The Effect of Preoperative Docetaxel, Cisplatin and Capecitabine on Serum RUNX3 Hypermethylation Status in Patients With Gastric and Lower Oesophagus Adenocarcinoma

NCT ID: NCT00674167

Last Updated: 2015-06-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2017-12-31

Brief 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

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Docetaxel

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

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.

Cisplatin

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.

Group Type: EXPERIMENTAL

Cisplatin

Intervention Type: DRUG

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.

Capecitabine

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.

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

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.

Interventions

Docetaxel

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.

Intervention Type: DRUG

Cisplatin

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.

Intervention Type: DRUG

Capecitabine

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

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

Sponsors

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Haematology-Oncology

Dr. Yong Wei Peng

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wei Peng Yong, MRCP, MB ChB

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Locations

National University Hospital

Singapore, , Singapore

Countries

Singapore

References

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.

Reference Type: BACKGROUND

PMID: 16822992 (View on PubMed)

Cassidy 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.

Reference Type: BACKGROUND

PMID: 12056707 (View on PubMed)

Other Identifiers

2006/00462

Identifier Type: OTHER

Identifier Source: secondary_id

CTC0700084

Identifier Type: OTHER

Identifier Source: secondary_id

GA02/33/06

Identifier Type: -

Identifier Source: org_study_id