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An Exploratory Study on the Use of Ipalotinib (Tislelizumab) Combined With Sunitinib and Olaparib for Neoadjuvant Therapy in HRD-positive Advanced Ovarian Cancer

2026年6月19日 更新者:Bai-Rong Xia
The R0 resection rate in neoadjuvant chemotherapy for advanced ovarian cancer remains below 50%, indicating unmet clinical needs. Tyrosine kinase inhibitors (TKIs) can induce immune microenvironment remodeling and exhibit synergistic effects with immune checkpoint inhibitors. To further evaluate the efficacy and safety of epalolide combined with torvolumab plus sunitinib and olaparib as neoadjuvant therapy in HRD-positive untreated patients with advanced ovarian cancer, a prospective, multicenter, single-arm exploratory study is proposed. This study will enroll 35 untreated HRD-positive advanced ovarian cancer patients who will receive neoadjuvant treatment with epalolide plus torvolumab combined with sunitinib and olaparib. Patients achieving CR/PR/SD after neoadjuvant therapy will undergo intermediate tumor cytoreductive surgery, followed by 6 cycles of adjuvant chemotherapy and 1 year of maintenance therapy with the etoricoxib-drug combination antibody regimen. The primary endpoint is R0 resection rate, aiming to provide valuable insights into neoadjuvant treatment strategies for advanced ovarian cancer patients.

調査の概要

状態

募集

条件

詳細な説明

For patients with advanced ovarian cancer, tumor debulking surgery is a crucial component of treatment. However, due to poor prognosis and high recurrence rates in advanced cases, treatment poses significant challenges. The primary principle of surgical management for advanced ovarian cancer is to achieve maximal tumor resection. The core objective of surgery is to remove all macroscopically visible tumor tissue to minimize postoperative residual disease. Nevertheless, given the complexity of advanced ovarian cancer and individual patient variability, not all patients are suitable candidates for initial tumor debulking surgery. Neoadjuvant chemotherapy combined with intermediate tumor debulking surgery serves as a therapeutic option for patients who cannot achieve satisfactory tumor reduction or are unable to tolerate surgery, and this approach is currently widely employed in clinical practice.

The traditional neoadjuvant treatment regimen for ovarian cancer involves the platinum-paclitaxel dual-drug combination. However, the complete resection rate with pure neoadjuvant chemotherapy remains below 50%, and approximately half of patients fail to achieve complete tumor removal. These patients face the risk of residual tumors postoperatively, which increases the likelihood of disease recurrence, highlighting a significant unmet clinical need. Improving neoadjuvant treatment strategies for ovarian cancer has become a current research focus. Existing studies demonstrate that combining immune checkpoint inhibitors with neoadjuvant chemotherapy can enhance the pathological complete response (pCR) rate in advanced ovarian cancer patients and induce durable clinical responses, suggesting this approach as a promising therapeutic option; however, further validation is required, and the optimal immunotherapy combination strategy requires further exploration.

Apatinib-tolilimumab (hereinafter referred to as the Ato combination antibody) is the world's first dual-functional combination antibody targeting both PD-1 and CTLA-4, capable of simultaneously inhibiting PD-1-and CTLA-4-mediated signaling pathways to exert synergistic antitumor effects with excellent tolerability. In Phase I clinical studies, the Ato combination antibody demonstrated superior safety and tolerability. Among 518 patients with advanced cancer who had failed conventional treatments, only 8.1% experienced grade 3 or higher immune-related adverse events, highlighting its significant safety advantages. In patients with recurrent or metastatic cervical cancer, the pivotal Phase II registration study of the Ato combination antibody achieved remarkable results: an overall response rate (ORR) of 33.8% in second-line systemic therapy and a median progression-free survival (PFS) of 5.4 months. Based on these data, the Ato combination antibody was approved for marketing in China on September 30,2024, indicated for the treatment of recurrent or metastatic cervical cancer patients who had previously failed platinum-based chemotherapy.

PARP inhibitors and antiangiogenic agents can disrupt tumor growth through distinct mechanisms, with their synergistic effects mutually enhancing each other to achieve a 1+1>2 outcome. Multitarget tyrosine kinase inhibitors (TKIs) can induce remodeling of the immune microenvironment and activate the tumor immune response, not only significantly increasing T-cell infiltration into tumors but also upregulating the expression of the immune checkpoint CTLA-4, ultimately enabling tumor cells to evade T-cell attack through immune evasion. CTLA-4 blockade enhances T-cell antitumor activity and effectively reverses the inhibitory immune microenvironment. Sunitinib is a TKI currently used as standard therapy for clear cell renal cell carcinoma (ccRCC) and gastrointestinal stromal tumors (GIST). Studies suggest that sunitinib may play a role in tumor immune monitoring and participate in PD-L1 regulation.

In patients with previously untreated advanced ovarian cancer, the use of neoadjuvant therapy combining TKIs and PARP inhibitors with epalolide and torvocizumab has a solid scientific basis and warrants further investigation. This study innovatively employed sunitinib combined with olaparib for one cycle to induce an immune microenvironment, followed by addition of an immune checkpoint inhibitor, demonstrating synergistic effects. To further evaluate the efficacy and safety of sunitinib and olaparib combined with epalolide and torvocizumab in neoadjuvant treatment for these patients, a prospective, multicenter, single-arm exploratory study is planned to provide valuable insights for developing neoadjuvant treatment regimens for advanced ovarian cancer.

研究の種類

介入

入学 (推定)

35

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

      • Hefei、中国
        • 募集
        • Anhui Cancer Hospital
        • コンタクト:
          • bairong xia, MD

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

Inclusion Criteria:

  1. Female participants aged ≥18 years and ≤75 years at enrollment;
  2. Histologically or cytologically confirmed diagnosis of epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma, with histopathological confirmation of high-grade serous carcinoma or endometrioid carcinoma, and FIGO stage (2014 edition) III-IV;
  3. Meeting the neoadjuvant indications for ovarian cancer (preoperative evaluation by a gynecologic oncologist indicates low likelihood of achieving R0 resection with initial debulking surgery, or the patient's physical condition is unsuitable for immediate surgery due to poor tolerance to PDS);
  4. Positive HRD testing result;
  5. Presence of at least one measurable lesion meeting RECIST 1.1 criteria;
  6. Expected survival time ≥12 weeks;
  7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
  8. Absence of severe hematologic, cardiac, pulmonary, hepatic, renal dysfunction, or immunodeficiency disorders. Within one week prior to the first administration, the functional status of vital organs must meet the following requirements (supportive therapies such as any blood components or cell growth factors are prohibited within 14 days before the first dose):

    1. Complete blood count: HGB ≥ 90 g/L; WBC ≥ 4.0 × 10⁹/L; NEUT ≥ 2.0 × 10⁹/L; PLT ≥ 100 × 10⁹/L;
    2. Blood biochemistry: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN; BUN and Cr ≤ 1.5 × ULN with creatinine clearance ≥ 50 mL/min;
    3. Coagulation function: INR ≤ 1.5 × ULN; APTT ≤ 1.5 × ULN;
    4. Within 4 weeks prior to the first dose, cardiac ultrasound must demonstrate: left ventricular ejection fraction (LVEF)> 50%;
  9. Pregnancy test results must be negative in patients of childbearing age, with voluntary use of effective and reliable contraceptive measures during the study;
  10. Participants must voluntarily enroll in the study, sign an informed consent form, demonstrate good compliance, and agree to participate in follow-up visits.

Exclusion Criteria:

  1. Ovarian cancer, fallopian tube cancer, primary peritoneal cancer (e.g., germ cell tumors), or ovarian tumors with low malignant potential (e.g., borderline tumors) of non-epithelial origin;
  2. Previous receipt of antitumor therapy, including but not limited to radiotherapy, chemotherapy, surgery, targeted therapy, and immunotherapy (Note: lymph node dissection or biopsy performed for clinical staging purposes using tissue obtained via puncture biopsy or laparoscopic exploration is permitted);
  3. History of other malignancies within the past 5 years, excluding cured localized tumors (e.g., basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ);
  4. Participation in other drug clinical trials and use of investigational drugs within 4 weeks prior to enrollment;
  5. Administration of live attenuated vaccines within 4 weeks before initial dosing or planned during the study period;
  6. Known history of allergy to any component of this regimen;
  7. Subjects with active infectious diseases;
  8. Subjects with any severe and/or uncontrolled diseases;
  9. Active autoimmune diseases requiring systemic treatment within 2 years prior to study initiation, or autoimmune diseases at risk of recurrence; exceptions include: non-systemically treatable dermatoses (e.g., vitiligo, alopecia, psoriasis, or eczema); hypothyroidism due to autoimmune thyroiditis requiring only stable hormone replacement therapy; well-controlled type 1 diabetes mellitus; and conditions deemed by investigators unlikely to recur without external triggers;
  10. Pregnant or breastfeeding women, or women of childbearing potential with positive baseline pregnancy test results.
  11. According to the investigator's assessment, the patient has a severe comorbid condition that poses significant risks to safety or impedes participation in the study, including but not limited to: severe hypertension uncontrolled by medication (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100 mmHg), myocardial ischemia or myocardial infarction, severe arrhythmias, congestive heart failure grade ≥2, severe pulmonary dysfunction/disease, severe diabetes mellitus, or active infections;
  12. A documented history of neurological or psychiatric disorders, including epilepsy or dementia;
  13. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
  14. Known history of interstitial lung disease or non-infectious pneumonia;
  15. Diagnosis of immunodeficiency or ongoing systemic glucocorticoid therapy or any other form of immunosuppressive treatment;
  16. Presence of any condition increasing bleeding risk, such as severe hemorrhoids, acute gastritis, or gastric and duodenal ulcers;
  17. History of dysphagia or any gastrointestinal disorder affecting drug absorption;
  18. Any other circumstances deemed inappropriate for study participation by the investigator.

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

  • 主な目的:処理
  • 割り当て:なし
  • 介入モデル:単一グループの割り当て
  • マスキング:なし(オープンラベル)

武器と介入

参加者グループ / アーム
介入・治療
実験的:Study Medication Regimen
  1. Preoperative neoadjuvant therapy: Sunitinib: 37.5 mg, qd, orally; discontinuation required for at least 4 weeks prior to surgery; Olaparib: 300 mg, bid, every 3 weeks × 3 cycles; Epalolide and Torvori-mab: infusion of sunitinib and olaparib begins on day 22 of treatment, 5 mg/kg intravenous, every 3 weeks × 2 cycles.
  2. Patients who achieve CR/PR/SD after neoadjuvant therapy shall undergo intermediate tumor cytoreductive surgery; those assessed as PD-positive shall receive treatment for recurrent/metastatic ovarian cancer.
  3. Postoperative adjuvant therapy: 6 cycles of chemotherapy; maintenance therapy with etoposide combination antibody plus olaparib ± sunitinib, with etoposide combination antibody maintenance therapy lasting 1 year.
  1. Preoperative neoadjuvant therapy: Sunitinib: 37.5 mg, qd, orally; discontinuation required for at least 4 weeks prior to surgery; Olaparib: 300 mg, bid, every 3 weeks × 3 cycles; Epalolide and Torvori-mab: infusion of sunitinib and olaparib begins on day 22 of treatment, 5 mg/kg intravenous, every 3 weeks × 2 cycles.
  2. Patients who achieve CR/PR/SD after neoadjuvant therapy shall undergo intermediate tumor cytoreductive surgery; those assessed as PD-positive shall receive treatment for recurrent/metastatic ovarian cancer.
  3. Postoperative adjuvant therapy: 6 cycles of chemotherapy; maintenance therapy with etoposide combination antibody plus olaparib ± sunitinib, with etoposide combination antibody maintenance therapy lasting 1 year.

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Total resection rate (R0 resection rate)
時間枠:3-month
All macroscopically visible tumor tissues were surgically removed, and no cancer cells were found at the surgical margins under microscopic examination.
3-month

二次結果の測定

結果測定
メジャーの説明
時間枠
Objective Response Rate (ORR)
時間枠:12-month
refers to the proportion of patients whose tumor volume has decreased by 30% and maintained this reduction for more than four weeks, calculated as the sum of complete response (CR) and partial response (PR).
12-month
Disease Control Rate (DCR)
時間枠:12-month
refers to the proportion of all cancer patients receiving a specific treatment who exhibit tumor shrinkage or stabilization, with this condition persisting for a defined period.
12-month
Progression-Free Survival (PFS)
時間枠:12-month
refers to the time from randomization until the first occurrence of disease progression or death from any cause.
12-month
Pathological Complete Response rate (pCR rate)
時間枠:12-month
absence of infiltrating tumor cells upon microscopic examination after resection of the primary tumor;
12-month
Overall Survival (OS)
時間枠:12-month
refers to the time from randomization until death from any cause.
12-month
Adverse Events (AEs)
時間枠:12-month
Collect all adverse events occurring in all subjects from the date of signing the informed consent form until 28 days after discontinuation of medication, including clinical symptoms and abnormalities in vital signs or laboratory tests. Record their clinical manifestations, severity, occurrence time, duration, management measures, and prognosis, and assess their correlation with the investigational drug.
12-month

協力者と研究者

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スポンサー

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2026年6月1日

一次修了 (推定)

2027年12月31日

研究の完了 (推定)

2027年12月31日

試験登録日

最初に提出

2026年6月19日

QC基準を満たした最初の提出物

2026年6月19日

最初の投稿 (実際)

2026年6月25日

学習記録の更新

投稿された最後の更新 (実際)

2026年6月25日

QC基準を満たした最後の更新が送信されました

2026年6月19日

最終確認日

2026年6月1日

詳しくは

本研究に関する用語

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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