Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy

Gastric Cancer Clinical Trial

Official title:

A Prospective, Multicenter, Randomized Controlled Study of Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05029453
• Other study ID #: PIONEER
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: August 26, 2021
• Est. completion date: March 3, 2023

Study information

• Verified date: August 2021
• Source: Wuhan Union Hospital, China
• Contact: Tao Zhang, Doctor
• Phone: (+86)18971656660
• Email: 1277577866[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is a multicenter, open-label, randomized controlled clinical study. The purpose of the study is to evaluate the efficacy and safety of apatinib combined with chemotherapy versus chemotherapy in second-line gastric cancer receiving prior anti-PD-1 therapy.

Description:

60 patients who meet the inclusion criteria will receive apatinib combine with chemotherapy or chemotherapy until the disease progresses or intolerable.

Apatinib: initial dose: 500mg,oral,once a day, after meal (try to take the medicine at the same time each day)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: March 3, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age: =18 years old, Female or Male;

2. Pathologically diagnosed gastric or gastroesophageal junction adenocarcinoma (GEJ).

3. Failure or intolerance of first-line chemotherapy which requires that the first-line chemotherapy regimen include the scheme based on anti-PD-1 drugs for no less than 2 months (Definition of treatment failure: intolerence of toxic side effects; disease progression during treatment; Or recurrence after the end of treatment.) Note: (1)The treatment of each line advanced disease includes one or more drugs with a medication time = 1 cycle. (2) Early adjuvant/neo-adjuvant therapy is allowed. If recurrence occurs during adjuvant/neoadjuvant therapy or within =24 weeks after completion, adjuvant/neoadjuvant therapy is considered to be a first-line pre-systemic chemotherapy for advanced disease. (3) Early-stage immunotherapy, combined chemotherapy or combined targeted drugs are allowed (except for VEGFR inhibitors).

4. Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria

5. ECOG performance status 0-1.

6. An expected survival of > 12 weeks.

7. Has adequate sufficient organ and bone marrow functions.

8. Patients whose adverse events caused by previous treatment have recovered to <= CTCAE 1 degree; And the interval between receiving nitroso or mitomycin =6 weeks; Receiving other cytotoxic drugs, radiotherapy or surgery = 4 weeks, and the wound has healed completely.

9. Fertile female subjects must undergo a serum-negative pregnancy test within 72 hours before starting the study drug

10. Patients have agreed and signed the informed consent. Willingness and able to follow the planned visit, research treatment, laboratory examination and other test procedures.

Exclusion Criteria:

1. It is known that it's allergic to any test drug and its excipients.

2. Previously received anti-angiogenic therapy, such as Ramucirumab and apatinib.

3. patients with uncontrolled large amount of exudate [chest, pericardium, abdominal cavity]

4. Patients with partial or complete gastrointestinal obstruction.

5. Hypertension, which cannot be well controlled by antihypertensive drugs (systolic blood pressure = 140 mmHg or diastolic blood pressure = 90 mmHg).

6. Patients with uncontrolled clinical symptoms or diseases of the heart.

7. In the first 3 months of the study, patients who had significant clinical bleeding symptoms or had definite bleeding tendency; History of gastrointestinal perforation and/or fistulae within 6 months prior to medications.

8. Long term use of aspirin, clopidogrel and other antiplatelet drugs, or warfarin and other anticoagulants;

9. Received other therapy within 4 weeks.

10. The patients who received systemic treatment with Chinese herbal medicine or immunomodulatory drugs

11. According to the research's judgement, there are patients who seriously endanger the safety of patients or affect the patients who complete.(such as uncontrolled hypertension?diabetes?thyroid disease, etc)

12. The patient has a serious or non healing wound or peptic ulcer or bone fracture;

13. A patient with other malignancies within 3 years.

14. patients whose adverse events (except hair loss) caused by previous treatment have not recovered to <= CTCAE 1 degree;

15. The researchers considered unsuitable for inclusion.

Related Conditions & MeSH terms

• Gastric Cancer
• Randomized Controlled Study
• Stomach Neoplasms

Intervention

Drug:
• Apatinib
In experimental group, the drug used with apatinib and chemotherapy.

Locations

Country	Name	City	State
China	Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (2)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China	Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

References & Publications (11)

Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014 Sep 11;513(7517):202-9. doi: 10.1038/nature13480. Epub 2014 Jul 23. — View Citation

Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, Dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-39. doi: 10.1016/S0140-6736(13)61719-5. Epub 2013 Oct 3. — View Citation

Harada D, Takata K, Mori S, Kozuki T, Takechi Y, Moriki S, Asakura Y, Ohno T, Nogami N. Previous Immune Checkpoint Inhibitor Treatment to Increase the Efficacy of Docetaxel and Ramucirumab Combination Chemotherapy. Anticancer Res. 2019 Sep;39(9):4987-4993. doi: 10.21873/anticanres.13688. — View Citation

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4. Erratum in: CA Cancer J Clin. 2011 Mar-Apr;61(2):134. — View Citation

Park SE, Lee SH, Ahn JS, Ahn MJ, Park K, Sun JM. Increased Response Rates to Salvage Chemotherapy Administered after PD-1/PD-L1 Inhibitors in Patients with Non-Small Cell Lung Cancer. J Thorac Oncol. 2018 Jan;13(1):106-111. doi: 10.1016/j.jtho.2017.10.011. Epub 2017 Oct 31. — View Citation

Salati M, Di Emidio K, Tarantino V, Cascinu S. Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer? ESMO Open. 2017 Jul 19;2(3):e000206. doi: 10.1136/esmoopen-2017-000206. eCollection 2017. Review. — View Citation

Schvartsman G, Peng SA, Bis G, Lee JJ, Benveniste MFK, Zhang J, Roarty EB, Lacerda L, Swisher S, Heymach JV, Fossella FV, William WN. Response rates to single-agent chemotherapy after exposure to immune checkpoint inhibitors in advanced non-small cell lung cancer. Lung Cancer. 2017 Oct;112:90-95. doi: 10.1016/j.lungcan.2017.07.034. Epub 2017 Aug 3. — View Citation

Shi Q, de Gramont A, Grothey A, Zalcberg J, Chibaudel B, Schmoll HJ, Seymour MT, Adams R, Saltz L, Goldberg RM, Punt CJ, Douillard JY, Hoff PM, Hecht JR, Hurwitz H, Díaz-Rubio E, Porschen R, Tebbutt NC, Fuchs C, Souglakos J, Falcone A, Tournigand C, Kabbinavar FF, Heinemann V, Van Cutsem E, Bokemeyer C, Buyse M, Sargent DJ. Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: findings from the analysis and research in cancers of the digestive system database. J Clin Oncol. 2015 Jan 1;33(1):22-8. doi: 10.1200/JCO.2014.56.5887. Epub 2014 Nov 10. — View Citation

Shiono A, Kaira K, Mouri A, Yamaguchi O, Hashimoto K, Uchida T, Miura Y, Nishihara F, Murayama Y, Kobayashi K, Kagamu H. Improved efficacy of ramucirumab plus docetaxel after nivolumab failure in previously treated non-small cell lung cancer patients. Thorac Cancer. 2019 Apr;10(4):775-781. doi: 10.1111/1759-7714.12998. Epub 2019 Feb 27. — View Citation

Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. doi: 10.1016/S1470-2045(14)70420-6. Epub 2014 Sep 17. — View Citation

Yan Y, Cao S, Liu X, Harrington SM, Bindeman WE, Adjei AA, Jang JS, Jen J, Li Y, Chanana P, Mansfield AS, Park SS, Markovic SN, Dronca RS, Dong H. CX3CR1 identifies PD-1 therapy-responsive CD8+ T cells that withstand chemotherapy during cancer chemoimmunotherapy. JCI Insight. 2018 Apr 19;3(8). pii: 97828. doi: 10.1172/jci.insight.97828. eCollection 2018 Apr 19. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival [PFS]	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	36 months
Secondary	Objective tumor response rate [ORR]	ORR is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as best overall response according to radiological assessments.	1year
Secondary	disease control rate [DCR]	Investigators will assess treatment response according to Response Evaluation Criteria in Solid Tumors 1.1(RECIST1.1)	1year
Secondary	Duration of response [DoR]	Duration of response	1year
Secondary	overall survival [OS]	OS is defined as the length of time from random assignment to death or to last contact.	3year
Secondary	Adverse Events [AEs]	AEs are evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0	1year