A Phase II Study of Sequential Capecitabine Plus Oxaliplatin (XELOX) Followed by Docetaxel Plus Capecitabine (TX) in Patients With Unresectable Gastric
20 Years
N/A
Both
Gastric Cancer
Trial Information
A Phase II Study of Sequential Capecitabine Plus Oxaliplatin (XELOX) Followed by Docetaxel Plus Capecitabine (TX) in Patients With Unresectable Gastric
Gastric cancer is one of the most frequent cancer types in Taiwan. Advanced gastric cancer
is incurable. Although chemotherapy can improve survival and maintain quality of life for
patients with advanced gastric cancer, optimal chemotherapy for this disease has not been
defined.
Cytotoxic agents commonly used in this disease include platinum compounds, fluoropyrimidines
and taxanes. A phase III (V325) study showed that adding docetaxel to cisplatin and 5-FU
(TCF) improved response rates, progression-free survival (PFS), and overall survival (OS).
Although the TCF regimen improved clinical outcomes, it was associated with substantial
toxicity particularly that related to myelosuppression, with a 29% incidence of febrile
neutropenia or neutropenic infection1. Several modifications to the TCF regimen have been
made to maintain efficacy and reduce toxicity.
Cunningham et al. evaluated the impact of substituting oxaliplatin for cisplatin and
capecitabine for 5-FU in the epirubicin, cisplatin, and 5-FU (ECF) regimen. Oxaliplatin as
compared with cisplatin demonstrated comparable efficacy, with a lower incidence of
myelosuppression, thromboembolic complications, and nephrotoxicity. The combination of
docetaxel and oxaliplatin has been evaluated in gastric cancer with moderate activities in
four phase II trials.
A different way of including all active agents in the first line treatment of advanced
gastric cancer is to use them sequentially. Sequential schedules may maximize the
dose-intensity of each single agent and avoid the overlapping toxicity caused by the
concomitant administration of active drugs. Two studies using sequential strategy to treat
advanced gastric cancer were reported.7-8 One used docetaxel after PELF regimen, the other
used cisplatin plus 5-Fluorouracil / leucovorin (5-FU/LV) followed by irinotecan plus
5-FU/LV, followed by docetaxel plus 5-FU/LV. Both studies shown that sequential approach
produced a good treatment efficacy with manageable toxicities in the management of advanced
gastric cancer.
In our hospital, we had completed two phase II studies in advanced gastric cancer, including
XELOX (capecitabine plus oxaliplatin) and a modified TCF regimen (docetaxel plus cisplatin
and oral tegafur/uracil plus leucovorin). After analyzing these results, the median time to
response, time to progression and overall survival were around 3, 6, and 10 months,
respectively. Overall response rate was around 50% for each.
Based on the above considerations and our previous experiences, we hence initiate this phase
II study to evaluate the feasibility and the anti-tumor activity of a new strategy consists
of two sequential regimens involving XELOX and TX in unresectable gastric cancer.
Inclusion Criteria:
- Pathologically confirmed gastric adenocarcinoma.
- At least one measurable lesion in a non-irradiated area.
- No prior exposure to systemic chemotherapy for advanced gastric cancer.
- For those have adjuvant chemotherapy after a curative gastrectomy, the last dosing of
previous adjuvant chemotherapy should be at least 6 months before the start of this
treatment.
- Aged > 20 years old.
- ECOG Performance Status <= 2.
- Life expectancy greater than 12 weeks.
- Adequate bone marrow function
- Adequate liver function
- Adequate renal function
Exclusion Criteria:
- Patient who are receiving concurrent radiotherapy, chemotherapy or other
experimental therapy. (Previous radiotherapy is allowable if the last dose was given
more than 1 month before the protocol treatment).
- Major surgery within two weeks prior to entering the study.
- Patients with CNS metastasis, including clinical suspicion.
- Patients who are under active or uncontrolled infections.
- Patients who had cardiac arrhythmia or myocardial infarction history 6 months before
entry.
- Patients with clinically detectable peripheral neuropathy > 2 on the CTC criteria
- Patients with concomitant illness that might be aggravated by chemotherapy.
- Patients who are pregnant or with breast feeding.
- Other concomitant or previously malignancy within 5 yrs except for in situ cervix
cancer or squamous cell carcinoma of the skin treated by surgery only.
- Patients with hypersensitivity to any component of the chemotherapeutic regimen.
- mental status is not fit for clinical trial
- can not take study medication orally
- fertile men and women unless using a reliable and appropriate contraceptive
method
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
objective tumor response rate
Outcome Description:
Analysis for the objective response rate will be conducted on both the intention-to-treat (ITT) and evaluable data sets. Response will be assessed by Response Evaluation Criteria in Solid Tumor (RECIST 1.1).The analysis will be in descriptive statistics, presented by point estimate and 95% confidence interval for the efficacy variable (Objective tumor response rate)
Outcome Time Frame:
2 year
Safety Issue:
No
Principal Investigator
Yee Chao, MD,PHD
Investigator Role:
Principal Investigator
Investigator Affiliation:
attending physician, cancer center, Taipei Veterans General Hospital
Authority:
Taiwan : Food and Drug Administration
Study ID:
DOH99-TD-C-111-007
NCT ID:
NCT01331928
Start Date:
January 2011
Completion Date:
Related Keywords:
- Gastric Cancer
- Sequential chemotherapy, gastric cancer
- Stomach Neoplasms
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