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Active Clinical Trials

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

NCT:
02839707
West Penn Hospital
West Penn Hospital

Sponsor: 
National Cancer Institute (NCI)
Contact: 

For more information, please contact Erin Baldauf by telephone at 412-578-4517 or by email at Erin.Baldauf@ahn.org or Hannah Makarevich by telephone at 412-578-4216 or by email at Hannah.Makarevich@AHN.ORG.

A Randomized, Phase II/III Study of Pegylated Lipsomal Doxorubicin and CTEP-Supplied Atezolizumab versus Pegylated Liposomal Doxorubicin/Bevacizumab and CTEP-Supplied Atezolizumab versus Pegylated Liposomal Doxorubicin/Bevacizumab in Platinum Resistant Ovarian Cancer

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.

Ages Eligible for Study:  18 Years and older   (Adult, Senior)

Sexes Eligible for Study:  Female

Accepts Healthy Volunteers:  No

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

Absolute neutrophil count (ANC) >= 1,500/mcl

Platelets >= 100,000/mcl

Hemoglobin (Hgb) >= 8 g/dl

Creatinine =< 1.5 x institutional upper limit of normal (ULN)

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 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm

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

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