A Randomized Phase 2 Trial of Atezolizumab (MPDL3280A), SGI-110 and CDX-1401 Vaccine in Recurrent Ovarian Cancer

Who is this study for? Patients with ovarian, fallopian tube, or primary peritoneal cancer
Status: Active_not_recruiting
Location: See all (17) locations...
Intervention Type: Drug, Biological, Other
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY

This randomized phase I/IIb trial studies side effects and best dose of atezolizumab when given together with guadecitabine and CDX-1401 vaccine and to see how well they work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. CDX-1401 vaccine may enhance the expression of the genes encoding tumor antigens on the surface of tumor cells and enhance the activity of tumor-killing T cells against those tumor cells. Vaccines made from monoclonal antibodies combined with tumor cells may help the body build an effective immune response to kill tumor cells. Giving atezolizumab, guadecitabine, and CDX-1401 vaccine may work better than CDX-1401 alone in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Eligibility
Participation Requirements
Sex: Female
Minimum Age: 18
Healthy Volunteers: f
View:

• Women with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with platinum-resistant disease (defined as having relapsed within 6 months of last platinum-containing regimen because we would like to include both primary and secondary resistance); patients are allowed to have had more than 2 prior cytotoxic treatment regimens; all patients should have received standard of care agents, which confer clinical benefit

• Presence of biopsiable disease and patient able to undergo pre-treatment and on-treatment biopsy

• Tissue available from primary and/or recurrent disease to evaluate tumor expression of NY-ESO-1 or PDL1 by immunohistochemistry (IHC) and/or reverse transcriptase-polymerase chain reaction (RT-PCR), and for measurement of DNA methylation

• No requirement for tumor expression of NY-ESO-1

• Life expectancy \> 6 months as assessed by study physician

• Because no dosing or adverse event data are currently available on the use of atezolizumab in combination with SGI-110 and CDX-1401 in patients \< 18 years of age, children are excluded from this study, but may be eligible for future pediatric trials

• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2

• Have been informed of other treatment options

• Have measurable disease outside of biopsy site present per immune related (ir)RECIST criteria; (Rationale: Biopsy may also induce an inflammatory response and bias outcome measurements)

• Patients may have received previous NY ESO 1 vaccine therapy; patients who received bevacizumab or other experimental therapies are eligible for enrollment provided they have discontinued therapy (at least 4 weeks) prior to randomization and recovered from toxicities to less than grade 2

• Leukocytes \>= 2,500/mcL

• Absolute neutrophil count \>= 1,500/mcL

• Platelets \>= 100,000/mcL

• Hemoglobin \>= 10 g/dL

• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled)

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x ULN (AST and/or ALT =\< 3 x ULN for patients with liver involvement)

• Alkaline phosphatase =\< 2 x ULN (=\< 5 x ULN for patients with documented liver involvement or bone metastases)

• Creatinine clearance \>= 30 mL/min/1.73 m\^2 by Cockcroft-Gault

• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =\< 1.5 x ULN

• Administration of the drugs used in this study may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential 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

• Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Locations
United States
Arizona
Banner University Medical Center - Tucson
Tucson
University of Arizona Cancer Center-North Campus
Tucson
California
City of Hope Comprehensive Cancer Center
Duarte
University of California Davis Comprehensive Cancer Center
Sacramento
Illinois
University of Chicago Comprehensive Cancer Center
Chicago
UC Comprehensive Cancer Center at Silver Cross
New Lenox
University of Chicago Medicine-Orland Park
Orland Park
Kansas
University of Kansas Clinical Research Center
Fairway
Nebraska
Nebraska Medicine-Village Pointe
Omaha
University of Nebraska Medical Center
Omaha
New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick
New York
Roswell Park Cancer Institute
Buffalo
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York
Memorial Sloan Kettering Cancer Center
New York
Ohio
Ohio State University Comprehensive Cancer Center
Columbus
Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh
Utah
Huntsman Cancer Institute/University of Utah
Salt Lake City
Time Frame
Start Date: 2017-11-08
Completion Date: 2025-03-31
Participants
Target number of participants: 75
Treatments
Experimental: Cohort I (atezolizumab)
Patients receive atezolizumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Experimental: Cohort II (guadecitabine, atezolizumab)
Patients receive guadecitabine SC on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive atezolizumab IV over 30-60 minutes on days 8 and 22. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Experimental: Cohort III (guadecitabine, atezolizumab, CDX-1401 vaccine)
Patients receive guadecitabine and atezolizumab as in Cohort II. Patients also receive CDX-1401 vaccine IV on day 15 and poly ICLC SC on days 15-16. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Related Therapeutic Areas
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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