Trastuzumab, Bevacizumab with Paclitaxel for HER2-positive Gastric Cancer in a Second-line Therapy

NCT05640830 | Recruiting Phase 1

• 1 other identifier: TREAZURE
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open-label, prospective, phase 2 study of trastuzumab, bevacizumab, and paclitaxel as second-line treatment for patients with HER2-positive advanced gastric cancer who had progressed on first-line chemotherapy including trastuzumab or anti-HER2 agents.

Conditions

HER2-positive Advanced Gastric Cancer

Keywords

HER2-positive gastric cancer; trastuzumab, bevacizumab & paclitaxel

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Defined as the time from the start of treatment to the date of documented disease progression (according to RECIST 1.1) or death from any cause.

  up to 36 months

Study Arms (1)

TREAZURE

EXPERIMENTAL

This is a single arm study. Trastuzumab has been administered at 6 mg/kg every 3 weeks after initial loading of 8 mg/kg during the first anticancer treatment, so in the second anticancer treatment, 4 mg/kg is administered every 2 weeks to maintain the same concentration. Bevacizumab is administered at 5 mg/kg at 2-weekly intervals used in metastatic colorectal cancer. Paclitaxel is administered on a standard schedule of 80 mg/m2 for 3 consecutive weeks followed by a 1-week break as an existing weekly regimen, and when side effects occur, the weekly dose is reduced by 25% to 60 mg/m2 for 3 weeks or administered every 2 weeks. Administer 80 mg/m2. Administration of this drug is set as one cycle of 4 weeks.

Drug: trastuzumab, bevacizumab with paclitaxel (triple combination)

Interventions

trastuzumab, bevacizumab with paclitaxel (triple combination) DRUG

Trastuzumab 4 mg/kg Day 1, 15 Bevacizumab 5 mg/kg Day 1, 15 Paclitaxel 80 mg/m2 Day 1, 8, 15 every 4 weeks

TREAZURE

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• HER2-positive advanced gastric cancer
• Defined as IHC 2+, which is IHC 3+ or SISH + (or FISH) evaluated by laboratory tests. (SISH positivity is defined as the ratio of the HER2 gene copy number to the CEP17 signal ≥ 2.0)
• or significant overexpression of HER2 protein on target proteomic analysis (multiple reaction monitoring)
• Patients who have progressed in response to one systemic anticancer therapy for advanced gastric cancer
• Patients who are willing and able to write a written consent form for this trial.
• Patients aged 19 years or older at the time of signing the subject consent form.
• Patients with measurable or evaluable lesions according to RECIST 1.1.
• ECOG activity status 0, 1 or 2
• as patients with adequate organ function
• Absolute neutrophil (ANC) ≥1.0 x 109/L, platelet ≥100 x 109/L, hemoglobin ≥9 g/dL, serum creatinine ≤1.5 x ULN, total bilirubin ≤3.0 mg on laboratory tests within 2 weeks before starting treatment /dL, AST/ALT ≤5 x ULN
• Echocardiogram EF ≥55% or MUGA scan ≥50%

You may not qualify if:

• Patients who have received chemotherapy, radiation therapy, immunotherapy or targeted therapy for gastric cancer within the past 2 weeks.
• Patients who have experienced Grade 3-4 gastrointestinal bleeding within 3 months
• Patients who have experienced an arteriovascular embolism event, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular disorder, or unstable angina within 6 months
• Ongoing or active infection, symptomatic congestive heart failure, unstable angina, symptomatic or poorly controlled cardiac arrhythmias, uncontrolled thrombotic or hemorrhagic disorders, or any other serious medical disorder not controlled in the investigator's judgment patient with
• Patients with a history of gastrointestinal perforation or fistula within 6 months.
• Concomitant diagnosis of cancer in another site or history of active malignant tumor within the past 3 years
• Excluding fully cured basal cell carcinoma and thyroid cancer, in situ cervical cancer

Sponsors & Collaborators

• Kangbuk Samsung Hospital: lead

Study Sites (1)

Kangbuk Samsung Hospital

Seoul, 110-746, South Korea

RECRUITING

Related Publications (11)

• Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S, Miyazaki I, Endou Y, Tanaka M, Sasaki T. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res. 1991 Feb 1;51(3):1034-8.

  PMID: 1670998 BACKGROUND

• Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19.

  PMID: 20728210 BACKGROUND

• Guideline Committee of the Korean Gastric Cancer Association (KGCA), Development Working Group & Review Panel. Korean Practice Guideline for Gastric Cancer 2018: an Evidence-based, Multi-disciplinary Approach. J Gastric Cancer. 2019 Mar;19(1):1-48. doi: 10.5230/jgc.2019.19.e8. Epub 2019 Mar 19. No abstract available.

  PMID: 30944757 BACKGROUND

• Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. doi: 10.1056/NEJMoa2004413. Epub 2020 May 29.

  PMID: 32469182 BACKGROUND

• du Manoir JM, Francia G, Man S, Mossoba M, Medin JA, Viloria-Petit A, Hicklin DJ, Emmenegger U, Kerbel RS. Strategies for delaying or treating in vivo acquired resistance to trastuzumab in human breast cancer xenografts. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):904-16. doi: 10.1158/1078-0432.CCR-05-1109.

  PMID: 16467105 BACKGROUND

• Singh R, Kim WJ, Kim PH, Hong HJ. Combined blockade of HER2 and VEGF exerts greater growth inhibition of HER2-overexpressing gastric cancer xenografts than individual blockade. Exp Mol Med. 2013 Nov 1;45(11):e52. doi: 10.1038/emm.2013.111.

  PMID: 24176949 BACKGROUND

• 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.

  PMID: 24094768 BACKGROUND

• 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.

  PMID: 25240821 BACKGROUND

• Meulendijks D, Beerepoot LV, Boot H, de Groot JW, Los M, Boers JE, Vanhoutvin SA, Polee MB, Beeker A, Portielje JE, de Jong RS, Goey SH, Kuiper M, Sikorska K, Beijnen JH, Tesselaar ME, Schellens JH, Cats A. Trastuzumab and bevacizumab combined with docetaxel, oxaliplatin and capecitabine as first-line treatment of advanced HER2-positive gastric cancer: a multicenter phase II study. Invest New Drugs. 2016 Feb;34(1):119-28. doi: 10.1007/s10637-015-0309-4. Epub 2015 Dec 8.

  PMID: 26643663 BACKGROUND

• Jung M, Ryu MH, Oh DY, Kang M, Zang DY, Hwang IG, Lee KW, Kim KH, Shim BY, Song EK, Sym SJ, Han HS, Park YL, Kim JS, Lee HW, Lee MH, Koo DH, Song HS, Lee N, Yang SH, Choi DR, Hong YS, Lee KE, Maeng CH, Baek JH, Kim S, Kim YH, Rha SY, Cho JY, Kang YK. Efficacy and tolerability of ramucirumab monotherapy or in combination with paclitaxel in gastric cancer patients from the Expanded Access Program Cohort by the Korean Cancer Study Group (KCSG). Gastric Cancer. 2018 Sep;21(5):819-830. doi: 10.1007/s10120-018-0806-1. Epub 2018 Feb 9.

  PMID: 29427038 BACKGROUND

• Mun DG, Bhin J, Kim S, Kim H, Jung JH, Jung Y, Jang YE, Park JM, Kim H, Jung Y, Lee H, Bae J, Back S, Kim SJ, Kim J, Park H, Li H, Hwang KB, Park YS, Yook JH, Kim BS, Kwon SY, Ryu SW, Park DY, Jeon TY, Kim DH, Lee JH, Han SU, Song KS, Park D, Park JW, Rodriguez H, Kim J, Lee H, Kim KP, Yang EG, Kim HK, Paek E, Lee S, Lee SW, Hwang D. Proteogenomic Characterization of Human Early-Onset Gastric Cancer. Cancer Cell. 2019 Jan 14;35(1):111-124.e10. doi: 10.1016/j.ccell.2018.12.003.

  PMID: 30645970 BACKGROUND

MeSH Terms

Interventions

Trastuzumab; Bevacizumab; Paclitaxel

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Dong-Hoe Koo, MD,PhD

  Kangbuk Samsung Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dong-Hoe Koo, MD,PhD

CONTACT

+82-2-2001-8330; dhkoo.smc@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 25, 2022
• First Posted: December 7, 2022
• Study Start: January 1, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 26, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)