Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
A Randomized Phase 2 Trial of Atezolizumab (MPDL3280A), SGI-110 and CDX-1401 Vaccine in Recurrent Ovarian Cancer
4 other identifiers
interventional
12
1 country
17
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2017
Typical duration for phase_1
17 active sites
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
First Submitted
Initial submission to the registry
June 30, 2017
CompletedFirst Posted
Study publicly available on registry
July 2, 2017
CompletedStudy Start
First participant enrolled
November 8, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 10, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
November 10, 2020
CompletedMarch 13, 2025
March 1, 2025
3 years
June 30, 2017
March 12, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events (AE) (Phase I)
Will be listed individually per patient according to Common Terminology Criteria for Adverse Events version 5.0, and the number of patients experiencing each AE will be summarized using descriptive statistics.
Up to 30 days after last dose
Progression free survival (PFS) (Phase IIb)
Assessed using standard imaging response (Response Evaluation Criteria in Solid Tumors \[RECIST\]) criteria. Will be carried forth using a Cox proportional hazards model with a factor for treatment with a stratification factor for disease subtype relative to the determining the form of the likelihood function. The global test statistic will combine from the one-sided tests using Fisher's method for combining p-values. Will also examine potential differential effect of NY-ESO-1 expression on PFS. The analysis of expression levels between the three groups will be carried out using analysis-of-variance methods on either the raw values or log transformed values.
Up to 1 year
Secondary Outcomes (9)
Anti-tumor activity (Phase I)
Up to 1 year
Overall survival (OS) (Phase IIb)
Up to 1 year
Objective response rate (Phase IIb)
Up to 1 year
Clinical benefit rate (Phase IIb)
Up to 1 year
CA-125 reduction (Phase IIb)
Up to 1 year
- +4 more secondary outcomes
Other Outcomes (7)
NY-ESO-1-specific immune responses
Up to 1 year
PDL1 expression in tumor tissue
Up to 1 year
AIM gene signatures
Up to 1 year
- +4 more other outcomes
Study Arms (3)
Cohort I (atezolizumab)
EXPERIMENTALPatients 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.
Cohort II (guadecitabine, atezolizumab)
EXPERIMENTALPatients 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.
Cohort III (guadecitabine, atezolizumab, CDX-1401 vaccine)
EXPERIMENTALPatients 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.
Interventions
Given IV
Given SC
Given SC
Correlative studies
Given SC
Eligibility Criteria
You may qualify if:
- 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)
- +6 more criteria
You may not qualify if:
- Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
- Patients who have had chemotherapy or radiotherapy including complementary and alternative medicine treatments (CAMs) within 4 weeks prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier
- Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
- Minimum of 12 weeks from the first dose of anti-CTLA-4 and \> 6 weeks from the last dose
- No history of severe immune-related adverse effects from anti-CTLA-4 (NCI CTCAE grade 3 and 4)
- 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) 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; use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
- Concomitant systemic treatment with chronic use of anti-histamine or non-steroidal anti-inflammatory drugs and other platelet inhibitory agents and patients on oral anticoagulant (e.g. warfarin); exception: patients on therapeutic anticoagulation therapy such as low-molecular-weight heparin or warfarin at a stable dose level are allowed on study
- Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- +34 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
Banner University Medical Center - Tucson
Tucson, Arizona, 85719, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, 60451, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, 60462, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
Nebraska Medicine-Village Pointe
Omaha, Nebraska, 68118, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kunle Odunsi
Roswell Park Cancer Institute EDDOP
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 30, 2017
First Posted
July 2, 2017
Study Start
November 8, 2017
Primary Completion
November 10, 2020
Study Completion
November 10, 2020
Last Updated
March 13, 2025
Record last verified: 2025-03