior bevacizumab.

      SECONDARY OBJECTIVES:

      I. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and
      cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by
      overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version
      1.1, as compared to physician's choice standard of care chemotherapy, in patients with
      recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube cancer who had
      prior bevacizumab.

      II. To assess the efficacy of the combinations durvalumab (MEDI4736) plus olaparib and
      cediranib, durvalumab (MEDI4736) plus cediranib, or olaparib and cediranib, as measured by
      overall survival (OS), as compared to physician's choice standard of care chemotherapy, in
      patients with recurrent platinum-resistant ovarian, primary peritoneal or fallopian tube
      cancer who had prior bevacizumab.

      OUTLINE: Patients are randomized to 1 of 4 arms.

      ARM I: Patients receive paclitaxel intravenously (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.

      ARM II: Patients receive durvalumab IV over 60 minutes on day 1, cediranib maleate orally
      (PO) once daily (QD) Monday through Friday, and olaparib PO twice daily (BID) on days 1-28.
      Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

      ARM III: 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.

      ARM IV: 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.

      After completion of study treatment, patients are followed up periodically for up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (paclitaxel, doxorubicin, topotecan hydrochloride))Active ComparatorPatients 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.
  • Paclitaxel
  • Pegylated Liposomal Doxorubicin Hydrochloride
  • Topotecan Hydrochloride
Arm II (durvalumab, cediranib maleate, olaparib)ExperimentalPatients 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.
  • Cediranib Maleate
  • Durvalumab
  • Olaparib
Arm III (durvalumab, cediranib maleate)ExperimentalPatients 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.
  • Cediranib Maleate
  • Durvalumab
Arm IV (cediranib maleate, olaparib)ExperimentalPatients 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.
  • Cediranib Maleate
  • Olaparib

Eligibility Criteria

        Inclusion Criteria:

          -  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, mucinous or transitional cell carcinoma
             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 BRCA testing through Myriad, Myriad testing
                  will be accepted. 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 showed
                  a recognized germ line deleterious BRCA 1 or BRCA 2 mutation or BRCA
                  rearrangement is required. A copy of Myriad or other BRCA mutational analysis
                  (positive or variant of unknown significance [VUS] or negative) reports will be
                  required for study enrollment

          -  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 >= 2x
             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 =< 1.5 x institutional/laboratory upper limit of normal (ULN) OR measured
             creatinine clearance > 50 mL/min/1.73 m^2

          -  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 protein of =< 500mg over 24 hours

          -  Total serum bilirubin level =< 1.5 x ULN (patients with known Gilbert's disease who
             have bilirubin level =< 3 x ULN may be enrolled)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN

          -  Age >= 18 years

          -  Body weight > 30 kg

          -  Adequately controlled blood pressure (systolic blood pressure [SBP] =< 140; diastolic
             blood pressure [DBP] =< 90 mmHg) on a maximum of three antihypertensive medications.
             Patients must have a BP of =< 140/90 mmHg taken in the clinic setting by a medical
             professional within 2 weeks prior to study registration. It is strongly recommended
             that patients who are on three antihypertensive medications be followed by a
             cardiologist or a primary care physician for management of BP while on protocol.
             Patients must be willing and able to check and record daily blood pressure readings.
             BP cuffs will be provided to patients randomized to the cediranib-containing arms

          -  Adequately controlled thyroid dysfunction with no symptoms of thyroid dysfunction and
             normal thyroid stimulating hormone (TSH). If TSH is not within normal range despite no
             symptoms of thyroid dysfunction, normal free T4 level is required

          -  Able to swallow and retain oral medications and no gastrointestinal (GI) illnesses
             that would preclude absorption of olaparib and cediranib as judged by treating
             physician

          -  Toxicities of prior therapy (excepting alopecia and vitiligo), should be resolved to
             less than or equal to grade 1 as per Common Terminology Criteria for Adverse Events
             (CTCAE) v5.0

          -  Women of childbearing potential (WOCBP) must agree to use two forms of birth control
             (hormonal or barrier method of birth control; abstinence). Note: Definition of women
             of no longer having childbearing potential: Postmenopausal or evidence of
             non-childbearing status for women of childbearing potential as confirmed by a negative
             urine or serum pregnancy test within 7 days prior to start of study treatment.
             Postmenopausal is defined as: Age >= 60 years, or age < 60 with any one or more of the
             conditions below:

               -  Amenorrhoeic for >= 1 year in the absence of chemotherapy and/or hormonal
                  treatments,

               -  Luteinizing hormone and/or follicle stimulating hormone and/or estradiol levels
                  in the post-menopausal range,

               -  Radiation-induced oophorectomy with last menses > 1 year ago,

               -  Chemotherapy-induced menopause with > 1 year interval since last menses,

               -  Surgical sterilization (bilateral oophorectomy or hysterectomy)

          -  The patient or a legally authorized representative must provide study-specific
             informed consent prior to study entry and authorization permitting release of personal
             health information

        Exclusion Criteria:

          -  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 had prior PARP inhibitor or immune checkpoint blockade
                  requiring dose modifications as they cannot start this study 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)

          -  Pregnant women. Because there is an unknown but potential risk of adverse events in
             nursing infants secondary to treatment of the mother with these drugs, breastfeeding
             should be discontinued. These potential risks may also apply to other agents used in
             this study

          -  Patients with a prior or concurrent malignancy whose natural history or treatment does
             not have the potential to interfere with the safety or efficacy assessment of the
             investigational regimen are eligible for this trial

          -  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,
             since neurologic dysfunction may confound the evaluation of neurologic and other
             adverse events. 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 registration

          -  Patients who have the following clinical conditions are considered to be at increased
             risk for cardiac toxicities. Patients with any cardiac history of the following
             conditions:

               -  History of myocardial infarction or myocarditis within six months of study
                  registration

               -  Unstable angina

               -  Resting electrocardiogram (ECG) with clinically significant abnormal findings.

               -  New York Heart Association functional 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 or T-DM1

               -  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 of study registration

          -  Clinically significant peripheral vascular disease or vascular disease (aortic
             aneurysm or aortic dissection)

          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the
             first dose of study treatment. Patients must have recovered from any effects of any
             major surgery and surgical wound should have healed prior to starting treatment. Note:
             Local surgery of isolated lesions for palliative intent is acceptable

          -  Evidence of coagulopathy or bleeding diathesis. Therapeutic anticoagulation for prior
             thromboembolic events, including warfarin, is permitted. Patients receiving warfarin
             are recommended to have careful monitoring of international normalized ratio (INR)

          -  Evidence 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)

          -  Human immunodeficiency virus (HIV) positive patients due to potential drug and drug
             interactions

          -  Patients may not use any complementary or alternative medicines including natural
             herbal products or folk remedies as they may interfere with the effectiveness of the
             study treatments

          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of study
             treatment. Note: Patients, if enrolled, should not receive live vaccine whilst
             receiving study treatment and up to 30 days after the last dose of study treatment

          -  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

          -  Patients receiving any medications or substances that are strong inhibitors or
             inducers of CYP3A4. Dihydropyridine calcium-channel blockers are permitted for
             management of hypertension

          -  Current or prior use of immunosuppressive medication within 14 days of study
             registration. The following are exceptions to this criterion:

               -  Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
                  articular injection)

               -  Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
                  prednisone or its equivalent

               -  Steroids as premedication for hypersensitivity reactions (e.g., CT scan
                  premedication)

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to durvalumab, olaparib, or cediranib

          -  Patients with active autoimmune disease that has required systemic treatment in the
             past 2 years (i.e., with use of disease modifying agents, corticosteroids, or
             immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,
             etc.) is not considered a form of systemic treatment

          -  Active infection including tuberculosis (clinical evaluation that includes clinical
             history, physical examination and radiographic findings, and tuberculosis [TB] testing
             in line with local practice), hepatitis B (known positive hepatitis B virus [HBV]
             surface antigen (HBsAg) result), or hepatitis C. Patients with a past or resolved HBV
             infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence
             of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible
             only if polymerase chain reaction is negative for hepatitis C virus (HCV) ribonucleic
             acid (RNA)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:From study entry to time of progression or death, whichever occurs first, assessed up to 5 years
Safety Issue:
Description:Will be presented by Kaplan Meier methods.

Secondary Outcome Measures

Measure:Objective response rate
Time Frame:From the start of the treatment until disease progression/recurrence, assessed up to 5 years
Safety Issue:
Description:Quantified as the binomial proportion of patients with measurable disease at enrollment who have a best overall response of complete response (CR) or partial response (PR).
Measure:Duration of response
Time Frame:From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years
Safety Issue:
Description:Will be presented by Kaplan Meier methods.
Measure:Overall survival
Time Frame:Time from study entry to date of death from any cause, assessed up to 5 years
Safety Issue:
Description:Will be presented by Kaplan Meier methods.
Measure:Incidence of adverse events
Time Frame:Up to 30 days post treatment
Safety Issue:
Description:All adverse events, including severe adverse events and treatment-related adverse events, will be categorized and graded for severity according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

August 25, 2021