Anlotinib and Niraparib Dual Therapy Evaluation in Platinum-resistant Recurrent Ovarian Cancer

NCT ID: NCT04376073

Last Updated: 2020-11-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-22
• Study Completion Date: 2022-03-31

Brief Summary

At present, the standard treatment for platinum-resistant ovarian cancer patients is platinum-free chemotherapy, with poor efficacy and tolerance. The combination of anti-angiogenic drugs and PARPi can play a synergistic anti-tumor role and achieve good efficacy in platinum-sensitive recurrent ovarian cancer. This study intends to explore the safety and effectiveness of anlotinib and niraparib dual therapy in patients with platinum-resistant recurrent ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (ovarian cancer).

Detailed Description

The present study is an open, single-center, prospective, single-arm phase II study to investigate the efficacy and safety of nilapalil combined with anrotidine in the treatment of platinum-resistant recurrent ovarian cancer. In this study, 40 histopathologically diagnosed patients with high-grade serous ovarian, fallopian tube and primary peritoneal cancer were treated with neelapalil plus anrotinib in patients who underwent first-line chemotherapy or above and had a recurrence of platinum-resistant chemotherapy (the time of tumor progression of the last platinum-containing chemotherapy < 6 months). The study will be divided into two phases. The first phase will include six patients on a 21-day cycle (nierapalil 200mg QD*21; Anrotidine 12mg qd d1-14, d15-21 suspension), all subsequent patients were enrolled if no more than dose-restricted toxic event occurred within a cycle, and the combination treatment was continued until the disease progressed or the toxicity was intolerable.

Conditions

Platinum-resistant Ovarian Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment group

Niraparib 300mg(Body Weigh ≥77 kg)/200mg (Body Weigh <77 kg) po QD day1~21, Anlotinib 12mg po QD day1~14.

Starting dose of anlotinib changed to 10mg from 2020-11-13.

Group Type: EXPERIMENTAL

Niraparib

Intervention Type: DRUG

Niraparib 300mg(Body Weigh ≥77 kg)/200mg (Body Weigh \<77 kg) po QD day1\~21, Anlotinib 12mg po QD day1\~14

Anlotinib

Intervention Type: DRUG

Anlotinib 12mg po QD day1\~14. Starting dose of anlotinib changed to 10mg from 2020-11-13.

Interventions

Niraparib

Niraparib 300mg(Body Weigh ≥77 kg)/200mg (Body Weigh \<77 kg) po QD day1\~21, Anlotinib 12mg po QD day1\~14

Intervention Type: DRUG

Anlotinib

Anlotinib 12mg po QD day1\~14. Starting dose of anlotinib changed to 10mg from 2020-11-13.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Subjects understand the trial process, sign informed consent, agree to participate in the study, and have the ability to follow the protocol; 2. 18 ~ 70 years old (inclusive), female; 3. Histologically diagnosed ovarian, fallopian tube, or primary peritoneal cancer; 4. Subjects were initially treated with platinum, and the disease recurrence occurred within 6 months after the end of the previous platinum-containing chemotherapy, that is, platinum resistance relapsed; 5. Life expectancy > 16 weeks; 6. Patient's ECOG physical status score is 0-1; 7. Subject agrees to take blood samples for gBRCA mutations; 8. Can provide formalin-fixed, paraffin-embedded tumor tissue samples for sBRCA and homologous recombination repair-related genes detection (optional); 9. Good organ function, including:
• Neutrophil count >= 1500 / μL;
• Platelets >= 100,000 / μL;
• Hemoglobin >= 9g / dL;
• Serum creatinine <= 1.5 times the upper limit of normal value, or creatinine clearance >= 60mL / min (calculated according to Cockcroft-Gault formula);
• Total bilirubin <= 1.5 times the upper limit of normal value or direct bilirubin <= 1.0 times the upper limit of normal value;
• AST and ALT <= 2.5 times the upper limit of normal value. When liver metastases are present, it must be <= 5 times the upper limit of normal value.

10. The toxic side effects of any previous chemotherapy have recovered to <= CTCAE level 1 or baseline levels, except for sensory neuropathy or hair loss with stable symptoms <= CTCAE level 2.

Exclusion Criteria

1. People who are known to be allergic to Niraparib or Anlotinib (or active or inactive ingredients of drugs with similar chemical structure);

2. Symptomatic, uncontrolled brain or pia mater metastases;

3. Underwent major surgery within 3 weeks before the study began or has not recovered after surgery;

4. Received palliative radiotherapy of > 20% bone marrow 1 week before enrollment;

5. Have invasive cancer other than ovarian cancer (except fully treated basal or squamous cell skin cancer) within 2 years before enrollment;

6. Patients with central lung squamous cell carcinoma or at risk for large hemoptysis;

7. Previous or currently diagnosed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML);

8. Severe or uncontrolled diseases, including but not limited to: uncontrollable nausea and vomiting, inability to swallow or gastrointestinal diseases that may interfere with drug absorption and metabolism; active viral infections; mental illnesses that affect patients' signed informed consent History of bleeding tendency and thrombosis; history of severe cardiovascular disease;

9. Laboratory abnormalities: hyponatremia; hypokalemia; uncontrollable nail function abnormalities;

10. Receive platelet or red blood cell transfusions within 4 weeks;

11. Patients who are pregnant or nursing, or who plan to become pregnant during study treatment;

12. Have previously received any PARP inhibitor treatment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Jihong Liu

OTHER

Sponsor Role: lead

Responsible Party

Jihong Liu

professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Facility Contacts

guochen liu, Dr

Role: primary

References

Deng T, Yan L, Li J, Liu G, Yin A, Feng Y, Zheng M, Zhang C, Huang H, Huang Q, Lin A, Jiang J, Kong B, Liu J. Adverse Event Management in Patients with Platinum-Resistant Ovarian Cancer Treated with Niraparib and Anlotinib: Updates from the Phase II, Multi-Center ANNIE Study. Ther Clin Risk Manag. 2025 Jul 21;21:1135-1147. doi: 10.2147/TCRM.S526755. eCollection 2025.

Reference Type: DERIVED

PMID: 40718116 (View on PubMed)

Liu G, Feng Y, Li J, Deng T, Yin A, Yan L, Zheng M, Xiong Y, Li J, Huang Y, Zhang C, Huang H, Wan T, Huang Q, Lin A, Jiang J, Kong B, Liu J. A novel combination of niraparib and anlotinib in platinum-resistant ovarian cancer: Efficacy and safety results from the phase II, multi-center ANNIE study. EClinicalMedicine. 2022 Nov 30;54:101767. doi: 10.1016/j.eclinm.2022.101767. eCollection 2022 Dec.

Reference Type: DERIVED

PMID: 36583171 (View on PubMed)

Other Identifiers

2019-FXY-357

Identifier Type: -

Identifier Source: org_study_id