Clinical Trials /

Pegylated Liposomal Doxorubicin Hydrochloride With Atezolizumab and/or Bevacizumab in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

NCT02839707

Description:

This randomized phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab and bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known which combination will work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Peritoneal Carcinoma
Recruiting Status:

Suspended

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Pegylated Liposomal Doxorubicin Hydrochloride With Atezolizumab and/or Bevacizumab in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
  • Official Title: A Randomized, Phase II/III Study of Pegylated Liposomal Doxorubicin and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin/Bevacizumab and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin/Bevacizumab in Platinum Resistant Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: NCI-2016-01081
  • SECONDARY ID: NCI-2016-01081
  • SECONDARY ID: NRG-GY009
  • SECONDARY ID: NRG-GY009
  • SECONDARY ID: NRG-GY009
  • SECONDARY ID: U10CA180868
  • SECONDARY ID: UG1CA189867
  • NCT ID: NCT02839707

Conditions

  • Fallopian Tube Clear Cell Adenocarcinoma
  • Fallopian Tube Endometrioid Adenocarcinoma
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Ovarian Clear Cell Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Seromucinous Carcinoma
  • Primary Peritoneal High Grade Serous Adenocarcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma
  • Undifferentiated Fallopian Tube Carcinoma
  • Undifferentiated Ovarian Carcinoma

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqArm I (PLD, atezolizumab)
BevacizumabAnti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar FKB238, BEVACIZUMAB, LICENSE HOLDER UNSPECIFIED, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGFArm II (PLD, bevacizumab, atezolizumab)
Pegylated Liposomal Doxorubicin HydrochlorideATI-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-99Arm I (PLD, atezolizumab)

Purpose

This randomized phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. block tumor growth Monoclonal antibodies, such as atezolizumab and bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known which combination will work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Estimate the probability of a dose limiting toxicity (DLT) following cycle 1 of
      experimental regimens (pegylated liposomal doxorubicin hydrochloride [pegylated liposomal
      doxorubicin] [PLD] and atezolizumab and PLD/bevacizumab and atezolizumab). (Safety lead-in)
      II. Estimate and compare the hazard of first progression or death (progression free survival
      [PFS]) of each experimental regimen relative to the reference regimen, PLD and bevacizumab.
      (Phase II study) III. Estimate and compare the hazard of death and the hazard of first
      progression or death (PFS) of each experimental regimen relative to the reference regimen.
      (Phase III)

      SECONDARY OBJECTIVES:

      I. Estimate and compare the probabilities of response rate (objective response rate [ORR],
      either partial or complete response) defined by Response Evaluation Criteria in Solid Tumors
      (RECIST) version (v)1.1 criteria on each study regimen. (Phase II study) II. Estimate the
      frequency and severity of adverse events as classified and graded with Common Terminology
      Criteria for Adverse Events (CTCAE) in those patients who initiate their randomly assigned
      study treatment. (Phase II study) III. Estimate and compare ORR in each treatment group.
      (Phase III study) IV. Estimate the frequency and severity of adverse events in those patients
      who initiate their randomly assigned study treatment. (Phase III study) V. Estimate and
      compare mean patient reported outcome scores (PROs) as measured by National Comprehensive
      Cancer Network (NCCN)-Functional Assessment of Cancer Therapy (FACT) ovarian symptom index
      (NFOSI)-18 disease-related symptoms (DRS). (Phase III study) VI. Estimate and compare the
      treatment groups on the basis of the PROs: treatment side effects (TSE), function/well-being
      (FWB), fatigue (Functional Assessment of Chronic Illness Therapy [FACIT]-fatigue [F]
      subscale) and abdominal discomfort (FACT/Gynecologic Oncology Group [GOG]-abdominal
      discomfort [AD] subscale). (Phase III study)

      TERTIARY OBJECTIVES:

      I. To determine whether biomarker levels in pre-treatment tissue, and pre- or on-treatment
      peripheral blood, and stool specimens are associated with ORR, PFS and/or overall survival
      (OS).

      II. To determine whether changes in quantitative biomarker parameters after the first 6 and
      12 weeks of therapy predict ORR, PFS and/or OS.

      OUTLINE: Patients will be randomized to 1 of 3 arms.

      ARM I: Patients receive pegylated liposomal doxorubicin hydrochloride intravenously (IV) over
      60 minutes on day 1 and atezolizumab IV over 30-60 minutes on days 1 and 15.

      ARM II: Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on
      day 1, bevacizumab IV over 30-90 minutes on days 1 and 15, and atezolizumab IV over 30-60
      minutes on days 1 and 15.

      ARM III: Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on
      day 1 and bevacizumab IV over 30-90 minutes on days 1 and 15.

      In all arms, courses repeat every 28 days in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for up to 2
      years, then every 6 months for up to 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (PLD, atezolizumab)ExperimentalPatients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 and atezolizumab IV over 30-60 minutes on days 1 and 15.
  • Atezolizumab
  • Pegylated Liposomal Doxorubicin Hydrochloride
Arm II (PLD, bevacizumab, atezolizumab)ExperimentalPatients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, bevacizumab IV over 30-90 minutes on days 1 and 15, and atezolizumab IV over 30-60 minutes on days 1 and 15.
  • Atezolizumab
  • Pegylated Liposomal Doxorubicin Hydrochloride
Arm III (PLD, bevacizumab)Active ComparatorPatients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 and bevacizumab IV over 30-90 minutes on days 1 and 15.
  • Pegylated Liposomal Doxorubicin Hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have the psychological ability and general health that permits
             completion of the study requirements and required follow up

          -  Women of child-bearing potential (WOCBP) 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 for 5 months (150 days) after the last dose
             of study agent; should a woman become pregnant or suspect she is pregnant while she is
             participating in this study, she should inform her treating physician immediately

          -  Submission of tumor tissue is required for all patients; investigators should check
             with their site pathology department regarding release of biospecimens before
             approaching patients about participation in the trial

          -  High grade ovarian cancer, including high grade serous; clear cell; endometrioid,
             grade 3; and others (adenocarcinoma, nitric oxide synthase [NOS]; mixed epithelial
             carcinoma; undifferentiated carcinoma); NOTE: low grade serous, mucinous and
             carcinosarcoma histologies are excluded; ovarian cancer = ovarian, fallopian tube or
             primary peritoneal cancer; required data element: submission of pathology report

          -  Recurrent, platinum resistant ovarian cancer (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)

          -  1-2 prior regimens (including primary therapy); hormonal therapies (e.g., tamoxifen,
             aromatase inhibitors) will not count toward the prior regimen limit

          -  Measurable disease (defined by RECIST v. 1.1) 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 in the setting of cancer antigen
             [CA]25 >= 2 x upper limit of normal [ULN])

          -  Performance status 0, 1 or 2

          -  Within 14 days prior to registration: Absolute neutrophil count (ANC) >= 1,500/mcl

          -  Within 14 days prior to registration: Platelets >= 100,000/mcl

          -  Within 14 days prior to registration: Hemoglobin (Hgb) >= 8 g/dl

          -  Within 14 days prior to registration: Creatinine =< 1.5 x institutional upper limit of
             normal (ULN)

          -  Within 14 days prior to registration: Urine protein creatinine (UPC) ratio must be <
             1.0 gm; if UPC ratio >= 1, collection of 24-hour urine measurement of urine protein is
             recommended (24-hour urine protein level must be < 1000 mg for patient enrollment);
             UPC ratio of spot urine is an estimation of the 24-hour urine protein excretion - a
             UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm

          -  Within 14 days prior to registration: Total Bilirubin =< 1.5 x ULN (patients with
             known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled)

          -  Within 14 days prior to registration: Aspartate aminotransferase (AST)/alanine
             aminotransferase (ALT) =< 3 x ULN (AST and/or ALT =< 5 x ULN for patients with liver
             involvement)

          -  International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
             =< 1.5 x ULN (or on stable dose of therapeutic anticoagulation, such as
             low-molecular-weight heparin, warfarin or rivaroxaban)

          -  Thyroid-stimulating hormone (TSH) within normal limits (TSH < ULN allowed in euthyroid
             patients on thyroid replacement therapy)

          -  The patient or legally authorized representative must provide study-specific informed
             consent prior to study entry and, for patients treated in the United States (U.S.),
             authorization permitting release of personal health information

        Exclusion Criteria:

          -  Patients with prior allogeneic bone marrow transplantation or prior solid organ
             transplantation

          -  Patients who have had systemic anticancer therapy (e.g., chemotherapy, targeted
             therapy) within 3 weeks prior to entering the study

          -  Patients who have had hormonal therapy (e.g., tamoxifen, aromatase inhibitor) within 1
             week prior to entering the study

          -  Patients with prior treatment with anti-programmed cell death (PD)-1, anti- programmed
             cell death ligand (PD-L)1 or anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4
             therapeutic antibody or other similar agents

          -  Patients with prior treatment with bevacizumab (or any other anti vascular therapy,
             e.g., cediranib) for platinum resistant recurrence; (Note: prior bevacizumab in
             initial therapy and/or platinum sensitive recurrent setting is allowed)

          -  Patients with prior treatment with PLD

          -  Prior radiotherapy to the abdomen or pelvis

          -  Patients who have not recovered from adverse events to < grade 1 (other than alopecia)
             due to agents administered more than 3 weeks earlier; however, the following therapies
             are allowed:

               -  Hormone replacement therapy or oral contraceptives

               -  Herbal therapy > 1 week prior to cycle 1, day 1 (herbal therapy intended as
                  anticancer therapy must be discontinued at least 1 week prior to cycle 1, day 1)

               -  Palliative radiotherapy for bone metastases > 2 weeks prior to cycle 1, day 1

          -  Treatment with any other investigational agent within 4 weeks prior to cycle 1, day 1

          -  Treatment with systemic immunostimulatory agents (including, but not limited to,
             interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to cycle 1, day 1

          -  Treatment with systemic immunosuppressive medications (including, but not limited to,
             prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor
             necrosis factor [anti-TNF] agents) within 2 weeks prior to cycle 1, day 1

               -  Patients who have received acute, low dose, systemic immunosuppressant
                  medications (e.g., a one-time dose of dexamethasone for nausea or steroids as
                  computed tomography [CT] scan contrast premedication) may be enrolled

               -  The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
                  for patients with orthostatic hypotension or adrenocortical insufficiency is
                  allowed

          -  Patients taking bisphosphonate therapy for symptomatic hypercalcemia within the past
             28 days; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or
             osteoporosis) is allowed

          -  Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS
             metastases are excluded, with the following exceptions:

               -  Patients with asymptomatic untreated CNS disease may be enrolled, provided all of
                  the following criteria are met:

                    -  Evaluable or measurable disease outside the CNS

                    -  No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within
                       10 mm of the optic apparatus (optic nerves and chiasm)

                    -  No history of intracranial hemorrhage or spinal cord hemorrhage

                    -  No ongoing requirement for dexamethasone for CNS disease; patients on a
                       stable dose of anticonvulsants are permitted

                    -  No neurosurgical resection or brain biopsy within 28 days prior to cycle 1,
                       day 1

               -  Patients with asymptomatic treated CNS metastases may be enrolled, provided all
                  the criteria listed above are met as well as the following:

                    -  Radiographic demonstration of improvement upon the completion of CNS
                       directed therapy and no evidence of interim progression between the
                       completion of CNS directed therapy and the screening radiographic study

                    -  No stereotactic radiation or whole-brain radiation within 28 days prior to
                       cycle 1, day 1

                    -  Screening CNS radiographic study >= 4 weeks from completion of radiotherapy
                       and >= 2 weeks from discontinuation of corticosteroids

          -  Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Patients requiring treatment with a receptor activator of nuclear factor kappa-B
             ligand (RANKL) inhibitor (e.g. denosumab) who cannot discontinue it before treatment
             with atezolizumab

          -  Known clinically significant liver disease, including active viral, alcoholic, or
             other hepatitis; cirrhosis; fatty liver; and inherited liver disease

               -  Patients with past or resolved hepatitis B infection (defined as having a
                  negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc
                  [antibody to hepatitis B core antigen] antibody test) are eligible

               -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if
                  polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)

          -  History or risk of autoimmune disease, including but not limited to systemic lupus
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
             associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's
             syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune
             thyroid disease, vasculitis, or glomerulonephritis

               -  Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
                  replacement hormone are eligible

               -  Patients with controlled type 1 diabetes mellitus on a stable insulin regimen, or
                  type 2 diabetes mellitus are eligible

               -  Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with
                  dermatologic manifestations only (e.g., patients with psoriatic arthritis would
                  be excluded) are permitted provided that they meet the following conditions:

                    -  Patients with psoriasis must have a baseline ophthalmologic exam to rule out
                       ocular manifestations

                    -  Rash must cover less than 10% of body surface area (BSA)

                    -  Disease is well controlled at baseline and only requiring low potency
                       topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%,
                       fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)

                    -  No acute exacerbations of underlying condition within the last 12 months
                       (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
                       retinoids, biologic agents, oral calcineurin inhibitors; high potency or
                       oral steroids)

          -  History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
             organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
             pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
             tomography (CT) scan; history of radiation pneumonitis in the radiation field
             (fibrosis) is permitted

          -  Patients with active tuberculosis (TB) are excluded

          -  Severe infections within 4 weeks prior to cycle 1, day 1, including but not limited to
             hospitalization for complications of infection, bacteremia, or severe pneumonia

          -  Signs or symptoms of infection within 2 weeks prior to cycle 1, day 1

          -  Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1;
             patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
             infection or chronic obstructive pulmonary disease) are eligible

          -  Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of
             need for a major surgical procedure during the course of the study

          -  Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or
             anticipation that such a live, attenuated vaccine will be required during the study
             and up to 5 months after the last dose of atezolizumab

               -  Influenza vaccination should be given during influenza season only (approximately
                  October to March); patients must not receive live, attenuated influenza vaccine
                  within 4 weeks prior to cycle 1, day 1 or at any time during the study

          -  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 positive for human immunodeficiency virus (HIV) are NOT excluded from this
             study, but HIV-positive patients must have:

               -  A stable regimen of highly active anti-retroviral therapy (HAART)

               -  No requirement for concurrent antibiotics or antifungal agents for the prevention
                  of opportunistic infections

               -  A cluster of differentiation (CD)4 count above 250 cells/mcL and an undetectable
                  HIV viral load on standard PCR-based tests

          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3 years, with the exception of those with a negligible risk of
             metastases or death, such as carcinoma in situ of the breast or cervix

          -  Severe, active co-morbidity defined as follows:

               -  Current (within 28 days of cycle 1, day 1) signs and/or symptoms of bowel
                  obstruction

               -  Patients who require parental hydration and/or nutrition

               -  Patients who require drainage gastrostomy tube

               -  Evidence of bleeding diathesis or clinically significant coagulopathy

               -  Serious, non-healing or dehiscing wound, active ulcer or untreated bone fracture

               -  History of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) within 1
                  month of study enrollment

          -  Significant cardiovascular or cerebrovascular disease including:

               -  Uncontrolled hypertension (systolic blood pressure [SBP] >= 150; diastolic blood
                  pressure [DBP] >= 90)

               -  History of myocardial infarction within 6 months

               -  Unstable angina

               -  New York Heart Association functional classification II, III or IV

               -  Baseline ejection fraction =< 50% as assessed by echocardiogram or multi-gated
                  acquisition (MUGA)

               -  Cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 6
                  months

               -  Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or
                  peripheral arterial thrombosis) within 6 months

          -  History of abdominal/pelvic or tracheoesophageal fistula or gastrointestinal
             perforation and/or abscess within 6 months prior to initiation of treatment

          -  Pregnant or lactating patients
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLT) of experimental regimens graded using Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0 (CTCAE version 5.0 will be used beginning April 1, 2018)
Time Frame:Up to 28 days
Safety Issue:
Description:DLT will be assessed.

Secondary Outcome Measures

Measure:Objective response rate (ORR) (partial or complete response) assessed by RECIST version (v.) 1.1 criteria (Phase II)
Time Frame:Up to 5 years
Safety Issue:
Description:Will be tabulated by treatment group, and 95% confidence intervals will be presented using Wilson's Score Method. Treatment arms will be compared using a likelihood ratio chi-square test.
Measure:Frequency and severity of adverse events assessed by CTCAE v. 4.0 (CTCAE version 5.0 will be used beginning April 1, 2018) (Phase II)
Time Frame:Up to 5 years
Safety Issue:
Description:The maximum grade of each adverse event (AE) by system organ class and Common Toxicity Criteria (CTC) 4.0 (CTCAE version 5.0 will be used beginning April 1, 2018) specific term will be tabulated for those individuals who at least initiate study treatment. The number and percent of individuals will be tabulated by the maximum grade of their AE.
Measure:Objective response rate (ORR) (partial or complete response) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 (Phase III)
Time Frame:Up to 5 years
Safety Issue:
Description:Will be tabulated by treatment group, and 95% confidence intervals will be presented using Wilson's Score Method. Treatment arms will be compared using a likelihood ratio chi-square test.
Measure:Progression free survival (PFS) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 criteria (Phase III)
Time Frame:From study enrollment to the investigator determined date of progression or death due to any cause, whichever occurs first, assessed up to 5 years
Safety Issue:
Description:Estimated using Kaplan-Meier estimates of the treatment-specific cumulative distribution.
Measure:Frequency and severity of adverse events assessed by CTCAE v. 4.0 (CTCAE version 5.0 will be used beginning April 1, 2018) (Phase III)
Time Frame:Up to 5 years
Safety Issue:
Description:The maximum grade of each AE by system organ class and CTC 4.0 (CTCAE version 5.0 will be used beginning April 1, 2018) specific term will be tabulated for those individuals who at least initiate study treatment. The number and percent of individuals will be tabulated by the maximum grade of their AE.
Measure:Disease-related symptoms as assessed by the National Comprehensive Cancer Network (NCCN)- Functional Assessment of Cancer Therapy (FACT) ovarian symptom index (NFOSI)-disease-related symptoms (DRS) (Phase II)
Time Frame:Up to 2 years
Safety Issue:
Description:A repeated measures model will be used to estimate and compare the mean DRS-physical (P) scores for the treatment groups. Model covariates will include the patients' randomly assigned study treatment, age at enrollment onto the study, initial performance status, pre-treatment DRS-P score, assessment time and treatment-by-time interaction. The primary analyses will include only those treatments selected at the end of the phase II study and all of the patients assigned to one of these treatments during either stage 2 of the safety lead-in, phase II or phase III component of the study regardless of their compliance with the study treatment or eligibility status, provided at least one baseline (pre-treatment) and one follow-up assessment is available.
Measure:Disease-related symptoms as assessed by the National Comprehensive Cancer Network (NCCN)- Functional Assessment of Cancer Therapy (FACT) ovarian symptom index (NFOSI)-disease-related symptoms (DRS) (Phase III)
Time Frame:Up to 2 years
Safety Issue:
Description:A repeated measures model will be used to estimate and compare the mean DRS-physical (P) scores for the treatment groups. Model covariates will include the patients' randomly assigned study treatment, age at enrollment onto the study, initial performance status, pre-treatment DRS-P score, assessment time and treatment-by-time interaction. The primary analyses will include only those treatments selected at the end of the phase II study and all of the patients assigned to one of these treatments during either stage 2 of the safety lead-in, phase II or phase III component of the study regardless of their compliance with the study treatment or eligibility status, provided at least one baseline (pre-treatment) and one follow-up assessment is available.
Measure:Patient reported outcomes (PRO) as measured by treatment side effects (TSE), function/well-being (FWB), fatigue and health status (Phase II)
Time Frame:Up to 2 years
Safety Issue:
Description:Each of the other general PRO scales will be analyzed with repeated measures models. Exploratory analyses will include an assessment of the model residuals in order to evaluate the adequacy of modeling assumptions. Additional descriptive analyses will assess whether the differences in mean scores between groups vary systematically with time in a linear or quadratic fashion.
Measure:Patient reported outcomes (PRO) as measured by treatment side effects (TSE), function/well-being (FWB), fatigue and health status (Phase III)
Time Frame:Up to 2 years
Safety Issue:
Description:Each of the other general PRO scales will be analyzed with repeated measures models. Exploratory analyses will include an assessment of the model residuals in order to evaluate the adequacy of modeling assumptions. Additional descriptive analyses will assess whether the differences in mean scores between groups vary systematically with time in a linear or quadratic fashion.
Measure:PD-L1 will be assessed in enrolled patients using immunohistochemistry on tumors embedded in paraffin
Time Frame:Up to 5 years
Safety Issue:
Description:The proportion of patients expressing PD-L1 in this patient population will be estimated. A proportional hazards model will be used to estimate the hazard of death for patients who express PD-L1 relative to those who do not express PL-D1 for each treatment group. The homogeneity of these estimated hazard ratios will then be assessed. Its association with the duration of PFS or OS will be determined.

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

April 27, 2018