First-line Maintenance Treatment With Fluzoparib Plus Bevacizumab in Advanced BRCA Wild Type Ovarian Cancer

NCT06063070 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: B2023-321-01
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multi-center Phase II study of fluzoparib combined with bevacizumab for maintenance therapy after first-line platinum-containing chemotherapy in patients with BRCA wild-type advanced ovarian cancer. The primary objective is to evaluate median progression free survival of fluzoparib plus bevacizumab.

Conditions

Ovarian Cancer; High Grade Serous Adenocarcinoma of Ovary; High Grade Endometrioid Ovarian Cancer; Primary Peritoneal Cancer; Fallopian-tube Cancer

Keywords

ovarian cancer; PARP inhibitors; Flzuoparib; Antiangiogenic agents; Bevacizumab; BRCA wild-type

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Time from the date of first study treatment administration to the date of first documented tumor progression or death due to any cause, whichever occurs first.

  from the first drug administration up to 2 years

Secondary Outcomes (7)

• Overall survival (OS)

  from the first drug administration up to 5 years

• Objective Response Rate (ORR)

  from the first drug administration up to 2 years

• Time to start of first subsequent therapy or death (TFST)

  from the first drug administration up to 5 years

• Time to start of second subsequent therapy or death (TSST)

  from the first drug administration up to 5 years

• Time to progression(TTP）by RECIST or CA-125

  from the first drug administration up to 5 years

Other Outcomes (1)

• Exploratory endpoint

  from the first drug administration up to 5 years

Study Arms (1)

Fluzoparib + Bevacizumab

EXPERIMENTAL

Fluzoparib capsule: oral administration, 3 capsules/dose (150 mg/ dose), twice a day, in the morning and evening, before/after meals can be taken orally, it is recommended to take orally within 0.5h after breakfast and dinner, continuous administration. Every 3 weeks is a treatment cycle. Bevacizumab injection: intravenous, 15 mg/kg, every 3 weeks for a treatment cycle until disease progression or intolerable toxicity, up to a total of 15 months.

Drug: Fluzoparib Capsules; Drug: Bevacizumab

Interventions

Fluzoparib Capsules DRUG

oral

Also known as: Poly (ADP-ribose) polymerase (PARP) inhibitor

Fluzoparib + Bevacizumab

Bevacizumab DRUG

Injectable solution

Also known as: Antiangiogenic agents

Fluzoparib + Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent and ability to comply with treatment and follow-up.
• Age ≥ 18 years (Calculated on the date the informed consent was signed).
• Pathologically confirmed high-grade serous (or medium-low differentiation) or high grade endometrioid (≥ grade II) ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer:
• \- Mixed tumors: high-grade serous or high grade endometrioid (≥ grade II) component must be \>50%.
• Patients with newly diagnosed, histologically confirmed, advanced (FIGO stage III or IV of the 2018 FIGO classification) ovarian, fallopian tube, or primary peritoneal cancer; and underwent tumor reduction surgery.
• Patients must have received prior to enrollment a minimum of 6 cycles and a maximum of 9 cycles of first line platinum-taxane chemotherapy. However, if platinum-based therapy must be discontinued early as a result of intolerable toxicity, patients must have received a minimum of 4 cycles of the platinum regimen:
• Preoperative neoadjuvant chemotherapy and postoperative chemotherapy counted as 1 chemotherapy treatment regimen.
• Patients must be prior to enrollment in complete response (CR) or partial response (PR) from their first line treatment, and use of the trial drug at least 3 weeks and no more than 9 weeks after their last dose of chemotherapy.
• At least 4 cycles of the platinum regimen treatment were completed.
• During or after platinum-containing chemotherapy, concurrent use of other investigational drugs and treatment other than endocrine therapy drugs are not permitted.
• Bevacizumab in combination with the first line platinum-taxane chemotherapy was allowed.
• At the end of the last platinum-containing regimen, the radiographic evaluation of the efficacy was CR or PR, CA125 was reduced to within the upper limit of normal (ULN) or ≥90% lower than pre-treatment levels during treatment, and CA125 was maintained at \<1x ULN or has not \>10% higher than previously observed for 7 days before the first trial of drug administration.
• If there is no evaluable lesion prior to chemotherapy, CA125 must remit to \<Upper Limit of Normal (ULN) during treatment and CA125 should be maintained at \<1x ULN for 7 days prior to the first trial dose.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Germline BRCA1/2 wild-type.

You may not qualify if:

• Previous (within 5 years) or concurrent with other uncured malignant tumors, except for cured skin basal cell carcinoma, cervical carcinoma in situ and breast cancer with no recurrence \>3 years after radical surgery;
• Patients with untreated central nervous system metastases:
• Patients with prior treatment (radiotherapy or surgery) for systemic, radical brain or meningeal metastases may be enrolled if imaging confirms that stabilization has been maintained for at least 1 month and systemic hormone therapy (dose \>10mg/day prednisone or other equivocal hormone) has been discontinued for more than 2 weeks and who have no clinical evidence can be included;
• Any previous treatment with PARP inhibitor, including, olaparib, niraparib, rucaparib, pamiparib, and fluzoparib;
• Inability to swallow tablets properly or gastrointestinal function, may interfere with drug absorption, according to the investigator.
• Recent (within 3 months) occurrence of intestinal obstruction, gastrointestinal perforation;
• Patients with clinically symptomatic carcinomatous ascites or pleural effusion who need puncture or drainage or who have received drainage of ascites or pleural effusion within 2 months prior to the first trial of drug administration.
• Patients with clinically significant cardiovascular disease that are not well controlled, such as (1) New York Heart Association (NYHA) ≥ grade 2 congestive heart failure (CHF) (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention (5) QTc \> 470ms;
• Patients with abnormal coagulation (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 seconds), bleeding tendency, or who are receiving thrombolytic or anticoagulant therapy are permitted to receive low-dose low molecular heparin or oral aspirin for prophylactic anticoagulation during the trial;
• Patients who have experienced clinically significant bleeding symptoms or have a definite bleeding tendency within 3 months prior to the first dose, such as peptic bleeding, bleeding gastric ulcer, or suffering from vasculitis, etc., may be retested if the fecal occult blood is positive at the baseline period, and if it is still positive after the retesting, combined with the clinical judgment, and if necessary, gastroscopy will be carried out;
• Accompanied by active ulcers, unhealed wounds or with fractures;
• Patients who suffering from hypertension which cannot be well controlled by antihypertensive medication (systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥ 90mmHg);
• Any bleeding event with a severity rating of 2 or more on the CTCAE 5.0 within 4 weeks prior to the first dose;
• Patients has an active infection or an unexplained fever \>38.5 degrees during the screening period, prior to the first dose;
• Patients who has a congenital or acquired immune deficiency (e.g., HIV-infected), or active hepatitis (Hepatitis B reference: HBsAg-positive, HBV DNA ≥500 IU/ml; Hepatitis C reference: HCV antibody-positive, HCV viral copy number \> upper limit of normal);

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Cetntre

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

fluzoparib; Poly A; Adenosine Diphosphate Ribose; Bevacizumab; Angiogenesis Inhibitors

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Polyribonucleotides; Polynucleotides; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Adenosine Diphosphate Sugars; Adenosine Diphosphate; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleoside Diphosphate Sugars; Glycosides; Carbohydrates; Ribonucleotides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Growth Inhibitors; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Chunyan Lan

CONTACT

18928806306; lanchy@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: Drug: fluzoparib plus Bevacizumab

Study Record Dates

• First Submitted: September 19, 2023
• First Posted: October 2, 2023
• Study Start: October 18, 2023
• Primary Completion: January 31, 2025
• Study Completion (Estimated): October 30, 2027
• Last Updated: October 2, 2023

Record last verified: 2023-09

Locations

CN (1)