NCT03394885

Atezolizumab With Neoadjuvant Chemotherapy for Patients With Newly-Diagnosed Advanced-Stage Ovarian Cancer

Atezolizumab in Combination With Neoadjuvant Chemotherapy and Interval Cytoreductive Surgery for Patients With Newly-Diagnosed Advanced-Stage Epithelial Ovarian Cancer

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Duke University · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main purpose of this study is to validate a safe dose of atezolizumab with dose-dense paclitaxel and carboplatin when utilized with neoadjuvant chemotherapy and interval cytoreductive surgery followed by maintenance atezolizumab in women with advanced ovarian cancer.

Detailed description

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.

Conditions

• Ovarian Cancer
• Ovarian Neoplasms

Interventions

Type	Name	Description
DRUG	Atezolizumab	1200mg IV q3weeks
DRUG	Carboplatin	5-6mg/ML IV q3 weeks
DRUG	Paclitaxel	70-80 mg/m2 IV q1 week
DRUG	Bevacizumab	15 mg/kg IV q3 weeks

Timeline

• Start date: 2018-06-19
• Primary completion: 2020-07-20
• Completion: 2020-07-20
• First posted: 2018-01-09
• Last updated: 2021-08-12
• Results posted: 2021-08-10

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study