Anlotinib Combined With Niraparib Dual Therapy in Platinum-resistant Recurrent Ovarian Clear Cell Carcinoma.

NCT05130515 | Completed Phase 2

• 1 other identifier: 2021-KY-016
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

According to the definition of National Comprehensive Cancer Network (NCCN), ovarian clear cell carcinoma (OCCC) is a less common subtype of epithelial ovarian cancer (EOC) . The preliminary trial ANNIE (NCT04376073) shows a promising efficacy and safety profile for the ANNIE combo (anlotinib+niraparib). There is limited progress in targeted therapy for those less common ovarian cancers. In this study (CC-ANNIE), we aim to evaluate the antitumor activity and safety of niraparib combined with anlotinib in patients with platinum-resistant or platinum-refractory OCCC.

Conditions

Platinum-resistant Recurrent Clear Cell Ovarian Cancer

Keywords

clear cell ovarian cancer; Platinum-resistant cancer; Niraparib; Anlotinib

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  The primary objective of this study is to determine the preliminary efficacy of administration of niraparib in combination with anlotinib in the treatment of platinum-resistant recurrent or platinum-refractory clear cell ovarian cancer, as measured by the objective response rate (ORR), which is a combination of CR (complete response, the target lesion completely disappeared over 4 weeks) and PR (partial response, the target lesions were reduced by more than 30% for more than 4 weeks).

  at 6 months

Secondary Outcomes (5)

• The frequency and severity of adverse events

  Baseline through 1.5 year

• Duration of response

  at 12 months

• Time to response

  at 6 months

• 24 weeks clinical benefit rate

  at 24 weeks

• Objective response rate of homologous recombination deficient group

  at 6 months

Study Arms (1)

Treatment group

EXPERIMENTAL

Niraparib 200mg po QD day1\~21, Anlotinib 10mg po QD day1\~14

Drug: Niraparib; Drug: Anlotinib

Interventions

Niraparib DRUG

Niraparib 200mg po QD, day1\~21

Treatment group

Anlotinib DRUG

Anlotinib 10mg po QD, day1\~14, 3 weeks/cycle

Treatment group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patients understood the test process, signed the informed consent form and agreed to participate in the study.
• \~70 years old, female.
• Histologically confirmed ovarian clear cell carcinoma.
• The patients received platinum-based chemotherapy after primary debulking surgery, and experienced a recurrence or progression during the therapy; or experienced a recurrence or progression within 6 months after at least 4 cycles platinum-based therapy; or experienced a recurrence within 6 months after the end of the last platinum-based chemotherapy.
• Definition of recurrence or progression: clearly documented radiographic progression or carbohydrate antigen (CA125) increased continuously (confirmed after 1 week) and accompanied by clinical symptoms or physical examination, indicating disease progression.
• It is allowed to receive no more than 1 non-platinum regimen between 2 platinum-based regimens; Patients with disease recurrence or progression during platinum-based therapy or patients whose time from platinum-based treatment (at least 4 cycles) to disease recurrence and progression is less than 6 months are allowed to receive no more than 1 systematic treatment regimen.
• Expected survival more than 16 weeks.
• ECOG (Eastern Cooperative Oncology Group) physical status score 0-1.
• Good organ function.
• Neutrophil counts ≥1500/µL
• Platelet counts ≥100,000/µL
• Hemoglobin ≥10g/dl
• Serum creatinine≤1.5 times of the upper limit value, or creatinine clearance rate ≥ 60ml/min (according to Cockcroft Gault formula)
• Total bilirubin≤1.5 times of the upper limit value or direct bilirubin ≤1.0 times of the upper limit value
• Aspartate transaminase and alanine transaminase≤ 2.5 times of the upper limit value, and ≤5 times of the upper limit value when liver metastasis exists

You may not qualify if:

• Any poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors treatment history.
• Allergy to active or inactive ingredients of niraparib or drugs with similar chemical structures.
• Allergy to active or inactive ingredients of anlotinib or drugs with similar chemical structures.
• Active and uncontrollable brain metastasis or leptomeningeal metastasis. Patients with spinal cord compression can still be considered if they have received targeted treatment and have evidence of clinical stability of the disease for at least \> 28 days (controlled brain metastasis must have received radiotherapy or chemotherapy at least 1 month prior to study entry; patients may not have new symptoms related to brain lesions or symptoms indicating disease progression and either take a stable dose of hormone or do not need to take hormone).
• Major surgery performed within 3 weeks before enrollment, or any surgical effects that have not been recovered from the surgery, or chemotherapy.
• \>20% bone marrow palliative radiotherapy performed within 1 week before enrollment.
• Any other malignant tumor exclude ovarian cancer has been diagnosed within 2 years before enrollment (except for completely treated basal or squamous cell skin cancer).
• Combined with central squamous cell carcinoma of lungs or at risk of massive hemoptysis (such as bronchiectasis and uncured tuberculosis).
• Myelodysplastic syndromes (MDS) or acute myelocytic leukemia (AML).
• Serious or uncontrollable diseases, including but not limited to:
• uncontrollable nausea and vomiting, inability to swallow the study drug, any gastrointestinal disease that may interfere with drug absorption and metabolism.
• active viral infections such as human immunodeficiency virus, hepatitis B, hepatitis C, etc.
• uncontrolled major seizures, unstable spinal cord compression, superior vena cava syndrome or other mental disorders that affect the patient's informed consent.
• immune deficiency (except splenectomy), or other diseases that researchers believe may expose patients to high-risk toxicity.
• Prone to bleeding and history of thrombosis:

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• Zai Lab (Shanghai) Co., Ltd.: collaborator
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, 510000, China

Location

MeSH Terms

Interventions

niraparib; anlotinib

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Drug: Niraparib Niraparib 200mg po QD day1\~21 Drug: Anlotinib Anlotinib 10mg po QD day1\~14.

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: November 23, 2021
• Study Start: December 15, 2021
• Primary Completion: January 1, 2023
• Study Completion: January 1, 2023
• Last Updated: January 31, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available, within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

CN (1)