A Phase II Study of Neoadjuvant Chemotherapy Plus Durvalumab (MEDI4736) and Tremelimumab in Advanced-stage Ovarian Cancer (TRU-D)
Overview
- Phase
- Phase 2
- Intervention
- Neoadjuvant chemotherapy+Durvalumab+Tremelimumab
- Conditions
- Ovarian Cancer Stage IIIC
- Sponsor
- Yonsei University
- Enrollment
- 24
- Locations
- 4
- Primary Endpoint
- Progression-free survival(PFS)
- Last Updated
- 5 years ago
Overview
Brief Summary
The primary objective of this trial is to evaluate the synergistic effects of durvalumab and tremelimumab plus chemotherapy in advanced-stage ovarian cancer.
Ovarian cancer is the deadliest gynecologic cancer. The current standard therapy is surgical cytoreduction followed by taxane-platinum combination chemotherapy. However, most patients with advanced-stage ovarian cancer will experience a relapse of disease. Therefore, there is an urgent need to improve outcomes of patients with this aggressive cancer.
Research hypothesis: Adding durvalumab and tremelimumab to current neoadjuvant chemotherapy (front-line therapy) in advanced-stage ovarian cancer can increase response rate and improve patient's outcome such as progression-free survival and overall survival with minimal effects on safety.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed adenocarcinoma of ovary, fallopian tube, primary peritoneum
- •Clinical stage IIIC/IV
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act in the US, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- •Female aged 20 years older at the time of acquisition of informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 \~ 1
- •Must have life expectancy of at least 16 weeks
- •Body weight \>30kg
- •Adequate normal organ and marrow function as defined below:
- •Haemoglobin ≥9.0 g/dL
- •Absolute neutrophil count (ANC) ≥1.5 x 109/L
Exclusion Criteria
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- •Participation in another clinical study with an investigational product during the last 60 days
- •Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- •Any previous treatment with anti-PD-1, PD-L1, CTLA-4 (including durvalumab and tremelimumab)
- •Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
- •Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
- •Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
- •Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. \<\<amend as required based on any combination studies with other anticancer agents\>\>
- •Major surgical procedure (except diagnostic laparoscopy) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
- •History of allogenic organ transplantation.
Arms & Interventions
Neoadjuvant chemotherapy+Durvalumab+Tremelimumab
1. Neoadjuvant treatment: Standard chemotherapy + Durvalumab + Tremelimumab Durvalumab : 1500mg q3 weeks (total 3 dosing) Tremelimumab : 75mg q 3 weeks (total 3 dosing) Chemotherapy regimen: Paclitaxel 175 mg/m2 , Carboplatin AUC 5-6 q3 weeks (total 3 dosing) 2. Interval debulking surgery 3. Adjuvant treatment: Standard chemotherapy + Durvalumab Durvalumab; 1120mg q3 weeks (total 12 dosing) Chemotherapy regimen: Paclitaxel 175mg/m2, carboplatin AUC 5-6 q 3weeks (total3 dosing)
Intervention: Neoadjuvant chemotherapy+Durvalumab+Tremelimumab
Outcomes
Primary Outcomes
Progression-free survival(PFS)
Time Frame: 12 months
12-months progression-free survival rate will be estimated, and 95% confidence intervals will be calculated.
Secondary Outcomes
- Proportion of patients with grade 3 or more treatment-related adverse events(except hematologic toxicity) graded by CTCAE v5 in neoadjuvant chemotherapy(9 weeks)
- Response rate(9 weeks)
- The rate of chemotherapy response score 3(9 weeks)
- Immune-related response(9 weeks)
- Overall survival(up to 5 years)
- Response rate by PERCIST(9 weeks)
- R0 rate(at interval debulking surgery after 9 weeks)