Trastuzumab to Patients With Advanced Gastric Cancer With HER2 Positive Expression in CTC

NCT04168931 | Terminated Phase 2

• 1 other identifier: 2793/19
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

BACKGROUND: Gastric cancer is one of the most common cancers and is one of the most deadly cancers. Most patients have advanced disease and should receive first-line trastuzumab-associated chemotherapy when the biopsy is positive for immunocytochemical expression and / or HER2 gene amplification. A study conducted by our group noted that there may be disagreement in HER2 expression between circulating tumor cells (CTCs) and tumor tissue. However, the effectiveness of using anti-HER2 treatment when only CTC express HER2 is unknown. The present study aims to evaluate the expression of HER2 in patients with relapsed or metastatic gastric cancer and what would be the efficacy of adding trastuzumab to chemotherapy when tumor tissue is negative for HER2, but there is expression of this gene in CTCs. OBJECTIVES: The primary objectives are to evaluate HER2 expression in circulating tumor cells of relapsed or metastatic gastric cancer patients with negative HER2 expression on tissue biopsy and response to standard treatment with combined anti-HER2 chemotherapy in this population. Secondary objectives are to assess the prognostic impact of HER2 positivity on circulating tumor cells in advanced gastric tumors and to evaluate HER2 expression in CTCs at the time of treatment progression. METHODS: The investigators will prospectively evaluate HER2 expression in CTC and its response to treatment with standard chemotherapy and addition of trastuzumab in patients with relapsed or metastatic gastric cancer with positive expression of HER2 only in CTC. HER2 expression in tissue and in CTC will be evaluated by immunocytochemistry. Descriptive statistics will be used to report the results of categorical and continuous variables, and respective dispersion measures. Time-to-event variables will be reported in Kaplan Meyer medians and curves. EXPECTED RESULTS: Upon completion of the study the investigators expect to show the frequency of HER2 expression in this specific population, higher radiological response rate with trastuzumab combination compared to chemotherapy alone, determine the prognostic impact associated with HER2 expression in CTCs and show the frequency of HER2 expression in CTCs at the time of study treatment progression. This study may open a new opportunity for anti-HER2 treatment for gastric cancer patients.

Conditions

Gastric Cancer Stage IV

Keywords

gastric cancer; HER2; trastuzumab; circulating tumor cells

Outcome Measures

Primary Outcomes (3)

• Radiological response rate

  RECIST1.1 radiological response rate following standard treatment with combined chemotherapy with trastuzumab in relapsed or metastatic gastric cancer with positive expression of HER2 in CTC and negative in tumor tissue.

  through study completion, an average of 5 years

• Frequency of HER2 expression

  Frequency of HER2 expression among circulating tumor cells of patients with relapsed or metastatic gastric cancer with negative expression of HER2 in tumor tissue

  at screening before Day 1 Cycle 1 (each cycle is 14 days)

• Frequency of HER2 expression

  Frequency of HER2 expression among circulating tumor cells of patients with relapsed or metastatic gastric cancer with negative expression of HER2 in tumor tissue

  From date of randomization until the date of first documented progression, assessed up to 60 months

Study Arms (1)

Interventional

EXPERIMENTAL

Use of trastuzumab combination chemotherapy in patients with relapsed or metastatic gastric cancer with expression HER2 negative in the tumor tissue but positive in CTC.

Drug: Trastuzumab

Interventions

Trastuzumab DRUG

The first-line standard treatment for gastric cancer is based on fluoropyrimidine and platinum-containing chemotherapy (FOLFOX). When the tumor expresses HER2 3+ on IHC or 2+ and is confirmed by FISH, trastuzumab at the standard dose of 8 mg / kg in D1 of the first cycle is added, followed by 6 mg / kg every 2 weeks for the remaining cycles until disease progression, unacceptable toxicity. (3) We will use the same doses of trastuzumab, but HER2 positivity is determined by immunocytochemical expression and FISH in CTCs for patients with negative expression in tissue biopsy.

Also known as: Experimental group

Interventional

Eligibility Criteria

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

You may qualify if:

• Age 18 or over
• Histological diagnosis of recurrent or metastatic gastric cancer
• Immunohistochemistry (IHC 0 or 1+) or FISH negative (if IHQ 2+) for HER2 on tissue biopsy, according to institutional routine
• Candidates to initiate first-line palliative treatment; Previous adjuvant treatment is allowed since its termination occurred at least 12 months ago
• ECOG performance range 0 to 2
• Informed consent form signed by patient or legal representative

You may not qualify if:

• Patients already on or previously using anti-HER2 therapy
• Left ventricular ejection fraction (LVEF) \<55% baseline, as already evaluated in the gastric cancer routine
• Pregnant or lactating women
• Patients participating in other experimental drug protocols
• Patients who received previous palliative chemotherapy
• Another synchronic neoplasia requiring systemic treatment

Sponsors & Collaborators

• AC Camargo Cancer Center: lead

Study Sites (1)

AC Camargo Cancer Center

São Paulo, São Paulo, 01509-010, Brazil

Location

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MeSH Terms

Conditions

Stomach Neoplasms; Neoplastic Cells, Circulating

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rachel SP Riechelmann, PhD

  Head of Clinical Oncology Department

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Clinical Oncology Department

Model Details: This is a single-phase prospective unicentric phase II study evaluating HER2 expression in circulating tumor cells and their response to standard treatment with trastuzumab combination chemotherapy in cases of positive expression in patients with relapsed or metastatic gastric cancer with expression HER2 negative in the tumor tissue.

Study Record Dates

• First Submitted: November 5, 2019
• First Posted: November 19, 2019
• Study Start: January 1, 2020
• Primary Completion: January 13, 2023
• Study Completion: January 13, 2023
• Last Updated: January 17, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)