Chemotherapy plus propranolol before surgery for advanced high-grade serous ovarian cancer

Chemotherapy Combined With Propranolol Hydrochloride as Neoadjuvant Therapy for Advanced High-grade Serous Ovarian Cancer: A Prospective, Multicenter, Phase II Clinical Study

The trial will try adding the beta-blocker propranolol to standard pre-surgery chemotherapy for people with advanced high-grade serous ovarian cancer to see if it improves tumor response and surgical outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Anhui Provincial Cancer Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation, prednisone, immunotherapy
• Locations: 1 site (Hefei, Anhui)
• Trial ID: NCT07125391 on ClinicalTrials.gov

What this trial studies

This phase II, interventional trial enrolls women with histologically confirmed high-grade serous ovarian cancer that is FIGO stage III or IV and not initially operable. Participants are assigned to one of two groups: neoadjuvant paclitaxel (or paclitaxel liposome) plus carboplatin for 3–4 cycles with or without propranolol started one week before chemotherapy (propranolol per protocol, 20 mg twice daily). After 3–4 cycles all patients undergo interval debulking surgery and tumor response is assessed before and after surgery, with safety monitored throughout. The study aims to test whether adding propranolol improves chemotherapy response, resectability, and short-term outcomes compared with chemotherapy alone.

Who should consider this trial

Good fit: Women aged 18–75 with measurable, histologically confirmed high-grade serous ovarian cancer at FIGO stage III or IV, ECOG 0–1, adequate organ function, and willingness to provide tissue samples are eligible.

Not a fit: Patients with early-stage disease, non-serous ovarian cancers, poor performance status (ECOG ≥2), significant cardiac or other organ dysfunction, or contraindications to beta-blockers are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, adding propranolol could improve tumor shrinkage before surgery and lead to better surgical outcomes and longer disease control.

How similar studies have performed: Preclinical studies and retrospective analyses in other cancers have suggested non-selective beta-blockers can enhance treatment response, but prospective data specifically in ovarian cancer are limited.

Eligibility criteria

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
  * Platelet (PLT) or 90 x 109 / L
  * Nmda aminotransferase (AST) 2.5 x ULN or less
  * Alanine aminotransferase (ALT) 2.5 x ULN or less
  * Total bilirubin (TBIL) 1.5 x ULN or less
  * Serum creatinine (SCr) 1.0 x ULN or less
  * Potential fertility women in the group of 7 days before the serum or urine HCG were negative (postmenopausal women considered must be at least 12 months of amenorrhea fertility; Pregnancy tests are not required for women with documented tubal ligation)
  * Potential fertility women are willing to take in the experiment of the medical contraception

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)
* Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive)
* Hepatitis b patients with known
* Activity of HCV infection subjects (HCV antibody positive and HCV - RNA levels higher than the detection limit)
* For the first time to give medicine before (1 cycle, day 1) vaccinated live vaccine within 30 days
* Pregnant or lactating women
* Any serious or uncontrolled systemic disease, such as

  * resting electrocardiogram (ecg) in rhythm, conduction, or have a significant and severe symptoms to appear on the form is hard to control the exceptions, such as complete left bundle branch block, Ⅱ degrees above heart block, ventricular arrhythmia or atrial fibrillation
  * Unstable angina and congestive heart failure, New York heart association (NYHA) classification of grade 2 or more chronic heart failure
  * Within 6 months before the selected treatment had any arterial thrombosis, embolism, or ischemia, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, etc.
  * First dose exist within 1 year before need to glucocorticoid treatment of infectious pneumonia history, or the current clinical activity interstitial lung disease; Active tuberculosis
  * There need systemic treatment of active or failure to control the infection
  * Clinical activity diverticulitis, abdominal abscess, gastrointestinal obstruction
  * Liver disease such as cirrhosis of the liver, decompensated liver disease, acute or chronic active hepatitis
  * Mental disorders and unable to cooperate with treatment
* Any medical history or evidence of illness, abnormal treatment or laboratory values, or other conditions that might interfere with the results of the trial or prevent full participation in the study, or any other potential risk that might be considered by the investigator to be inappropriate for enrollment.

Where this trial is running

Hefei, Anhui

• Anhui Cancer Hospitail — Hefei, Anhui, China (Recruiting)

Study contacts

• Study coordinator: Yao Xia, Doctor

Conditions Ovarian Cancer; NACT