An Open-label, Single Arm, Phase II Trial of Niraparib in Combination With Anti-PD1 Antibody in Recurrent/ Advanced Stage Endometrial Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- Niraparib in Combination With Anti-PD1 Antibody
- Conditions
- Recurrent/ Advanced Stage Endometrial Cancer Patients
- Sponsor
- Sun Yat-sen University
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Overall respond rate
- Last Updated
- 4 years ago
Overview
Brief Summary
Endometrial carcinoma is the most common malignancy of the female reproductive tract. Most cases are diagnosed at an early stage due to the appearance of symptoms such as postmenopausal bleeding. However, endometrial carcinoma carries a poor prognosis when it recurs after previous definitive treatment or when diagnosed at an advanced stage.The 5-year survival rate for FIGO III is approximately 57-66% and for FIGO IV is approximately 10-20%.The combination of PARP（poly adenosine diphosphate-ribose polymerase）inhibitors and PD1/PD-L1 has the theoretical support of preclinical molecular biology. In recent years, a large number of basic studies and preclinical models have confirmed that this combination therapy has superimposed or even synergistic effects on multiple levels.This study intends to explore the efficacy and safety of anti-PD-1 antibody combined with niraparib in the treatment of recurrent or advanced endometrial cancer.
Detailed Description
This study is an open, multi-center, prospective single-arm Phase II study to study the effectiveness of niraparib combined with sintilimab in the treatment of recurrent/advanced endometrial cancer that has failed or cannot be tolerated by chemotherapy Sex and safety. The study intends to enroll 37 patients who have undergone histopathologically confirmed recurrence/advanced endometrial cancer who have experienced first-line and above chemotherapy failure or intolerance and received niraparib combined with sintilimab for treatment. The Simon two-stage design is used to estimate the sample size. For the first type of error, the value of α (one-sided) is 0.05, the value of β is 0.2, the test power is 0.8, and the ORR of the second-line chemotherapeutic drug is 15%. It is assumed that the objective population of niraparib combined with sintilimab in the treatment of the target subject population The remission rate was 35%. Nine cases were enrolled in the first stage. When the number of effective cases was ≤1, the combination therapy was considered to be no better than the single drug, and the trial was terminated. Otherwise, continue with the enrollment of 25 cases in the second stage. Assuming a loss rate of 10%, 37 subjects are expected to be enrolled in the trial.
Investigators
Jundong Li
professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •The subject understands the trial process, signs an informed consent form, and agrees to participate in the research
- •18-70 years of age and female;
- •Histologically confirmed endometrial epithelial carcinoma (including endometrioid adenocarcinoma, clear cell carcinoma, serous adenocarcinoma, dedifferentiated/undifferentiated endometrioid carcinoma), carcinosarcoma (excluding specific types of endometrial epithelial carcinoma such as small-cell neuroendocrine carcinoma), and excluding uterine sarcoma；
- •Recurrence or advanced endometrial cancer that is not suitable for local treatment. At least first-line chemotherapy has failed or is intolerant；Including the following
- •Patients with recurrent endometrial cancer have received at least first-line chemotherapy for recurrence, and imaging studies suggest disease progression during or after treatment
- •Advanced endometrial cancer (FIGO Stage III-IV) that has received neoadjuvant chemotherapy/adjuvant chemotherapy or radical concurrent radiotherapy and chemotherapy, disease progression during first-line chemotherapy or recurrence within 6 months of the end of first-line treatment
- •Patients with recurrent endometrial cancer cannot tolerate first-line chemotherapy
- •At least one measurable lesion by RECIST1.1 on CT;
- •Subjects provide formalin-fixed and paraffin-embedded tumor tissue samples for pathological consultation；
- •ECOG performance status 0-1;
Exclusion Criteria
- •Prior receipt of any PARP inhibitor;
- •Patients with other invasive cancers other than endometrial cancer within the first 5 years of enrollment, excluding complete treatment of various cancers in situ within 2 years, such as squamous cell skin cancer, breast cancer, etc.
- •The last systemic or radical antitumor therapy, including radiotherapy, chemotherapy, and targeted therapy (small molecule targeted therapy is within 2 weeks before the first administration), immunotherapy, and palliative radiation therapy for symptom control, was completed at least 2 weeks before the first administration.
- •Received Chinese patent medicines or Chinese herbal medicines or immunomodulatory drugs (thymus, interferon, interleukin, etc.) with anti-tumor effects 2 weeks before enrollment.
- •Have undergone major surgery within 4 weeks before the start of the study or are expected to undergo major surgery during the study period, or any surgical effects that have not yet recovered after the surgery.
- •Symptomatic, uncontrolled brain metastases or neumomeningeal metastases without the need for radiographic confirmation;Patients with spinal cord compression may still be considered if they received targeted treatment and have evidence of clinically stable \> for at least 28 days (controlled CNS metastases must have been treated with treatment such as radiation or chemotherapy at least 1 month prior to study entry;Patients should not develop new symptoms associated with central nervous system lesions or symptoms indicative of disease progression, and patients should either take a steady dose of hormones or do not need hormones.)
- •Uncontrollable pleural and ascites.
- •Any active autoimmune disease or a history of autoimmune diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, hepatitis, nephritis, the pituitary gland inflammation, vasculitis, uveitis, or need to accept the system of sex hormone therapy and/or immunosuppressive therapy in patients with asthma (such as the need of bronchodilator), except the following:In the last 2 years without systematic treatment vitiligo, alopecia, Graves disease, psoriasis or eczema, stable immune thyroiditis controlled with treatment, type I diabetes requiring only stable insulin, childhood asthma has been completely remission.
- •Immunosuppressant or systemic hormonal therapy (\>10mg/ d or other equivalent hormonal preparation) was being used for immunosuppressive purposes and continued to be used 2 weeks before enrollment. Topical and systemic use not exceeding \>10mg/ d or other equivalent hormonal preparation was permitted.
- •With active bleeding (need) researchers to evaluate bleeding caused by tumor, with bleeding tendency or bleeding risk (such as tumor involving the great vessels, important bronchus, unable to control the obvious bleeding after hemostatic treatment, not cured bronchiectasis), or blood coagulation function apparently unusual, is treated with thrombolysis and anticoagulation (including need long-term antiplatelet therapy).
Arms & Interventions
study arm
Sintilimab： 200mg i.v., d1, 21days one cycle Niraparib： 200mg p.o qd，d1-d21, 21days one cycle
Intervention: Niraparib in Combination With Anti-PD1 Antibody
Outcomes
Primary Outcomes
Overall respond rate
Time Frame: at 6 months
The primary objective of this study is to determine the preliminary efficacy of administration of niraparib in combination with sintilimab in the treatment of recurrent/ advanced stage endometrial cancer, as measured by the objective response rate (ORR), which is a combination of CR (the target lesion completely disappeared over 4 weeks) and PR (Target lesions were reduced by more than 30% for more than 4 weeks).
Secondary Outcomes
- DoR（duration of response）(at 6 months)
- Overall survival rate(at 6 months)
- TTR(at 6 months)
- Adverse reaction rate(30 days after completion of treatment)
- PFS(1 year)
- Disease Control Rate(at 6 months)