Docetaxel Versus Docetaxel Plus Cisplatin Versus Docetaxel Plus S-1 as Second-line Chemotherapy in Metastatic Gastric Cancer

Sponsor

National Cancer Center, Korea (Other)

Overall Status

Unknown status

CT.gov ID

NCT00980603

Collaborator

Seoul National University Bundang Hospital (Other), Chungbuk National University Hospital (Other), Gachon University Gil Medical Center (Other)

144

Enrollment

Locations

Arms

29.9

Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess efficacy and safety of docetaxel alone, docetaxel plus cisplatin, and docetaxel plus S-1 in patients with metastatic gastric cancer after failing 1st line chemotherapy with cisplatin plus S-1 or capecitabine

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Drug: docetaxel Drug: docetaxel, cisplatin Drug: docetaxel, S-1	Phase 2

Detailed Description

To date, the most commonly used first-line chemotherapies have been based on fluorouracil and/or cisplatin in patients with metastatic gastric cancer. Unfortunately, considerable proportions of patients with metastatic gastric cancer do not respond to first-line chemotherapy and most of the patients who do respond eventually experience disease progression. In the second-line treatment, however, standard therapies are less clearly defined.

Meanwhile, regarding re-challenge of previous failed drugs as a combination with an other newly introduced chemotherapeutic agent, there are few data. Increased expression and activity of thymidylate synthase, which is inhibited by fluoropyrimidine, is regarded to be the main reason for the development of clinical resistance to fluoropyrimidine. Since the cotreatment of docetaxel and 5-fluorouracil decreases the activity and expression of thymidylate synthase and dihydropyrimidine dehydrogenase (5-fluorouracil degradation enzyme), and increases the expression of orotate phosphoribosyl transferase, the addition of docetaxel into S-1 may recover the sensitivity to S-1 in patients previously resistant to S-1.

Several reports found that MDR-1 and MRP-1 are related to cisplatin-resistance; cisplatin induces the overexpression of MRP-1, which reduces intracellular cisplatin accumulation. Since docetaxel suppresses the cisplatin-induced MRP-1 upregulation, the addition of docetaxel into cisplatin may recover the sensitivity to cisplatin in patients previously resistant to cisplatin.

Based on these synergism mechanisms, we speculate that the cotreatment of docetaxel and cisplatin or S-1 has better anti-tumor activity than docetaxel alone in patients resistant to cisplatin or S-1.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Study of Docetaxel vs. Docetaxel Plus Cisplatin vs. Docetaxel Plus S-1 as Second-line Chemotherapy After Cisplatin Plus S-1 or Capecitabine in Metastatic Gastric Cancer

Study Start Date :

Nov 1, 2008

Anticipated Primary Completion Date :

Nov 1, 2010

Anticipated Study Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: docetaxel	Drug: docetaxel docetaxel 75 mg/m2, IV on day 1 of each 3 week cycle until progression or unacceptable toxicity develops
Experimental: doctaxel plus cisplatin	Drug: docetaxel, cisplatin docetaxel 60 mg/m2 and cisplatin 60 mg/m2, IV on day 1 of each 3 week cycle until progression or unacceptable toxicity develops
Experimental: docetaxel plus S-1	Drug: docetaxel, S-1 docetaxel 60 mg/m2 IV on day 1 and S-1 30 mg/m2 bid PO on days 1-14 of each 3 week cycle until progression or unacceptable toxicity develops

Arm

Intervention/Treatment

Active Comparator: docetaxel

Drug: docetaxel

docetaxel 75 mg/m2, IV on day 1 of each 3 week cycle until progression or unacceptable toxicity develops

Experimental: doctaxel plus cisplatin

Drug: docetaxel, cisplatin

docetaxel 60 mg/m2 and cisplatin 60 mg/m2, IV on day 1 of each 3 week cycle until progression or unacceptable toxicity develops

Experimental: docetaxel plus S-1

Drug: docetaxel, S-1

docetaxel 60 mg/m2 IV on day 1 and S-1 30 mg/m2 bid PO on days 1-14 of each 3 week cycle until progression or unacceptable toxicity develops

Outcome Measures

Primary Outcome Measures

response rate [every 2 cycles]

Secondary Outcome Measures

time to progression [every 2 cycles]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed gastric adenocarcinoma with metastatic disease
Age ≥18 years
Eastern Cooperative Oncology Group performance status 0-2
At least one measurable lesion as defined by RECIST
Only one prior chemotherapy containing both S-1 or capecitabine and cisplatin for metastatic gastric cancer with documented progression of disease occurring during chemotherapy or within 6 months of completion of chemotherapy
Adequate major organ function:

ANC ≥1,500/mm3, Platelet ≥100,000/mm3, serum bilirubin ≤1.5 x upper limit of normal (ULN), AST/ALT ≤2.5 x ULN (≤5 x ULN if liver metastases are present), creatinine clearance ≥50 ml/min using the calculation formula or 24 hours urine collection

Patients should sign a written informed consent before study entry

Exclusion Criteria:

Prior taxane treatment
Major surgery or radiotherapy less than 4 weeks prior to entry
NCI CTCAE (version 3.0) adverse events ≥grade 2 except alopecia, fatigue, and weight loss
Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome, or inability to take oral medication
Patients with active gastrointestinal bleeding
Inadequate cardiovascular function
Serious concurrent infection or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy
Other malignancy within the past 3 years except adequately treated non-melanomatous skin cancer, carcinoma in situ of the cervix, or in situ of prostate cancer Gleason≤7
Psychiatric disorder that would preclude compliance
Patients receiving a concomitant treatment with drugs interacting with S-1 such as flucytosine, phenytoin, or allopurinol
Female patients who are pregnant or breast feeding or adults of reproductive potential not employing effective method of birth control

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Chungbuk National University Hospital	Chonju	Korea, Republic of	361-711
2	Research Institute and Hospital, National Cancer Center Korea	Goyang	Korea, Republic of	410-769
3	Gachon University Gil Hospital	Inchon	Korea, Republic of	405-760
4	Seoul National University Bundang Hospital	Seongnam	Korea, Republic of	463-707