Gastric CancerPhase 2NCT00674167
The Effect of Preoperative Docetaxel, Cisplatin and Capecitabine on Serum RUNX3 Hypermethylation Status in Patients With Gastric and Lower Oesophagus Adenocarcinoma
A Phase 2 study testing Docetaxel, Cisplatin and Capecitabine in people with Gastric Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
To assess the radiological response, curative resection rate of preoperative docetaxel/cisplatin/capecitabine(DCX). To correlate treatment response with serum RUNX3 promoter hypermethylation. To determine the toxicities of preoperative DCX To determine the time to progression/overall survival of preoperative DCX Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Cancer
- What is being tested?
- Docetaxel, Cisplatin and Capecitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteSingapore
- Study dates
- May 2007to Dec 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
- Patients must have histologically or cytologically confirmed adenocarcinoma of the stomach or lower third of the oesophagusthat considered to be stage II (through the submucosa) or higher, with no evidence of distant metastases, or locally advanced inoperable disease, as evaluated by computed tomography, chest radiography, ultrasonography, or laparoscopy.
- Patients must have evaluable or measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan.
- Age >= 18 years. Because no dosing or adverse event data are currently available on the use of DCX in patients <18 years of age, children are excluded from this study.
- ECOG performance status <= 1 (see Appendix A).
- Patients must have normal organ and marrow function as defined below:
- X leukocytes >= 3,000/mcL X absolute neutrophil count >= 1,500/mcL X platelets >= 100,000/mcL X total bilirubin within normal institutional limits X AST(SGOT)/ALT(SGPT) <= 2.5 X institutional upper limit of normal X creatinine within normal institutional limits
- The effects of DCX on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had prior chemotherapy or radiotherapy.
- Patients may not be receiving any other investigational agents.
- Patients with stage I or IV cancer of the stomach or lower oesophagus.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetacel, cisplatin or capecitabine.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because agents use in the study may cause fetal harm.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with docetaxel. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Preoperative Docetaxel, Cisplatin and Capecitabine on Serum RUNX3 Hypermethylation Status in Patients With Gastric and Lower Oesophagus Adenocarcinoma.
- To assess the radiological response, curative resection rate of preoperative docetaxel/cisplatin/capecitabine(DCX).
- To correlate treatment response with serum RUNX3 promoter hypermethylation.
- To determine the toxicities of preoperative DCX
- To determine the time to progression/overall survival of preoperative DCX
Read the detailed description
Background:
Pre-operative chemotherapy down size and down stage tumours prior to surgery and improves treatment outcome. However, current chemotherapy regime requires long terrn venous access for protracted chemotherapy infusion. Despite encouraging response rate, there are still a substantial number who did not achieve curative resection after pre-operative chemotherapy. Hence there is a need to develop 1) a more convenient and effective regimen and 2) a surrogate for treatment response so that the non-responder can be identified early.
Specific aims:
To assess the radiological response, curative resection rate of preoperative docetaxel/cisplatin and capecitabine in patients with Stage II \& III gastric or lower oesophageal adenocarcinoma and to correlate treatment response with serum RUNX3 methylation status.
Hypotheses:
We hypothesize that the proposed preoperative regimen is effective in gastric cancer and can be safely delivered. In addition, RUNX3 promoter hypermethylation status can be a surrogate for treatment response.
Methodology:
This is a phase II study design to assess the response and tolerability of preoperative docetaxel, cisplatin and capecitabine in patients with operable gastric cancer. Simon's two-stage design is used to calculate the sample size for this Phase II trial, using two levels of response rate, P0 (20%) and P1 (50%). Accordingly, 20 patients is required for this study; 8 patients will be accrued for the first stage followed by 12 more patients when three or more responses are observed during the first stage. The alpha level of the design is 0.04 and power is 0.86. Serum measurement of tumour's RUNX3 promoter hypermethylation will be performed prior to each treatment cycle to evaluate its role as a biomarker for treatment response.
- Conditions
- Gastric Cancer
- Being tested
- Docetaxel, Cisplatin, Capecitabine
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Three cycles of chemotherapy will be administered before surgery with docetaxel at 30 mg/m² on day 1 and 8 in a 21 day treatment cycles.
CisplatinDrug
Three cycles of chemotherapy will be administered before surgery with cisplatin at 30 mg/m² on day 1 and 8 in a 21 day treatment cycle.
CapecitabineDrug
Three cycles of chemotherapy will be administered before surgery with capecitabine at 750 mg/m² twice daily from day 1 to 14 in a 21 day treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| Docetaxel | Experimental | Three cycles of chemotherapy will be administered before surgery with docetaxel and cisplatin at 30 mg/m² on day 1 and 8 in a 21 day treatment cycles. Receives: Drug: Docetaxel |
| Cisplatin | Experimental | Three cycles of chemotherapy will be administered before surgery with cisplatin at 30 mg/m² on day 1 and 8 in a 21 day treatment cycle. Receives: Drug: Cisplatin |
| Capecitabine | Experimental | Three cycles of chemotherapy will be administered before surgery with capecitabine at 750 mg/m² twice daily from day 1 to 14 in a 21 day treatment cycles. Receives: Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of Response and Progression using RECIST Criteria
Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques (CT, MRI, x-ray) or as >10 mm with spiral CT scan.
Measured: baseline and after two cycles of chemotherapy
Secondary outcomes (1)
Detection of methylated and unmethylated DNA
Treated DNA will be used for PCR using the appropriate primers. Primer sets for RUNX3 will be used for detecting methylated and unmethylated DNA. Results of methylation studies will be analysed and correlated with clinical parameters including age distribution, gender, age, staging, and treatment response. Additional genotyping may be performed on relevant polymorphisms such as XRCC, TS and CYP3A4 to correlate with treatment response.
Measured: before and after pre-operative chemotherapy (6-8 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2008 (estimated)
- Study startMay 2007
- Primary completionDec 2015 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gastric CancerStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Haematology-Oncology, National University Hospital, Singapore
- Investigators
- Wei Peng Yong, MRCP, MB ChB, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00674167
- Sponsor's protocol ID
- GA02/33/06
- Other IDs
- 2006/00462, CTC0700084
- Status last verified
- Jun 2015
- First submitted
- 5 May 2008
- Last updated
- 12 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. doi: 10.1056/NEJMoa055531.
PubMed 16822992Cassidy J, Twelves C, Van Cutsem E, Hoff P, Bajetta E, Boyer M, Bugat R, Burger U, Garin A, Graeven U, McKendric J, Maroun J, Marshall J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schilsky RL; Capecitabine Colorectal Cancer Study Group. First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol. 2002 Apr;13(4):566-75. doi: 10.1093/annonc/mdf089.
PubMed 12056707
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Preoperative Docetaxel, Cisplatin and Capecitabine on Serum RUNX3 Hypermethylation Status in Patients With Gastric and Lower Oesophagus Adenocarcinoma.
- ClinicalTrials.gov ID
- NCT00674167
- Acronym / sponsor ID
- GA02/33/06
- Conditions
- Gastric Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- May 2007
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 7 May 2008 (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.
- To assess the radiological response, curative resection rate of preoperative docetaxel/cisplatin/capecitabine(DCX).
- To correlate treatment response with serum RUNX3 promoter hypermethylation.
- To determine the toxicities of preoperative DCX
- To determine the time to progression/overall survival of preoperative DCX
Detailed description
Background:
Pre-operative chemotherapy down size and down stage tumours prior to surgery and improves treatment outcome. However, current chemotherapy regime requires long terrn venous access for protracted chemotherapy infusion. Despite encouraging response rate, there are still a substantial number who did not achieve curative resection after pre-operative chemotherapy. Hence there is a need to develop 1) a more convenient and effective regimen and 2) a surrogate for treatment response so that the non-responder can be identified early.
Specific aims:
To assess the radiological response, curative resection rate of preoperative docetaxel/cisplatin and capecitabine in patients with Stage II \& III gastric or lower oesophageal adenocarcinoma and to correlate treatment response with serum RUNX3 methylation status.
Hypotheses:
We hypothesize that the proposed preoperative regimen is effective in gastric cancer and can be safely delivered. In addition, RUNX3 promoter hypermethylation status can be a surrogate for treatment response.
Methodology:
This is a phase II study design to assess the response and tolerability of preoperative docetaxel, cisplatin and capecitabine in patients with operable gastric cancer. Simon's two-stage design is used to calculate the sample size for this Phase II trial, using two levels of response rate, P0 (20%) and P1 (50%). Accordingly, 20 patients is required for this study; 8 patients will be accrued for the first stage followed by 12 more patients when three or more responses are observed during the first stage. The alpha level of the design is 0.04 and power is 0.86. Serum measurement of tumour's RUNX3 promoter hypermethylation will be performed prior to each treatment cycle to evaluate its role as a biomarker for treatment response.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Docetaxel | Experimental | Drug: DocetaxelThree cycles of chemotherapy will be administered before surgery with docetaxel and cisplatin at 30 mg/m² on day 1 and 8 in a 21 day treatment cycles. |
| Cisplatin | Experimental | Drug: CisplatinThree cycles of chemotherapy will be administered before surgery with cisplatin at 30 mg/m² on day 1 and 8 in a 21 day treatment cycle. |
| Capecitabine | Experimental | Drug: CapecitabineThree cycles of chemotherapy will be administered before surgery with capecitabine at 750 mg/m² twice daily from day 1 to 14 in a 21 day treatment cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must have histologically or cytologically confirmed adenocarcinoma of the stomach or lower third of the oesophagusthat considered to be stage II (through the submucosa) or higher, with no evidence of distant metastases, or locally advanced inoperable disease, as evaluated by computed tomography, chest radiography, ultrasonography, or laparoscopy.
- Patients must have evaluable or measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan.
- Age >= 18 years. Because no dosing or adverse event data are currently available on the use of DCX in patients <18 years of age, children are excluded from this study.
- ECOG performance status <= 1 (see Appendix A).
- Patients must have normal organ and marrow function as defined below:
Key exclusion criteria (7 listed)
- Patients who have had prior chemotherapy or radiotherapy.
- Patients may not be receiving any other investigational agents.
- Patients with stage I or IV cancer of the stomach or lower oesophagus.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetacel, cisplatin or capecitabine.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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 |
|---|---|---|
| DocetaxelThree cycles of chemotherapy will be administered before surgery with docetaxel at 30 mg/m² on day 1 and 8 in a 21 day treatment cycles. | Drug | Docetaxel |
| CisplatinThree cycles of chemotherapy will be administered before surgery with cisplatin at 30 mg/m² on day 1 and 8 in a 21 day treatment cycle. | Drug | Cisplatin |
| CapecitabineThree cycles of chemotherapy will be administered before surgery with capecitabine at 750 mg/m² twice daily from day 1 to 14 in a 21 day treatment cycle. | Drug | Capecitabine |
Primary outcome
Evaluation of Response and Progression using RECIST Criteria
Time frame: baseline and after two cycles of chemotherapy
Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques (CT, MRI, x-ray) or as >10 mm with spiral CT scan.
1 secondary outcome
Detection of methylated and unmethylated DNA
Time frame: before and after pre-operative chemotherapy (6-8 weeks)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2015.
- Background: PubMed 16822992Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. doi: 10.1056/NEJMoa055531.
- Background: PubMed 12056707Cassidy J, Twelves C, Van Cutsem E, Hoff P, Bajetta E, Boyer M, Bugat R, Burger U, Garin A, Graeven U, McKendric J, Maroun J, Marshall J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schilsky RL; Capecitabine Colorectal Cancer Study Group. First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol. 2002 Apr;13(4):566-75. doi: 10.1093/annonc/mdf089.
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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.
Wei Peng Yong, MRCP, MB ChB principal investigator
National University Hospital, Singapore
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 Docetaxel, Cisplatin and Capecitabine in people with Gastric Cancer, run by National University Hospital, Singapore at 1 site in Singapore.
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 8 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: status not confirmed, as of the sponsor's last update on 12 Jun 2015. 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 Singapore. 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?
Results are not available in the source record.
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?
Evaluation of Response and Progression using RECIST Criteria (time frame: baseline and after two cycles of chemotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00674167, which also lists 2 linked publications.
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 12 Jun 2015.