Docetaxel Versus Docetaxel Plus Cisplatin Versus Docetaxel Plus S-1 as Second-line Chemotherapy in Metastatic Gastric Cancer
Recruitment status was Recruiting
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Gastric Cancer |
Drug: docetaxel Drug: docetaxel, cisplatin Drug: docetaxel, S-1 |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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 |
- response rate [ Time Frame: every 2 cycles ] [ Designated as safety issue: No ]
- time to progression [ Time Frame: every 2 cycles ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 144 |
| Study Start Date: | November 2008 |
| Estimated Study Completion Date: | May 2011 |
| Estimated Primary Completion Date: | November 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| 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
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| Contact: Sook Ryun Park, Dr. | 82-31-920-1609 ext 1609 | sukryun73@hanmail.net |
| Contact: Young Lan Park, CRC | 82-31-920-0422 ext 0422 | lan0729@hanmail.net |
| Korea, Republic of | |
| Chungbuk National University Hospital | Recruiting |
| Chonju, Korea, Republic of, 361-711 | |
| Contact: Hye-Suk Han, M.D. sook3529@hanmail.net | |
| Sub-Investigator: Hye-Suk Han, M.D. | |
| Research Institute and Hospital, National Cancer Center Korea | Recruiting |
| Goyang, Korea, Republic of, 410-769 | |
| Contact: Sook Ryun Park, M.D. 82-31-920-1609 ext 1609 sukryun73@hanmail.net | |
| Contact: Young Lan Park, RN 82-31-920-0422 ext 0422 lan0729@hanmail.net | |
| Principal Investigator: Sook Ryun Park, M.D. | |
| Sub-Investigator: Noe Kyeong Kim, M.D., Ph.D. | |
| Sub-Investigator: Youngiee Park, M.D., Ph.D. | |
| Sub-Investigator: Byung-Ho Nam, Ph.D. | |
| Gachon University Gil Hospital | Not yet recruiting |
| Inchon, Korea, Republic of, 405-760 | |
| Contact: Dong Bok Shin, M.D., Ph.D. dbs@gilhospital.com | |
| Principal Investigator: Dong Bok Shin, M.D., Ph.D. | |
| Sub-Investigator: Sun Jin Sym, M.D. | |
| Seoul National University Bundang Hospital | Recruiting |
| Seongnam, Korea, Republic of, 463-707 | |
| Contact: Keun-Wook Lee, M.D., Ph.D. hmodoctor@hanmail.net | |
| Principal Investigator: Keun-Wook Lee, M.D., Ph.D. | |
| Principal Investigator: | Sook Ryun Park, Dr. | Research Institute and Hospital, National Cancer Center Korea |
More Information
No publications provided
| Responsible Party: | Sook Ryun Park/Dr., Research Institute and Hospital, National Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00980603 History of Changes |
| Other Study ID Numbers: | NCCCTS-07-296 |
| Study First Received: | September 18, 2009 |
| Last Updated: | September 18, 2009 |
| Health Authority: | Korea: Food and Drug Administration |
Keywords provided by National Cancer Center, Korea:
|
gastric cancer metastatic docetaxel cisplatin S-1 |
Additional relevant MeSH terms:
|
Stomach Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Stomach Diseases |
Docetaxel Cisplatin Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on June 17, 2013