Chemotherapy Combined With Apatinib and PD-1 Antibody

Gastric Cancer Clinical Trial

Official title:

Chemotherapy Combined With Apatinib and PD-1 Monoclonal Antibody for Second-line or Above Treatment of Advanced Gastric Cancer-A Prospective, Single-arm, Open, Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05025033
• Other study ID #: TJMUCH-GI-GC01
• Status: Completed
• Phase: Phase 2
• Start date: May 30, 2019
• Est. completion date: April 30, 2022

Study information

• Verified date: January 2021
• Source: Tianjin Medical University Cancer Institute and Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The effective rate of second-line and later-line single-agent therapy for advanced gastric cancer is limited. This research plan aims to explore whether the combination of drugs can further improve the benefits of second-line and above therapies. Previous studies have shown that there is a significant synergistic effect between chemotherapy and PD-1 monoclonal antibody, or anti-angiogenic TKI drugs and PD-1 monoclonal antibody. This project is planned to be based on the classic chemotherapy drugs irinotecan or paclitaxel, combined with mesylate Apatinib and PD-1 monoclonal antibody, explore the effectiveness and safety of this three-drug combination regimen for the second-line and above treatment of advanced gastric cancer, in order to provide a better late-line treatment plan for patients with advanced gastric cancer.

Description:

This study is a prospective, single-center, single-arm phase II clinical study, which aims to explore the efficacy of PD-1 antibody combined with apatinib combined with chemotherapy as a second-line and above regimen in the treatment of advanced gastric cancer.The enrolled patients were patients with advanced inoperable gastric cancer or gastroesophageal junction adenocarcinoma who had advanced first-line fluorouracil combined with platinum or advanced second-line paclitaxel and irinotecan, with an ECOG PS of 0-1. Treatment plan: PD-1 antibody: 200mg intravenous drip every 3 weeks; Apatinib 250mg/day; Chemotherapy: Irinotecan 150mg/m2, intravenous drip every 2 weeks, or Paclitaxel 150mg/m2, intravenous drip, once every 3 weeks. An imaging evaluation is performed every 6-8 weeks. Monitor blood routine, blood biochemistry, electrocardiogram, urine routine, thyroid function, heart function according to clinical routine, and record adverse events. Primary observational endpoints: objective effective rate (ORR), progression-free survival time (PFS), secondary observational endpoints: overall survival time (OS), disease control rate (DCR) and safety, and dynamic monitoring of serum biomolecular markers for exploration study .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 30, 2022
• Est. primary completion date: January 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Patient age =18 years old;

1. The ECOG score is 0-1 points;

2. Patients with locally advanced gastric cancer or GEJ adenocarcinoma who have been histologically confirmed, metastatic or unresectable;

3. Have received at least one systemic chemotherapy regimen in the past and have progressed; or have received adjuvant chemotherapy, but the disease has progressed or relapsed within 6 months after the end of the treatment; have not used any of the drug treatments in this study;

4. There are measurable lesions that meet the RECIST 1.1 standard;

5. It has sufficient organ and bone marrow function, and the laboratory examination meets the following requirements: a.HGB=90g/L;b.NEUT=1.5×109/L;c.PLT =100×109/L;d. BIL=1.5 times the upper limit of normal (ULN);e. ALT and AST=2.5×ULN; liver metastasis, then ALT and AST=5×ULN;f. Endogenous creatinine clearance rate =50ml/min (Cockcroft-Gault formula);g. Urine routine is normal, or urine protein <(++), or 24-hour urine protein <1.0 g;

6. Normal blood coagulation, no active bleeding and thrombosis: a. International normalized ratio INR=1.5;b. Partial thromboplastin time APTT=1.5 ULN;

7. Women of childbearing age must undergo a negative pregnancy test (serum or urine) within 14 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug; for men, it should be surgery Sterilize or agree to use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug;

8. Estimated survival period = 3 months;

9. The patient voluntarily joined the study and signed an informed consent form (ICF);Those who are expected to have good compliance can follow up the efficacy and adverse reactions as required by the protocol.

Exclusion Criteria:

1. Have received anti-angiogenesis drug therapy in the past;

2. Have received anti-PD-1 and anti-PD-L1 antibody drug therapy in the past;

3. Patients with high blood pressure who cannot be reduced to the normal range by antihypertensive drugs (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg), coronary heart disease above grade I, grade I arrhythmia (including QTc interval prolongation) Male>450 ms, female>470 ms) and grade I cardiac insufficiency;

4. There are many factors that affect oral drugs (such as inability to swallow and intestinal obstruction, etc.);

5. Allergic to the drugs in this program;

6. Patients with a clear gastrointestinal bleeding tendency, including the following conditions: local active ulcer lesions, and fecal occult blood (+ +) cannot be included in the group; patients with a history of melena and hematemesis within 1 month;

7. Patients with contraindications to apatinib: For patients with active bleeding, intestinal perforation, intestinal obstruction, within 30 days after major surgery, drug-uncontrollable hypertension, grade ?-? cardiac insufficiency (NYHA standard), severe liver and kidney Patients with dysfunction (Grade 4); If you have immune system diseases, you need to use a daily dose of dexamethasone above 10mg;

8. According to the judgment of the investigator, patients with concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study;

9. The researcher believes that it is not suitable for inclusion.

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• PD-1 antibody, paclitaxel or irinotecan, Apatinib mesylate
PD-1 antibody 200mg intravenous drip every 3 weeks; Apatinib 250mg/day; Chemotherapy: Irinotecan 150mg/m2, intravenous drip every 2 weeks, or Paclitaxel 150mg/m2, intravenous drip, once every 3 weeks.

Locations

Country	Name	City	State
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Tianjin Medical University Cancer Institute and Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

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Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, Hara H, Golan T, Garrido M, Jalal SI, Borg C, Doi T, Yoon HH, Savage MJ, Wang J, Dalal RP, Shah S, Wainberg ZA, Chung HC. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer. 2019 Jul;22(4):828-837. doi: 10.1007/s10120-018-00909-5. Epub 2019 Mar 25. — View Citation

Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018 May 10;4(5):e180013. doi: 10.1001/jamaoncol.2018.0013. Epub 2018 May 10. Erratum In: JAMA Oncol. 2019 Apr 1;5(4):579. — View Citation

Hughes PE, Caenepeel S, Wu LC. Targeted Therapy and Checkpoint Immunotherapy Combinations for the Treatment of Cancer. Trends Immunol. 2016 Jul;37(7):462-476. doi: 10.1016/j.it.2016.04.010. Epub 2016 May 20. — View Citation

Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. doi: 10.1016/S0140-6736(17)31827-5. Epub 2017 Oct 6. — View Citation

Kawazoe A, Fukuoka S, Nakamura Y, Kuboki Y, Wakabayashi M, Nomura S, Mikamoto Y, Shima H, Fujishiro N, Higuchi T, Sato A, Kuwata T, Shitara K. Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. Lancet Oncol. 2020 Aug;21(8):1057-1065. doi: 10.1016/S1470-2045(20)30271-0. Epub 2020 Jun 23. — View Citation

Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, Wang Y, Yi X, Hu Z, Zou J, Wang Q. Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study. Clin Cancer Res. 2019 Jan 15;25(2):515-523. doi: 10.1158/1078-0432.CCR-18-2484. Epub 2018 Oct 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	biomolecular markers	Serum will be collected before medication and during each evaluation. Mass spectrometry or RNA sequencing technology will be used to detect the differences in the exosomal proteome and non-coding RNA group in the serum before medication. Screen out the group of exosomal protein/non-coding RNA components with obvious differences in the two groups of patients; and consider its biological function/signal pathway, and finally select 1-2 kinds of protein/non-coding RNA.	From the begaining of treatment, then every 2 months after treatment, until the last time after treatment, assessed up to 24 months
Primary	The Overall Response Rate	The proportion of CR and PR	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Primary	Progression Free Survival	Time from the start of treatment to the progression of the disease	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Secondary	Overall survival	Time from the start of treatment to the occurrence of death	From date of randomization until the date of death from any cause or the last visit date, whichever came first, assessed up to 60 months
Secondary	Disease Control rate	The proportion of CR,PR and SD	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary	adverse events	The incidence of various adverse events	Until 3 months after the end of the treatment