- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT07627347
Efficacy and Safety of Anlotinib Combined With Bemocizumab for Neoadjuvant Therapy of Esophageal Squamous Cell Carcinoma(ESCC) (RAOS)
Clinical Trial on the Efficacy and Safety of Anlotinib Combined With Bemocizumab for Neoadjuvant Therapy of Resectable Esophageal Squamous Cell Carcinoma
Studieoversikt
Detaljert beskrivelse
This is a prospective, single-arm, single-center clinical study aimed at evaluating the efficacy and safety of anlotinib combined with bemarituzumab in neoadjuvant treatment for resectable esophageal squamous cell carcinoma, with the goal of improving the pathological complete response (pCR) rate and margin-negative resection(R0) resection rate in patients undergoing esophageal cancer surgery, as well as enhancing disease-free survival (DFS) in postoperative patients.
The study plans to enroll 25 eligible participants who meet the inclusion and exclusion criteria. Patients will receive 3-4 cycles of neoadjuvant therapy prior to surgery, consisting of bemarituzumab at 1200 mg every 3 weeks and anlotinib at 8 mg daily from day 1 to day 14. 。 Surgical eligibility will be assessed 4-6 weeks after completion of neoadjuvant therapy. Patients achieving complete response (CR), partial response (PR), or stable disease (SD) will undergo surgery. Patients with progressive disease (PD) who are deemed operable by the investigator will also proceed to surgery; otherwise, they will be withdrawn from the study. The surgical approach will typically involve a standard three-incision thoracoabdominal laparoscopic esophagectomy, although Ivor-Lewis or Sweet procedures may also be used as appropriate. Postoperative adjuvant therapy will be administered based on individual patient conditions.
Following surgery, pathological evaluation will be performed to determine the primary endpoint, pathologic complete response (pCR). Subsequent follow-up will continue for 5 years to assess other secondary endpoints.
Studietype
Registrering (Antatt)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiekontakt
- Navn: Zhizhi Wang, MD
- Telefonnummer: +8616676770718
- E-post: 347901213@qq.com
Studiesteder
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Guangdong
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Guangzhou, Guangdong, Kina, 510515
- Rekruttering
- Nanfang Hospital, Southern Medical University
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Ta kontakt med:
- Zhizhi Wang, MD
- Telefonnummer: +8616676770718
- E-post: 347901213@qq.com
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
Inclusion Criteria:
- Aged 18-70, both male and female
- After gastroscopy/ultrasonic gastroscopy biopsy, the pathology suggests squamous cell carcinoma of the esophagus, and the clinical diagnosis is cT2N1-2M0 or cT3N0-2M0, with TNM staging of II-III B
- Patients with non-cervical esophageal cance
- The patient has not previously received systemic or local treatment for esophageal cancer, and according to the RECIST 1.1 criteria, there is at least one measurable lesion for imaging evaluation of neoadjuvant therapy
- ECOG PS: 0-1
- Expected survival duration ≥ 12 months
- The subjects had no functional disorders of major organs, and the researchers assessed that thyroid, lung, liver, kidney, and heart functions were basically normal;
- Women of childbearing age must have already taken reliable contraceptive measures or undergone a pregnancy test (serum or urine) within 7 days prior to enrollment, with a negative result, and be willing to use appropriate contraception during the trial and for 8 weeks after the last administration of the trial medication. For males, they must agree to use appropriate contraception during the trial and for 8 weeks after the last administration of the trial medication, or have undergone surgical sterilization
- The subjects voluntarily joined this study, signed the informed consent form, exhibited good compliance, actively cooperated with the planned schedule by returning to the hospital for regular clinical follow-ups and necessary treatments, and cooperated with the regular collection of blood and tissue samples
Exclusion Criteria:
- Within the past 5 years, there has been or is currently a co-occurrence of other malignant tumors, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invades the basement membrane)]
- Patients with ulcerative esophageal squamous cell carcinoma
- Patients with esophageal fistula or tracheal fistula;
- Those who are allergic to anlotinib and bemusuban
- Those with a history of immune deficiency, including HIV-positive or suffering from other acquired or congenital immune deficiency diseases, or those who have undergone organ transplantation
- Patients with any severe and/or uncontrolled diseases
- Unresolved toxic reactions above CTC AE Grade 1 caused by any previous treatment, excluding alopecia;
- Individuals with multiple factors affecting oral medication administration, such as inability to swallow, chronic diarrhea, and intestinal obstruction
- Urine routine test indicates proteinuria ≥++ and confirmed 24-hour urine protein quantitation > 1.0 g
- Subjects who underwent major surgical procedures, incisional biopsies, or significant traumatic injuries within 28 days prior to grouping
- Abnormal coagulation function: INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5ULN), with a tendency to bleed or undergoing thrombolytic or anticoagulant therapy; patients who have experienced any bleeding or hemorrhagic events ≥ CTCAE Grade 3 within 4 weeks before grouping, have unhealed wounds, ulcers, or fractures
- Those who have experienced arterial or venous thromboembolic events within 6 months, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism
- Pregnant or lactating women
- Patients with distant metastasis
- Patients with significant bone marrow suppression
- Suffering from mental illness or having a history of abuse of psychotropic drugs;
- Patients who have participated in other drug clinical trials within 4 weeks;
- Patients with concomitant diseases that, according to the researcher's judgment, pose serious risks to patient safety or affect patients' ability to complete the study
- Individuals with hereditary bleeding tendency, coagulation dysfunction, potential invasion of large blood vessels, and other bleeding risks, who have experienced clinically significant bleeding symptoms or have a clear tendency to bleed within the previous 3 months before enrollment, such as gastrointestinal bleeding, bleeding gastric ulcer, and baseline fecal occult blood test result of ++ or above
- Researchers consider those who are not suitable for inclusion
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
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Eksperimentell: Anlotinib+ Bevacizumab group
Received neoadjuvant therapy for 3-4 cycles before surgery, with the specific regimen as follows: bevacizumab, 1200mg q3w; anlotinib, 8mg qd d1-d14
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Received neoadjuvant therapy for 3-4 cycles before surgery, with the specific regimen as follows: bevacizumab, 1200mg q3w; anlotinib, 8mg qd d1-d14
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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PCR
Tidsramme: Perioperative
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The measurement method for pathological complete response rate (pCR rate) involves pathological examination after surgical resection to confirm the absence of any viable tumor cells in the primary lesion and regional lymph nodes, which is denoted as "1".
If this criterion is not met, it is denoted as "0".
The final calculation is based on the percentage of patients achieving pCR out of the total number of patients.
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Perioperative
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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OS
Tidsramme: up to 5 years
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Overall survival time
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up to 5 years
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R0 margin-negative resection rate
Tidsramme: Perioperative
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margin-negative resection rate
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Perioperative
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Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: Xuguang Rao, PhD., Nanfang Hospital, Southern Medical University
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, Yang Z, Li H, Zou X, He J. Cancer incidence and mortality in China, 2014. Chin J Cancer Res. 2018 Feb;30(1):1-12. doi: 10.21147/j.issn.1000-9604.2018.01.01.
- Fukuoka S, Hara H, Takahashi N, Kojima T, Kawazoe A, Asayama M, Yoshii T, Kotani D, Tamura H, Mikamoto Y, Hirano N, Wakabayashi M, Nomura S, Sato A, Kuwata T, Togashi Y, Nishikawa H, Shitara K. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). J Clin Oncol. 2020 Jun 20;38(18):2053-2061. doi: 10.1200/JCO.19.03296. Epub 2020 Apr 28.
- Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-1098. doi: 10.1016/S1470-2045(15)00040-6. Epub 2015 Aug 5.
- Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. doi: 10.1200/JCO.2018.79.1483. Epub 2018 Aug 8.
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
- Update results of anlotinib combined with TQB2450 (PD-L1 blockade) as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): a single-arm, multicenter, open-label phase Ⅱ clinical trial.2023 ESMO.1531P.
- Updated results of a phase II clinical trial: paclitaxel and carboplatin plus PD-1 blockades combined with anlotinib as first-line treatment for advanced esophageal cancer.2023ESMO 1542P.
- Xiaolin Lin, Qing Xia, Ting Han, et al. Efficacy and safety of toripalimab combination with SOX regimen as a first-line treatment in patients with unresectable locally advanced or recurrent/metastatic gastric/gastroesophageal junction cancer: Preliminary data from a single-armed, exploratory study.2022 ASCO e16015
- Martin Reck et al. atezolizumab (atezo) + bevacizumab (bev) and chemotherapy in first-line (1L) metastatic nonsquamous (nsq) non-small cell lung cancer (NSCLC) across key subgroups. 2022 AACR Abstract CT216
- Abnet CC, Arnold M, Wei WQ. Epidemiology of Esophageal Squamous Cell Carcinoma. Gastroenterology. 2018 Jan;154(2):360-373. doi: 10.1053/j.gastro.2017.08.023. Epub 2017 Aug 18.
- Young K, Chau I. Targeted Therapies for Advanced Oesophagogastric Cancer: Recent Progress and Future Directions. Drugs. 2016 Jan;76(1):13-26. doi: 10.1007/s40265-015-0510-y.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- NFEC-2026-220
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
IPD-delingstidsramme
Tilgangskriterier for IPD-deling
IPD-deling Støtteinformasjonstype
- CSR
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