Atezolizumab With Neoadjuvant Chemotherapy for Patients With Newly-Diagnosed Advanced-Stage Ovarian Cancer (AdORN)
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|ClinicalTrials.gov Identifier: NCT03394885|
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : August 20, 2019
|Condition or disease||Intervention/treatment||Phase|
|Ovarian Cancer Ovarian Neoplasms||Drug: Atezolizumab Drug: Carboplatin Drug: Paclitaxel Drug: Bevacizumab||Phase 1 Phase 2|
This is a Phase IB non-randomized, single-arm, open-label study of atezolizumab in combination with primary NACT-ICS in patients with advanced-stage epithelial ovarian cancer. The target population is women with previously untreated epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) with advanced stage (FIGO III-IV) disease suitable for NACT and ICS. The following regimen will be administered every 3 weeks for 3 cycles prior to ICS, then for 3 cycles following ICS:
- Carboplatin AUC = 5 or 6 IV, D1 of each cycle
- Paclitaxel 70 to 80mg/m2 IV, over one hour, on D1, 8, 15 of each cycle
- Atezolizumab 1200mg IV D1 of each cycle of chemotherapy and will be continued as maintenance therapy every 3 weeks until there is a lack of clinical benefit, unacceptable toxicity, or a total duration of 18 months.
- Bevacizumab (15 mg/kg IV every 3 weeks) may be added at cycle 5 of chemotherapy as per FDA approval. Those who opt for bevacizumab will receive chemotherapy, atezolizumab, and bevacizumab for cycles 5 and 6 followed by atezolizumab and bevacizumab maintenance. Maintenance bevacizumab will be given for a total duration of 16 cycles. Patients who have completed chemotherapy may opt for bevacizumab in the maintenance setting only if the amendment to add bevacizumab was not approved before after they started maintenance therapy.
- Upon completion of concurrent chemotherapy and atezolizumab therapy, patients will commence maintenance treatment with atezolizumab + bevacizumab for a total of up 16 cycles of maintenance therapy (22 total cycles of atezolizumab, and 18 total cycles of bevacizumab).
Each cycle is 21 days in duration and will be administered in the outpatient setting. Limited individualized flexibility in dose assignment (as noted) is permitted per physician discretion in regards to advanced-stage disease, nutritional status, ascites, non-physiologic creatinine measurements, and other comorbidities.
Three cycles of NACT with atezolizumab will be administered every 3 weeks prior to ICS (occurring between cycles 3 and 4) followed by 3 additional cycles (cycles 4-6) of chemotherapy with atezolizumab. Surgery must be performed after the third course of chemotherapy as soon as nadir counts permit, but preferably within six weeks after the completion of the third chemotherapy cycle. Fourth cycle of chemotherapy is to be administered as soon as possible, but preferably no more than six weeks after ICS.
Safety monitoring, including assessment for irAEs, will occur at each cycle and for 90 days after the last administration of atezolizumab or until start of next anti-cancer regimen, whichever occurs first. Image assessment by CT scan or MRI will be performed at baseline, prior to ICS to assess response, after completion of 6 cycles of chemotherapy with atezolizumab to assess response at end of chemotherapy treatment, and as clinically indicated during the maintenance phase and after completion of study treatment to assess PFS. Disease progression/recurrence will be defined per RECIST criteria and will not include isolated asymptomatic progression on the basis of CA125 levels. Immune function analysis will be performed on blood and tumor samples obtained at two time points: 1. confirmatory biopsy prior to start of therapy and 2. ICS.
It is estimated that 40 patients will be enrolled at an accrual rate of 3-5 patients/month and followed for a median of 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Atezolizumab in Combination With Neoadjuvant Chemotherapy and Interval Cytoreductive Surgery for Patients With Newly-Diagnosed Advanced-Stage Epithelial Ovarian Cancer|
|Actual Study Start Date :||June 19, 2018|
|Estimated Primary Completion Date :||January 2021|
|Estimated Study Completion Date :||June 2022|
Experimental: Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)
1200mg IV q3weeks
Other Name: Tecentriq
5-6mg/ML IV q3 weeks
Other Name: Paraplatin
70-80 mg/m2 IV q1 week
Other Name: Taxol
15 mg/kg IV q3 weeks
Other Name: Avastin
- Safety: Incidence of post chemotherapy surgical debulking [ Time Frame: 9 weeks ]The ability of subjects to undergo interval cytoreductive surgery will be utilized as a measure of safety regarding the initial dosing of atezolizumab
- Safety: Incidence of treatment emergent adverse events [ Time Frame: 18 months ]The number of adverse events experienced while receiving study drugs will be utilized to assess safety of atezolizumab
- Safety: Dose intensity [ Time Frame: 18 months ]Percentage of planned dose received at each cycle will be utilized as a measure of safety and tolerability for each subject.
- Safety: Incidence of dose modifications [ Time Frame: 18 months ]The number of dose modifications will be utilized as a measure of safety and tolerability for each subject
- Objective Response Rate [ Time Frame: 18 months ]RECIST criteria will be utilized for subjects over the course of the study to measure their response to study drugs
- Pathologic complete remission rate [ Time Frame: 9 weeks ]At interval cytoreduction pathologic complete remission rate will be measured using RECIST and immune-related response criteria.
- Progression Free Survival [ Time Frame: 18 months ]All patients will be evaluated for progression free survival from the date of first treatment to the date of first observation of progressive disease or death due to any cause or will be stopped at date of last follow-up for those still alive without disease progression.
- Overall survival [ Time Frame: 18 months ]All patients will be evaluated for overall survival from the date of first treatment on protocol to the date of death due to any cause and will be stopped at date of last follow-up for those still alive.
- Translational: PD-L1 Expression [ Time Frame: 18 months ]Analyzing changes in PD-L1 expression measured based on: immunohistochemistry after treatment with atezolizumab, association with BRCA mutation status, tumor mutation profile (next generation sequencing), and progression free survival.
- Translational: Tumor infiltrating lymphocytes [ Time Frame: 18 months ]Analyzing changes in tumor infiltrating lymphocytes expression based on: immunohistochemistry after treatment with atezolizumab, association with BRCA mutation status, tumor mutation profile (next generation sequencing) and progression free survival.
- Translational: Immune checkpoint receptors [ Time Frame: 18 months ]Analyzing changes in immune checkpoint receptor expression based on: flow cytometry after treatment with atezolizumab, association with BRCA mutation status, tumor mutation profile (next generation sequencing) and progression free survival.
- Translational: Cytokine expression [ Time Frame: 18 months ]Analyzing changes in cytokine expression based on: ELISA (enzyme-linked immunosorbent assay) after treatment with atezolizumab, association with BRCA mutation status, tumor mutation profile (next generation sequencing) and progression free survival.
- Translational: Gene expression profiles [ Time Frame: 18 months ]Analyzing changes in gene expression profiles based on: RNA sequencing after treatment with atezolizumab, association with BRCA mutation status, tumor mutation profile (next generation sequencing) and progression free survival.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03394885
|Contact: William S Andrews, BSNfirstname.lastname@example.org|
|Contact: Kara Hagler, RN, BSNemail@example.com|
|United States, North Carolina|
|Duke Cancer Institute||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: William S Andrews, BSN 919-684-3780 firstname.lastname@example.org|
|Contact: Kara Hagler, RN, BSN 919-684-3780 email@example.com|
|Principal Investigator: Angeles A Secord, MD|
|United States, Virginia|
|University of Virginia||Not yet recruiting|
|Charlottesville, Virginia, United States, 22908|
|Contact: Rachel Lacey 434-243-0126 firstname.lastname@example.org|
|Principal Investigator: Kari Ring, MD|
|Principal Investigator:||Angeles A Secord, MD||Duke University|