Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
In the past few decades, the incidence of endocervical adenocarcinomas (ECAs) has been on the rise both in absolute numbers and overall proportion in cervical cancers. ECAs remain a significant public health problem despite advances in treatment options. Patients with ECA have a poorer survival rate than patients with squamous cell carcinoma (SCC), especially in patients with metastatic tumors. In the newly published 2020 World Health Organization (WHO) Classification of Female Genital Tumors, ECAs are subclassified into human papillomavirus-associated (HPVA) and human papillomavirus-independent (HPVI) groups. Meanwhile, PD-1/PD-L1 immunotherapy has been approved for the treatment of advanced cervical cancer, but there are still many deficiencies. Therefore, the investigators plan to use the new classification of female genital tumors and conduct a clinical trial to explore the safety and effectiveness of compound kushen injection combined with pabolizumab in the treatment of metastatic, recurrent, persistent cervical adenocarcinoma.
In this study, PD-1 inhibitors (pabolizumab) combined with compound kushen injection were used to treat metastatic, recurrent, persistent cervical adenocarcinoma, and the efficacy and safety of the two drugs were evaluated.
Participants who meet the requirements will sign the informed consent and be enrolled voluntarily. This project is a single-arm study without a control group. Forty-two patients are expected to be enrolled.
Two scoring systems, the combined positive score (CPS) and the tumor proportion score (TPS), are used for evaluation of PD-L1 expression of solid tumors. Through the measurable changes in the size of the lesions, the investigators can understand the changes of the disease. The primary endpoints were PFS and ORR. Whenever, for whatever reason, the subject does not complete the clinical trial observation, is considered to be an abscission case. When the subject falls off, the investigators must fill in the reason for the fall off in the CRF, and contact the subject as much as possible, complete the items that can be evaluated, and record the time of the last medication to prepare for the analysis of its efficacy and safety. The CRF should be kept for future reference.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| compound kushen injection combined with pabolizumab | Experimental | compound kushen injection 20ml/day and pabolizumab 200mg/21 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| compound kushen injection combined with pabolizumab | Drug | compound kushen injection 20ml/day and pabolizumab 200mg/21 days, both drugs are given intravenously |
|
| Measure | Description | Time Frame |
|---|---|---|
| ORR | To evaluate the objective response rate (CR + PR) of compound kushen injection combined with pabolizumab in patients with cervical adenocarcinoma. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| PFS | progression-free survival | 6 months |
| DCR | disease control rate | 6 months |
Not provided
Inclusion Criteria:
Exclusion Criteria:
1. Uncontrollable nausea and vomiting, inability to swallow research drugs, and any gastrointestinal disorders that may interfere with the metabolism of the drug.
2. Active viral infections such as human immunodeficiency virus, hepatitis B, hepatitis C, etc.
3. Uncontrolled major seizures, unstable spinal cord compression, superior vena cava syndrome, or other mental illnesses that prevent patients from signing informed consent.
4. Immunodeficiency (except splenectomy), or other diseases that the investigator believes may expose patients to high-risk toxicity.
9. History of bleeding and thrombosis:
10. Serious cardiovascular history:
11. Poorly controlled hypertension (systolic blood pressure> 150 mmHg or diastolic blood pressure> 100 mmHg).
12. Other laboratory inspection abnormalities:
13. Any previous or current disease, treatment, or laboratory abnormality that may interfere with the results of the study, affect the patient's full participation in the study, or the investigator believes that the patient is not suitable to participate in the study; the patient may not receive platelets within 4 weeks before the study drug begins Red blood cell infusion.
14. Patients who are pregnant or breastfeeding, or plan to become pregnant during study treatment.
15. Corrected QTc interval (QTc)> 450 milliseconds; if the patient has a prolonged QTc interval, but the investigator evaluates that the reason for the prolongation is a pacemaker (and no other cardiac abnormalities), it is necessary to discuss with the investigator to determine whether the patient is suitable Group study.
16. With any active autoimmune disease or have a history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo or asthma has been completely relieved in childhood and do not need any intervention after adulthood could be included; Asthma patient who need bronchodilators for medical intervention cannot be included) 17. Treatment with other immunosuppressive medications, systemic or topical corticosteroids (>10 mg daily prednisone or equivalent) within 14 days before enrollment.
18. With a history of severe allergic reaction to other monoclonal antibodies. 19. Evidence of central nervous system metastasis (such as brain edema requiring hormone intervention, or brain metastasis progression). Patients who have previously received treatment for brain or meningeal metastasis and persistently stable (MRI) for at least 1 month thus stopped systemic hormone therapy (dose > 10mg/ prednisone or other therapeutic hormones) for more than 2 weeks can be included.
20. Have previously received any PD-1/PD-L1 inhibitor treatment.
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lili Chen, MD | Contact | 8657187061501 | 5197004@zju.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Lili Chen, MD | Zhejiang University School of Medicine Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lili Chen | Hangzhou | Zhejiang | 310006 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34635081 | Background | Chen L, Niu Y, Wan X, Yu L, Zhang X, Strickland AL, Dong L, Zhou F, Lu W. Clinicopathological features and outcomes in gastric-type of HPV-independent endocervical adenocarcinomas. BMC Cancer. 2021 Oct 11;21(1):1095. doi: 10.1186/s12885-021-08792-7. | |
| 34455625 | Background | Chen L, Lucas E, Zhang X, Liu Q, Zhuang Y, Lin W, Chen H, Zhou F. Programmed death-ligand 1 expression in human papillomavirus-independent cervical adenocarcinoma and its prognostic significance. Histopathology. 2022 Jan;80(2):338-347. doi: 10.1111/his.14552. Epub 2021 Oct 13. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| DOR | duration of response | 6 months |
| 29095678 | Background | Frenel JS, Le Tourneau C, O'Neil B, Ott PA, Piha-Paul SA, Gomez-Roca C, van Brummelen EMJ, Rugo HS, Thomas S, Saraf S, Rangwala R, Varga A. Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial. J Clin Oncol. 2017 Dec 20;35(36):4035-4041. doi: 10.1200/JCO.2017.74.5471. Epub 2017 Nov 2. |
| 30943124 | Background | Chung HC, Ros W, Delord JP, Perets R, Italiano A, Shapira-Frommer R, Manzuk L, Piha-Paul SA, Xu L, Zeigenfuss S, Pruitt SK, Leary A. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2019 Jun 10;37(17):1470-1478. doi: 10.1200/JCO.18.01265. Epub 2019 Apr 3. |
| D009369 |
| Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |