HER2-positive Gastric Cancer Patients With Liver MetastasisPhase 2NCT02015169
Phase II Study of Neoadjuvant XELOX + Lapatinib in HER2(+) Gastric Cancer Patients With Liver Metastasis
A Phase 2 study testing Lapatinib in people with HER2-positive Gastric Cancer Patients With Liver Metastasis, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
We planned this study to investigate the efficacy and safety of XELOX (capecitabine and oxaliplatin) plus lapatinib treatment in HER2-positive gastric cancer patients with liver metastasis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2-positive Gastric Cancer Patients With Liver Metastasis
- What is being tested?
- Lapatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteSouth Korea
- Study dates
- 9 Jul 2012to 17 Nov 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven gastric cancer with metastatic lesion(s) that is (are) unresectable
- locally advanced gastric cancer that are NOT resectable
- distant metastases limited to abdominal lymph node, liver only :Patients with liver metastasis : Number of liver metastasis between 2 and 5 or maximal diameter should be under 5 cm (2 = liver mets = 5 or maximal diameter = 5cm) No LN metastasis within group 3 and no bulky N2 metastasis Clinically no distant metastasis (lung metastasis, mediastinal LN metastasis, neck LN metastasis, bone metastasis, brain metastasis, and peritoneal seeding in abdominal and pelvis CT; in cases of suspicious peritoneal seeding in imaging without any evidence of ascites and/or peritoneal enhancement will be allowed to enter the study based on investigators' decision)
- chemo-naïve (adjuvant treatment will be allowed if the last date of treatment is ≥ 6 months from the study entry date
- Age ≥ 18
- ECOG performance 0 - 1
Show all 10Show fewer
- Adequate organ function (AST and ALT ≤2x upper limit of normal, bilirubin ≤1.5 x upper limit of normal, and creatinine < 1.5x upper limit of normal, platelet > 100,000/ul, absolute neutrophil count ≥ 1,500/ul)
- At least one measurable lesion by RECIST 1.1 criteria
- HER 2 (+) by HercepTest(IHC 3+ alone, or IHC 2+ with FISH amplification)
- Written informed consent
Who cannot join
- Prior therapy for metastatic disease
- Pregnant or lactating women
- Uncontrolled medical illnesses including medically uncontrolled infection, uncontrolled hypertension, unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months
- Any comorbidities which are not suitable for general anesthesia and surgical resection
- Distant metastases other than liver or abdominal lymph nodes (As outlined in inclusion criteria, and peritoneal seeding in abdominal and pelvis CT; in cases of suspicious peritoneal seeding in imaging without any evidence of ascites and/or peritoneal enhancement will be allowed to enter the study based on investigators' decision)
- Known immediate or delayed hypersensitivity reaction to lapatinib ,capecitabine, oxaliplatin or any other platinum compounds, any recipients.
- 8) Subjects with DPD deficiency 9) Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) 10) Pre-existing hand and foot syndrome and peripheral neuropathy of grade 2 or greater 11) Subjects unsuitable to resection or general anesthesia
Trial locations and contacts
1 site in 1 country.
About this study
We planned this study to investigate the efficacy and safety of XELOX (capecitabine and oxaliplatin) plus lapatinib treatment in HER2-positive gastric cancer patients with liver metastasis.
Read the detailed description
Gastric cancer is the leading cause of cancer death worldwide with the incidence of 18.9/100,000 per year and the mortality rate of 14.7/100,000 per year [1] and is the most common malignancy in Korea[2]. Metastatic gastric cancer remains a therapeutic challenge for medical oncologists due to poor prognosis. Several randomized phase III trials comparing combination chemotherapy such as 5-fluorouracil (5-FU), doxorubicin, and mitomycin (FAM), or 5-FU, doxorubicin, and high-dose methotrexate (FAMTX) with best supportive care have demonstrated significantly prolonged overall survival (8 - 10 months) for chemotherapy group as compared to best supportive care alone (3 - 5 months)[3, 4].
In quest of a novel therapeutic target for gastric cancer, HER2 overexpression has been tested and was reported in 6-35% of stomach and gastroesophageal tumors [5]. Trastuzumab, a humanized monoclonal antibody which selectively targets HER2, has shown survival benefit in patients with HER2(+) metastatic breast cancer [6-8]. The ToGA trial is the first randomized, prospective, multicenter, phase III trial to study the efficacy and safety of trastuzumab in HER2(+) GC [9]. Of 3,807 tumor samples screened for Her2 status, 22.1% were Her2 positive and 594 patients were randomized to receive chemotherapy alone or chemotherapy + trastuzumab.
The ToGA trial demonstrated a significant survival benefit in the transtuzumab +chemotherapy when compared with chemotherapy alone arm: 13.5 vs. 11.1 months, respectively (p=0.0048; HR 0.74; 95% CI 0.60, 0.91). ORR was 47.3% in the trastuzumab + 5-FU/CDDP (or capecitabine/CDDP) arm and 34.5% in the chemotherapy alone arm (p=0.0017). The ToGA trial is the first phase III trial to demonstrate survival benefit from molecularly targeted agent in gastric cancer.
Of note, 70 - 80% of patients HER2 overexpressing breast cancer do not respond to trastuzumab due to either primary or acquired resistance. One of the important mechanisms for trastuzumab resistance is the accumulation of truncated forms of the HER2 receptor which lack the extracellular trastuzumab-binding domain (Figure 2). P95HER2, an amino terminally truncated carboxyl terminal fragments of HER2, is frequently found in HER2(+) breast cancer cell lines and tumor specimens (~20%)[11]. Intriguingly, recent study showed that p95HER2 (+) breast cancer cells were resistant to trastuzumab but remained sensitive to the antiproliferative effects of the tyrosine kinase inhibitor lapatinib, both in vitro and in vivo[11]. In addition, patients with p95HER2(+)breast cancer were resistant to trastuzumab with significantly lower response rate when compared with full-length HER2(+) breast cancer (11.1% vs 51.4%, respectively; P = 0.029).
We have surveyed the incidence of p95HER2 expression in fresh frozen tissues from gastric cancer and found that > 60% of HER2 (3+) GC demonstrated p95HER2. Hence, the role of lapatinib may be more promising than trastuzumab in GC HER2(+) patients with truncation.
- Being tested
- Lapatinib
- Keywords
- gastric cancer, neoadjuvant chemotherapy, capecitabine, oxaliplatin, lapatinib
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LapatinibDrug
Also called Tykerb, GSK
lapatinib 1250mg qd daily up to 8 cycles (3 weeks * 8 cycles = 24 weeks)
| Study group | Role | What they receive |
|---|---|---|
| XELOX+lapatinib | Experimental | D1 Oxaliplatin130mg/m2 + D5W 500ml MIV over 2hrs
D1-D14 Capecitabine 850mg/m2 p.o bid
D1 ~ Lapatinib 1250 mg qd dailiy Receives: Drug: Lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
complete resection rate (R0 resection rate) (defined as no macroscopic or microscopic residual tumor).
Measured: after surgery, up to 3weeks
Secondary outcomes (5)
response rate based on RECIST 1.1
Measured: every 3 cycles, up to 24weeks
disease-free survival
Measured: after surgery, every 3 months
progression-free survival
from date of study enrollment until the date of first documented progression or date of death from any cause, whichever came first
Measured: every 3 cycles for 6 months and ten every 3 months up to 3 years
safety and toxicity based on NCI CTCAE ver. 4.0
Number of participants with adverse events
Measured: every cycles, up to 24 weeks
Exploratory biomarker analysis
change in circulating tumor cells, HER2 positivity in primary and metastatic tumors, Receptor tyrosine kinase activation profiling including total HER1, HER2, HER3, phosphorylated HER1, HER2, HER3 - Prometheus, USA, Correlation between response rate and p95HER2 (truncated HER2)) Correlation between RR and RNA sequencing (all available tissue specimens)
Measured: every 3 cycles, up to 24weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2013 (estimated)
- Study start9 Jul 2012
- Primary completion17 Jul 2017
- Study completion17 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2-positive Gastric Cancer Patients With Liver MetastasisStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeeyun Lee, Samsung Medical Center
- Investigators
- Jeeyun Lee, MD, PhD, Principal investigator, Division of Oncology, Department of Medicine, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02015169
- Sponsor's protocol ID
- 2012-05-078
- Status last verified
- Jan 2018
- First submitted
- 17 Sep 2013
- Last updated
- 17 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Neoadjuvant XELOX + Lapatinib in HER2(+) Gastric Cancer Patients With Liver Metastasis
- ClinicalTrials.gov ID
- NCT02015169
- Acronym / sponsor ID
- 2012-05-078
- Keywords
- gastric cancer, neoadjuvant chemotherapy, capecitabine, oxaliplatin, lapatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- 9 Jul 2012 (actual)
- Primary completion
- 17 Jul 2017 (actual)
- Study completion
- 17 Nov 2017 (actual)
- First posted
- 19 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We planned this study to investigate the efficacy and safety of XELOX (capecitabine and oxaliplatin) plus lapatinib treatment in HER2-positive gastric cancer patients with liver metastasis.
Detailed description
Gastric cancer is the leading cause of cancer death worldwide with the incidence of 18.9/100,000 per year and the mortality rate of 14.7/100,000 per year [1] and is the most common malignancy in Korea[2]. Metastatic gastric cancer remains a therapeutic challenge for medical oncologists due to poor prognosis. Several randomized phase III trials comparing combination chemotherapy such as 5-fluorouracil (5-FU), doxorubicin, and mitomycin (FAM), or 5-FU, doxorubicin, and high-dose methotrexate (FAMTX) with best supportive care have demonstrated significantly prolonged overall survival (8 - 10 months) for chemotherapy group as compared to best supportive care alone (3 - 5 months)[3, 4].
In quest of a novel therapeutic target for gastric cancer, HER2 overexpression has been tested and was reported in 6-35% of stomach and gastroesophageal tumors [5]. Trastuzumab, a humanized monoclonal antibody which selectively targets HER2, has shown survival benefit in patients with HER2(+) metastatic breast cancer [6-8]. The ToGA trial is the first randomized, prospective, multicenter, phase III trial to study the efficacy and safety of trastuzumab in HER2(+) GC [9]. Of 3,807 tumor samples screened for Her2 status, 22.1% were Her2 positive and 594 patients were randomized to receive chemotherapy alone or chemotherapy + trastuzumab.
The ToGA trial demonstrated a significant survival benefit in the transtuzumab +chemotherapy when compared with chemotherapy alone arm: 13.5 vs. 11.1 months, respectively (p=0.0048; HR 0.74; 95% CI 0.60, 0.91). ORR was 47.3% in the trastuzumab + 5-FU/CDDP (or capecitabine/CDDP) arm and 34.5% in the chemotherapy alone arm (p=0.0017). The ToGA trial is the first phase III trial to demonstrate survival benefit from molecularly targeted agent in gastric cancer.
Of note, 70 - 80% of patients HER2 overexpressing breast cancer do not respond to trastuzumab due to either primary or acquired resistance. One of the important mechanisms for trastuzumab resistance is the accumulation of truncated forms of the HER2 receptor which lack the extracellular trastuzumab-binding domain (Figure 2). P95HER2, an amino terminally truncated carboxyl terminal fragments of HER2, is frequently found in HER2(+) breast cancer cell lines and tumor specimens (~20%)[11]. Intriguingly, recent study showed that p95HER2 (+) breast cancer cells were resistant to trastuzumab but remained sensitive to the antiproliferative effects of the tyrosine kinase inhibitor lapatinib, both in vitro and in vivo[11]. In addition, patients with p95HER2(+)breast cancer were resistant to trastuzumab with significantly lower response rate when compared with full-length HER2(+) breast cancer (11.1% vs 51.4%, respectively; P = 0.029).
We have surveyed the incidence of p95HER2 expression in fresh frozen tissues from gastric cancer and found that > 60% of HER2 (3+) GC demonstrated p95HER2. Hence, the role of lapatinib may be more promising than trastuzumab in GC HER2(+) patients with truncation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| XELOX+lapatinib | Experimental | Drug: LapatinibD1 Oxaliplatin130mg/m2 + D5W 500ml MIV over 2hrs D1-D14 Capecitabine 850mg/m2 p.o bid D1 ~ Lapatinib 1250 mg qd dailiy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically proven gastric cancer with metastatic lesion(s) that is (are) unresectable
- Age ≥ 18
- ECOG performance 0 - 1
- Adequate organ function (AST and ALT ≤2x upper limit of normal, bilirubin ≤1.5 x upper limit of normal, and creatinine < 1.5x upper limit of normal, platelet > 100,000/ul, absolute neutrophil count ≥ 1,500/ul)
- At least one measurable lesion by RECIST 1.1 criteria
Key exclusion criteria (7 listed)
- Prior therapy for metastatic disease
- Pregnant or lactating women
- Uncontrolled medical illnesses including medically uncontrolled infection, uncontrolled hypertension, unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months
- Any comorbidities which are not suitable for general anesthesia and surgical resection
- Distant metastases other than liver or abdominal lymph nodes (As outlined in inclusion criteria, and peritoneal seeding in abdominal and pelvis CT; in cases of suspicious peritoneal seeding in imaging without any evidence of ascites and/or peritoneal enhancement will be allowed to enter the study based on investigators' decision)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LapatinibAlso: Tykerb, GSKlapatinib 1250mg qd daily up to 8 cycles (3 weeks * 8 cycles = 24 weeks) | Drug | XELOX+lapatinib |
Primary outcome
complete resection rate (R0 resection rate) (defined as no macroscopic or microscopic residual tumor).
Time frame: after surgery, up to 3weeks
5 secondary outcomes
response rate based on RECIST 1.1
Time frame: every 3 cycles, up to 24weeks
disease-free survival
Time frame: after surgery, every 3 months
progression-free survival
Time frame: every 3 cycles for 6 months and ten every 3 months up to 3 years
safety and toxicity based on NCI CTCAE ver. 4.0
Time frame: every cycles, up to 24 weeks
Exploratory biomarker analysis
Time frame: every 3 cycles, up to 24weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeeyun Lee, MD, PhD principal investigator
Division of Oncology, Department of Medicine, Samsung Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lapatinib in people with HER2-positive Gastric Cancer Patients With Liver Metastasis, run by Samsung Medical Center at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
complete resection rate (R0 resection rate) (defined as no macroscopic or microscopic residual tumor). (time frame: after surgery, up to 3weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2018.