Recurrent/ Advanced Stage Endometrial Cancer PatientsPhase 2NCT04885413
An Open-label, Single Arm, Phase II Trial of Niraparib in Combination With Anti-PD1（Programmed Cell Death Protein 1） Antibody in Recurrent/ Advanced Stage Endometrial Cancer Patients
A Phase 2 study testing Niraparib in Combination With Anti-PD1 Antibody in people with Recurrent/ Advanced Stage Endometrial Cancer Patients, run by Sun Yat-sen University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Recurrent/ Advanced Stage Endometrial Cancer Patients
- What is being tested?
- Niraparib in Combination With Anti-PD1 Antibody
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2021to 1 Jun 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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;
- Life expectancy ≥ 16 weeks;
- Good organ function, including:
- Neutrophil count ≥1500/µL (no growth factor support treatment within 7 days of the start of the study treatment)
- Platelets ≥100,000/µL (Do not accept platelet transfusion and any form of platelet-increasing treatment within 2 weeks of the start of the study)
- Hemoglobin ≥90g/L (transfusion should not be received within 2 weeks from the beginning of study treatment, and EPO should be required for support treatment within 7 days)
- Serum creatinine ≤1.5 times the upper limit of normal, or creatinine clearance ≥60mL/min (according to the Cockcroft-Gault formula)
- Total bilirubin ≤1.5 times the upper limit of normal or direct bilirubin ≤1.0 times the upper limit of normal
- AST and ALT ≤2.5 times the upper limit of normal, liver metastasis must be ≤5 times the upper limit of normal
- Urinary protein ≤ (+), or 24-hour urine protein quantification is less than 1g
- Thyroid-stimulating hormone (TSH) ≤1xULN (if abnormal, also examine FT3, FT4, if normal, it can be included in the group)
- Plasma cortisol ≤1xULN
- International normalized ratio (INR) and activated partial thromboplastin time≤1.5ULN (unless anticoagulant therapy is being used due to disease)
- The adverse effects of any previous treatment have returned to ≤CTCAE grade 1 or baseline, except for symptomatically stable sensory neuropathy or hair loss ≤CTCAE grade 2, except for anemia.
- Previous hormonal or immunotherapy was permitted.
- Women of reproductive age who had a negative pregnancy test at the time of enrolment and who committed to use adequate and effective contraception or abstinence for the period from the beginning to the end of the study and for a period of 3 months after the last administration of the study medication were eligible for enrolment
Who cannot join
- 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.)
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- 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).
- Thrombosis or embolism events in the past 6 months, such as cerebral vascular accident (including transient ischemic attack), pulmonary embolism;
- Severe cardiovascular disease or medical history includes but not limited to the following:
- NYHA (New York Heart Association) grade 3 and 4 congestive heart failure within 6 months before enrollment.
- Suffered from unstable angina or newly diagnosed angina or myocardial infarction within 12 months before screening.
- Arrhythmia requiring therapeutic intervention (Patients taking β-blockers or digoxin can be included in the group).
- Valvular heart disease with CTCAE≥2.
- Poorly controlled hypertension (systolic blood pressure> 150 mmHg or diastolic blood pressure> 100 mmHg;
- Patients with moderate or above pulmonary dysfunction that cannot be relieved, interstitial pulmonary disease or active pulmonary tuberculosis;
- Patients with active ulcers, intestinal perforation, unmitigated intestinal obstruction, and a history of gastrointestinal perforation during the 28 days prior to study enrollment.
- Active inflammatory bowel disease, uncontrollable nausea and vomiting, inability to swallow study medication, any gastrointestinal disease that may interfere with drug absorption and metabolism;
- Active infections such as human immunodeficiency virus, syphilis, untreated active hepatitis (HBV DNA copy number greater than 1000IU/ml, HCV RNA positive), etc.
- Severe infection occurred 4 weeks before first administration;
- Other serious or uncontrolled diseases.
- Have received live vaccine or live attenuated vaccine 30 days before the first administration;
- People who are known to be allergic to active or inactive ingredients of the study drug or a drug with a similar chemical structure;Patients who are pregnant or breastfeeding, or who are expected to become pregnant during the study treatment period;
- Other laboratory abnormalities:
- Uncorrectable hyponatremia (sodium <130 mmol/L; serum potassium <3.5 mmol/L);
- Any prior or current disease, treatment, or laboratory abnormality that may interfere with the results of the study and affect the patient's full participation in the study, or that the investigator considers the patient unsuitable for participation in the study;
- Any situation that the investigator deems unsuitable for participation, including poor understanding and coordination.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Centre
Guangzhou, Guangdong, 510060
Jundong Li, +86-20-87343104, lijd@sysucc.org.cn
About this study
Official title: An Open-label, Single Arm, Phase II Trial of Niraparib in Combination With Anti-PD1 Antibody in Recurrent/ Advanced Stage Endometrial Cancer Patients
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.
Read the 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.
- Being tested
- Niraparib in Combination With Anti-PD1 Antibody
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Niraparib in Combination With Anti-PD1 AntibodyDrug
Also called sintilimab
Sintilimab： 200mg i.v., d1, 21days one cycle Niraparib： 200mg p.o qd，d1-d21, 21days one cycle
| Study group | Role | What they receive |
|---|---|---|
| study arm | Experimental | Sintilimab： 200mg i.v., d1, 21days one cycle Niraparib： 200mg p.o qd，d1-d21, 21days one cycle Receives: Drug: Niraparib in Combination With Anti-PD1 Antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall respond rate
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).
Measured: at 6 months
Secondary outcomes (6)
DoR（duration of response）
From the start of Niraparib in Combination With sintilimab Antibody until progression or unacceptable toxicity.
Measured: at 6 months
PFS
Progression free survival
Measured: 1 year
Overall survival rate
Overall survival is defined as the time from registration to death from any cause, and subjects who are thought to be alive at the time of final analysis will be censored at the last date of contact.
Measured: at 6 months
Disease Control Rate
The total proportion of subjects who have an objective tumor response (CR + PR+SD) using the RECIST criteria.
Measured: at 6 months
TTR
Time to objective response
Measured: at 6 months
Adverse reaction rate
As determined by CTCAE v5.0 in subjects with recurrent /advanced stage endometrial cancer receiving combination of niraparib and sintilimab
Measured: 30 days after completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2021
- Study start1 Jul 2021
- Primary completion30 Aug 2022 (estimated)
- Study completion1 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent/ Advanced Stage Endometrial Cancer PatientsStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jundong Li, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04885413
- Sponsor's protocol ID
- SINI
- Status last verified
- Aug 2021
- First submitted
- 11 May 2021
- Last updated
- 23 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single Arm, Phase II Trial of Niraparib in Combination With Anti-PD1 Antibody in Recurrent/ Advanced Stage Endometrial Cancer Patients
- ClinicalTrials.gov ID
- NCT04885413
- Acronym / sponsor ID
- SINI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 30 Aug 2022 (estimated)
- Study completion
- 1 Jun 2023 (estimated)
- First posted
- 13 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| study arm | Experimental | Drug: Niraparib in Combination With Anti-PD1 AntibodySintilimab： 200mg i.v., d1, 21days one cycle Niraparib： 200mg p.o qd，d1-d21, 21days one cycle |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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
- At least one measurable lesion by RECIST1.1 on CT;
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Niraparib in Combination With Anti-PD1 AntibodyAlso: sintilimabSintilimab： 200mg i.v., d1, 21days one cycle Niraparib： 200mg p.o qd，d1-d21, 21days one cycle | Drug | study arm |
Primary outcome
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).
6 secondary outcomes
DoR（duration of response）
Time frame: at 6 months
PFS
Time frame: 1 year
Overall survival rate
Time frame: at 6 months
Disease Control Rate
Time frame: at 6 months
TTR
Time frame: at 6 months
Adverse reaction rate
Time frame: 30 days after completion of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2021.
- Individual participant dataSharing planned: Yes
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A Study of Dostarlimab in Combination With Carboplatin-paclitaxel in Japanese Participants With Primary Advanced or Recurrent Endometrial Cancer
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Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
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Selinexor in Maintenance Therapy After Systemic Therapy for Participants With p53 Wild-Type, Advanced or Recurrent Endometrial Carcinoma
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Niraparib in Combination With Anti-PD1 Antibody in people with Recurrent/ Advanced Stage Endometrial Cancer Patients, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall respond rate (time frame: at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2021.