Peritoneal Lavage Liquid Biopsy in Patients With Gastric Cancer

NCT ID: NCT04943406

Last Updated: 2023-10-06

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-05-08
• Study Completion Date: 2025-05-31

Brief Summary

This study investigates the prognostic role of liquid biopsy in patients with locally advanced gastric cancer.

Liquid biopsy for the detection of circulating tumor DNA will be performed:

• In the peritoneal lavage, during staging laparoscopy (if indicated) and during curative gastrectomy
• In plasma, before staging laparoscopy (if indicated), before curative gastrectomy, at hospital discharge, three months after surgery/at the end of adjuvant therapy, and in case of disease recurrence.

The aim of this study is to determine the predictive power of liquid biopsy on overall survival and disease free survival.

Detailed Description

The purpose of this prospective observational study is to determine the prognostic role of liquid biopsy for the detection of circulating tumor DNA (ctDNA) in patients with locally advanced gastric cancer.

Patients with cT3-4 and or N+ gastric cancer will proceed to either staging laparoscopy, if preoperative chemotherapy is indicated, or upfront radical surgery within 2 weeks from the last imaging assessment.

Liquid biopsy will be performed with peritoneal lavage and blood samples. Peritoneal lavage is performed with 500 ml of saline, starting from the retrogastric space (100 ml) and following clockwise from right upper quadrant to right lower using 100 ml for each quadrant. At the end of peritoneal lavage, 250 ml of saline solution is collected over the liver, after having positioned the patient in Trendelenburg position and on the right side. Of the collected fluid, 50 mL will be sent for cytological examination and 50 mL will be stocked for ctDNA analyses.

In case of upfront radical surgery, liquid biopsy will be performed at the following time points:

• Through blood samples performed before skin incision and 7-10 days after radical surgery;
• Through peritoneal lavage, immediately after laparotomy/laparoscopy.

In case of staging laparoscopy, liquid biopsy will be performed with blood samples, just before skin incision, and with peritoneal lavage. Patients with no evidence of peritoneal dissemination after staging laparoscopy will undergo induction chemotherapy according to the FLOT scheme or per investigators' judgment, and restaged after 4 cycles. Patients still fulfilling the inclusion criteria will undergo radical surgery within 3 weeks from the last chemotherapy cycle. Patients will then undergo liquid biopsy with the same scheme as for upfront radical surgery.

Patients who are clinically fit, and for whom there is clinical indication, will undergo adjuvant chemotherapy. Blood samples for ctDNA will be collected at the end of the last cycle of adjuvant chemotherapy, or at the end of the third postoperative month for those patients not undergoing postoperative chemotherapy. Then, patients will be followed up according to standard protocols by means of CT scan, CEA assessment and clinical visit every six months for the first three years after surgery and then yearly up to five years after local treatments. Blood samples for ctDNA will be collected at detection of cancer recurrence.

Conditions

Gastric Cancer; Gastric Adenocarcinoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Histologically proven gastric or gastro-esophageal junction (GEJ -Siewert type II -III) adenocarcinoma
• More than cT2 and/or N + (UICC 8th edition)
• Written informed consent

Exclusion Criteria

• Presence of ascites or distant metastases
• Previous chemotherapy for gastric adenocarcinoma
• Previous gastric surgery
• Absolute contraindications to surgery
• Concomitant malignancies or history of other malignancies in the previous 5 years (with exception of in situ cervical carcinoma, basal cell carcinoma, superficial bladder tumors are allowed if curatively treated).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Responsible Party

Carlo Sposito

Staff Surgeon

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carlo Sposito, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Locations

Fondazione IRCSS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Carlo Sposito, MD

Role: CONTACT

carlo.sposito@istitutotumori.it

02-2390-3496 ext. +39

Facility Contacts

Carlo Sposito, MD

Role: primary

carlo.sposito@istitutotumori.mi.it

02-2390-3496 ext. +39

References

Badgwell B, Cormier JN, Krishnan S, Yao J, Staerkel GA, Lupo PJ, Pisters PW, Feig B, Mansfield P. Does neoadjuvant treatment for gastric cancer patients with positive peritoneal cytology at staging laparoscopy improve survival? Ann Surg Oncol. 2008 Oct;15(10):2684-91. doi: 10.1245/s10434-008-0055-3. Epub 2008 Jul 23.

Reference Type: BACKGROUND

PMID: 18649106 (View on PubMed)

Allen CJ, Newhook TE, Vreeland TJ, Das P, Minsky BD, Blum M, Song S, Ajani J, Ikoma N, Mansfield PF, Roy-Chowdhuri S, Badgwell BD. Yield of peritoneal cytology in staging patients with gastric and gastroesophageal cancer. J Surg Oncol. 2019 Dec;120(8):1350-1357. doi: 10.1002/jso.25729. Epub 2019 Oct 14.

Reference Type: BACKGROUND

PMID: 31612494 (View on PubMed)

Rossi E, Bizzarro T, Martini M, Longatto-Filho A, Schmitt F, Fagotti A, Scambia G, Zannoni GF. The Role of Liquid Based Cytology and Ancillary Techniques in the Peritoneal Washing Analysis: Our Institutional Experience. PLoS One. 2017 Jan 18;12(1):e0168625. doi: 10.1371/journal.pone.0168625. eCollection 2017.

Reference Type: BACKGROUND

PMID: 28099523 (View on PubMed)

Takahashi H, Akita H, Wada H, Tomokuni A, Asukai K, Takahashi Y, Yanagimoto Y, Matsunaga T, Sugimura K, Yamamoto K, Nishimura J, Yasui M, Omori T, Miyata H, Yamamoto T, Nakanishi M, Shirayanagi M, Yamasaki T, Ohue M, Yano M, Sakon M, Ishikawa O. Subclinical cancer cell dissemination in peritoneal lavage fluid detected by reverse-transcription polymerase chain reaction identifies patients at high risk for peritoneal recurrence and consequent impaired survival in the setting of preoperative chemoradiation therapy for pancreatic cancer. Surgery. 2018 Dec;164(6):1168-1177. doi: 10.1016/j.surg.2018.06.047. Epub 2018 Aug 24.

Reference Type: BACKGROUND

PMID: 30146098 (View on PubMed)

Normanno N, Cervantes A, Ciardiello F, De Luca A, Pinto C. The liquid biopsy in the management of colorectal cancer patients: Current applications and future scenarios. Cancer Treat Rev. 2018 Nov;70:1-8. doi: 10.1016/j.ctrv.2018.07.007. Epub 2018 Jul 18.

Reference Type: BACKGROUND

PMID: 30053724 (View on PubMed)

Mok TS, Wu YL, Papadimitrakopoulou VA. Osimertinib in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 May 18;376(20):1993-4. doi: 10.1056/NEJMc1703339. No abstract available.

Reference Type: BACKGROUND

PMID: 28514610 (View on PubMed)

Barault L, Amatu A, Siravegna G, Ponzetti A, Moran S, Cassingena A, Mussolin B, Falcomata C, Binder AM, Cristiano C, Oddo D, Guarrera S, Cancelliere C, Bustreo S, Bencardino K, Maden S, Vanzati A, Zavattari P, Matullo G, Truini M, Grady WM, Racca P, Michels KB, Siena S, Esteller M, Bardelli A, Sartore-Bianchi A, Di Nicolantonio F. Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer. Gut. 2018 Nov;67(11):1995-2005. doi: 10.1136/gutjnl-2016-313372. Epub 2017 Oct 5.

Reference Type: BACKGROUND

PMID: 28982739 (View on PubMed)

Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA, Kinzler KW, Vogelstein B, Diaz LA Jr. Circulating mutant DNA to assess tumor dynamics. Nat Med. 2008 Sep;14(9):985-90. doi: 10.1038/nm.1789. Epub 2007 Jul 31.

Reference Type: BACKGROUND

PMID: 18670422 (View on PubMed)

Pantel K, Alix-Panabieres C. Liquid biopsy and minimal residual disease - latest advances and implications for cure. Nat Rev Clin Oncol. 2019 Jul;16(7):409-424. doi: 10.1038/s41571-019-0187-3.

Reference Type: BACKGROUND

PMID: 30796368 (View on PubMed)

Tie J, Cohen JD, Wang Y, Christie M, Simons K, Lee M, Wong R, Kosmider S, Ananda S, McKendrick J, Lee B, Cho JH, Faragher I, Jones IT, Ptak J, Schaeffer MJ, Silliman N, Dobbyn L, Li L, Tomasetti C, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer. JAMA Oncol. 2019 Dec 1;5(12):1710-1717. doi: 10.1001/jamaoncol.2019.3616.

Reference Type: BACKGROUND

PMID: 31621801 (View on PubMed)

Hamakawa T, Kukita Y, Kurokawa Y, Miyazaki Y, Takahashi T, Yamasaki M, Miyata H, Nakajima K, Taniguchi K, Takiguchi S, Mori M, Doki Y, Kato K. Monitoring gastric cancer progression with circulating tumour DNA. Br J Cancer. 2015 Jan 20;112(2):352-6. doi: 10.1038/bjc.2014.609. Epub 2014 Dec 9.

Reference Type: BACKGROUND

PMID: 25490524 (View on PubMed)

Fang WL, Lan YT, Huang KH, Liu CA, Hung YP, Lin CH, Jhang FY, Chang SC, Chen MH, Chao Y, Lin WC, Lo SS, Fen-Yau Li A, Wu CW, Chiou SH, Shyr YM. Clinical significance of circulating plasma DNA in gastric cancer. Int J Cancer. 2016 Jun 15;138(12):2974-83. doi: 10.1002/ijc.30018. Epub 2016 Feb 18.

Reference Type: BACKGROUND

PMID: 26815009 (View on PubMed)

Gao Y, Xi H, Wei B, Cui J, Zhang K, Li H, Cai A, Shen W, Li J, Rosell R, Chao J, Chen T, Klempner S, Qiao Z, Chen L. Association Between Liquid Biopsy and Prognosis of Gastric Cancer Patients: A Systematic Review and Meta-Analysis. Front Oncol. 2019 Nov 26;9:1222. doi: 10.3389/fonc.2019.01222. eCollection 2019.

Reference Type: BACKGROUND

PMID: 31850190 (View on PubMed)

Tsuchida K, Yoshikawa T, Tsuburaya A, Cho H, Kobayashi O. Indications for staging laparoscopy in clinical T4M0 gastric cancer. World J Surg. 2011 Dec;35(12):2703-9. doi: 10.1007/s00268-011-1290-5.

Reference Type: BACKGROUND

PMID: 21953130 (View on PubMed)

Other Identifiers

INT 55/20

Identifier Type: -

Identifier Source: org_study_id