Chemotherapy Combined With Propranolol Hydrochloride as Neoadjuvant Therapy for Advanced High-grade Serous Ovarian Cancer: A Prospective, Multicenter, Phase II Clinical Study
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Bai-Rong Xia
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- CRS
Overview
Brief Summary
Ovarian Cancer (OC) is one of the most common gynecological malignant tumors. In recent years, the incidence of ovarian cancer in China has been on the rise, but its mortality ranks the first among gynecological tumors. Cytoreductive Surgery (CRS) combined with chemotherapy is the standard treatment for patients with advanced ovarian cancer. However, most of the ovarian cancer is stage Ⅲ and above, and there may be a certain degree of organ metastasis. Preclinical studies have found that the stress of melanoma block beta adrenergic signals in mice, which USES beta blockers, checkpoint will enhance resistance to PD - 1 the activity of the inhibitor, to improve the treatment of mice on the immune response. Non-selective β-blockers can also improve the efficacy of melanoma immunotherapy. Retrospective studies have shown that incidental use of β-blockers in combination with antiangiogenic agents, chemotherapy, and immune therapy can prolong DFS, PFS, and OS in cancer patients. A large, multicenter retrospective study found that ovarian cancer patients who took nonselective β-blockers for hypertension had better survival than those who did not. In conclusion, this study aims to explore new auxiliary chemotherapy combined propranolol treatment of high efficacy and safety of ovarian cancer, provide more evidence-based basis for clinic.
Detailed Description
The study included patients with inoperable stage III or IV ovarian cancer who were initially treated in FIGO stage III or IV. "A phase II trial to explore the efficacy and safety of neoadjuvant chemotherapy plus propranolol in patients with histologically confirmed high-grade serous ovarian cancer." Na row standard subjects were divided into 2 groups: Queue A accept propranolol hydrochloride (20 mg, BID, QD), paclitaxel/paclitaxel liposome (135-175 mg/m2, d1, Q3W) and carboplatin (AUC = 4-5, d1, Q3W), neoadjuvant therapy cycle, A total of 3-4 Subsequently, interval debulking surgery (IDS) was performed. Propranolol hydrochloride was taken one week before neoadjuvant therapy. Queue B receive paclitaxel/paclitaxel liposome (135-175 mg/m2, d1, Q3W) and carboplatin (AUC = 4-5, d1, Q3W), neoadjuvant therapy cycle, a total of 3-4 line then intermittent tumor cells to destroy the loss (interval debulking surgery, IDS); Patients will accept the tumor assessment before the surgery, postoperative by researchers according to aid in the treatment of ovarian cancer guidelines take corresponding.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent was obtained before any trial-related procedures were performed.
- •Women, 18 to 75 years old;
- •FIGO stage for stage III or IV, including not surgery in patients with stage III or IV beginning for ovarian cancer; Histopathology confirmed high-grade serous ovarian cancer.
- •According to the response evaluation criteria in 1.1 (RECIST1.1) definition, patients must have a measurable lesions
- •Agreed to provide the participants formalin fixed and tumor tissue specimens or fresh biopsy tissue tumor lesions markers detection
- •ECOG score 0-1 points
- •Expected survival time 6 months or more
- •Enough organ function, without severe hematopoietic dysfunction and heart, lung, liver, kidney dysfunction, and immune deficiency, participants need to satisfy the following laboratory indicators
- •hemoglobin (HGB) 90 g/L or higher
- •Neutrophils (NEUT) acuity 1.5 x 109 / L or white blood cell count (WBC) or 3 x 109 / L
Exclusion Criteria
- •Malignant diseases other than ovarian cancer (excluding radical skin basal cell carcinoma, skin squamous cell carcinoma, and/or radical resection in situ carcinoma) diagnosed within 5 years before the first dose
- •Current are participating in clinical research and treatment of intrusive, or within 4 weeks before the first dose received study used drugs or other treatments
- •Always received pelvic radiotherapy and systemic chemotherapy for ovarian cancer, tumor targeting therapy, immune therapy
- •Need treatment of symptomatic or non-control brain metastasis at the same time, including but not limited to, surgery, radiation and/or corticosteroids, or with the clinical manifestations of spinal cord compression
- •Current use of oral or intravenous beta blockers (atenolol, peso parlour, carvedilol and labetalol, metoprolol, than the parlour, his law such as beta blockers) cannot safely use of propranolol
- •Patients with contraindications to β-blockers were excluded according to the contraindications in the propranolol package insert.
- •Patients were receiving systemic glucocorticoids (excluding topical glucocorticoids by nasal spray, inhalation, or other route) or any other form of immunosuppressive therapy within 7 days before the first study dose; Note: allows the use of physiological doses of corticosteroids (10 mg/day or less prednisone or equivalent drugs)
- •Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation
- •Patients who were allergic to the active ingredient or excipients of propranolol hydrochloride in this study
- •Have not fully recovered from any intervention-related toxicity and/or complications before starting treatment (i.e., ≤ grade 1 or baseline, excluding fatigue or alopecia)
Arms & Interventions
Control group
Received paclitaxel/paclitaxel liposome (135 - 175mg/m2, d1, Q3W), carboplatin (AUC=4-5, d1, Q3W), neoadjuvant therapy for 3 - 4 cycles, followed by interval debulking surgery (IDS)
Intervention: Cohort A (Drug)
Outcomes
Primary Outcomes
CRS
Time Frame: 3-month
Chemotherapy Response Scoring：Pathological assessment was conducted on the retinal tissue removed during the surgery
Secondary Outcomes
- R0 resection rate(3-month)
- Overall Response Rate (ORR) After Neoadjuvant treatment(3-month)
- Pathological complete remission rate(3-month)
- 12-month disease-free survival rate(12 months)
- 12-month survival rate(12 months)
Investigators
Bai-Rong Xia
Chairman of Department of Gynaecology Surgery
Anhui Provincial Cancer Hospital