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A Phase I/II Trial of Second-line Chemotherapy With Paclitaxel and Irinotecan in Fluoropyrimidine- and Platinum-Pretreated Advanced Gastric Cancer

Phase 1/Phase 2
18 Years
70 Years
Open (Enrolling)
Advanced Gastric Cancer

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Trial Information

A Phase I/II Trial of Second-line Chemotherapy With Paclitaxel and Irinotecan in Fluoropyrimidine- and Platinum-Pretreated Advanced Gastric Cancer

In gastric cancer, several active chemotherapeutic agents have been introduced.
Fluoropyrimidine, platinum, taxane and topoisomerase inhibitor are the most commonly used
agents. Many available single or combination regimens are existed. But, there is no standard
palliative chemotherapy regimen as a first line treatment in unresectable advanced gastric
cancer. Thereafter there is also no standard second line regimen.

Usually the combination of fluoropyrimidine with platinum is used as a first line
chemotherapy (for example, 5-FU+cisplatin, capecitabine+cisplatin, S-1+ cisplatin,
5-FU+oxaliplatin). After failure with this combination, taxane-based regimen or
irinotecan-based regimen is usually used. But, as a second-line regimen, the combination of
topoisomerase inhibitor with taxane has not been fully evaluated until now.

In some studies using docetaxel and irinotecan combination in gastric cancer, the toxicity
is highly concerned. (Jatoi A et al. 2002, Lordick F etl al. 2003, S Enrech et al. 2003,
Chang HM et al. 2003) The combination of paclitaxel and irinotecan in gastric cancer is
evaluated in two studies until now as far as we know (K Kobayashi et al. 2006, Hecht JR et
al. 2003). These are phase I/II design and used this combination as first or second line
treatment of gastric cancer. The response rate is 29.6% and 27% respectively. In one study,
grade 3,4 hematologic toxicity is 33.3%. The dosing schedule is different between these two

In one study, paclitaxel 50mg/m2 and irinotecan 50mg/m2 is used day 1and day 8 every 3
weeks. In the other study, paclitaxel 100mg/m2 and irinotecan 225mg/m2 is used every 3

In these studies, the state of UGT1A1 polymorphism of enrolled patients has not been
reported. Recently it is well known that the UGT1A1 polymorphism influences on the toxicity
profile of irinotecan, e,g. myelosuppression and diarrhea. If a patient with UGT1A1*28 (7/7
homozygosity) is included in the low level of phase I period, the MTD of irinotecan might be
set up in low dose without showing sufficient efficacy.

We think that it may be of deserve to evaluate the efficacy of paclitaxel and irinotecan
combination regimen in gastric cancer patients and it is necessary to conduct phase I study
to find out the accurate MTD of this regimen after considering the UGT1A1 polymorphism of

So we designed this phase I/II study to evaluate the efficacy and toxicity of second-line
chemotherapy with paclitaxel and irinotecan in fluoropyrimidine and platinum-pretreated
advanced gastric cancer.

Inclusion Criteria:

- Age 18 - 70 years

- A patient who is able to walk and should have ECOG performance status of 0-1.

- Histologically confirmed adenocarcinoma of the stomach

- Unresectable locally advanced or initially metastatic or recurrent after curative

- Prior one regimen chemotherapy including fluoropyrimidine and platinum. (FP, XP,
TS-1+cisplatin, FOLFOX)

- A patient with at least one measurable primary lesion of which the diameter is
confirmed to be 10mm in Spiral CT or multidetector CT (MD CT), or 20 mm or longer in
conventional CT (it should be used by a consistent method during the study period).

- A patient with the willingness to comply with the study protocol during the study
period and capable of complying with it.

- A patient who signed the informed consent prior to the participation of the study and
who understands that he/she has a right to withdrawal from participation in the study
at any time without any disadvantages.

Exclusion Criteria:

- A patient with no measurable disease

- A patient with previous chemotherapy without containing fluoropyrimidine or platinum.

- A patient with UGT1A1*28 allele ((TA)7/7 homozygosity)

- A patient with previous active or passive immunotherapy.

- A patient with intestinal obstruction or impending obstruction, recent active upper
GI bleeding

- A pregnant or lactating patient

- A patient of childbearing potential without being tested for pregnancy at baseline or
with being tested for positive. (A postmenopausal woman with the amenorrhea period of
at least 12 months or longer is considered to have non-childbearing potential.)

- A man or woman of childbearing potential who has no willingness to use a
contraceptive measure during the study.

- A patient with history of another malignant disease within past 5 years, except
curatively treated basal cell carcinoma of the skin and cervical carcinoma in situ
are excluded.

- A patient with history of uncontrolled seizures, central nervous system disorder or
psychiatric disorders that are considered clinically significant by the investigator
that would prohibit the understanding of informed consent or that may be considered
to interfere with the compliance of the administration of the study medications.

- A patient with clinically significant (i.e. active) heart disease (e.g. congestive
heart failure, symptomatic coronary artery diseases, cardiac arrhythmias, etc) or
myocardial infarction within past 12 months.

- A patient with interstitial pneumonia or diffused symptomatic fibrosis of the lungs.

- A patient with peripheral neuropathy of Grade 1 by NCI CTC, caused by other factors
(e.g. alcohol, diabetes, etc). If the absence of deep tendon reflexes (DTRs) is the
only neurologic disorder, this condition does not apply to the exclusion criteria.

- Organ allogenic transplantation requiring immunosuppressive therapy.

- A patient who developed uncontrolled serious infection or other uncontrolled serious
concomitant diseases.

- A patient with moderate or severe renal insufficiency or serum creatinine > 1.5 X
upper limit of normal].

- Adequate organ function

- A patient with hypersensitivity.

- A patient who has received major surgery within 4 weeks prior to the initiation of
the study or a patient who is not completely recovered from impact of the major

- A patient who has participated in a clinical trial with other medications or therapy
within 4 weeks prior to the initiation of the study.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity (phase I part)

Outcome Time Frame:

during first cycle (first 3 week)

Safety Issue:


Principal Investigator

Do-Youn Oh, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Seoul National University Hospital


Korea: Seoul National University Hospital

Study ID:




Start Date:

January 2008

Completion Date:

December 2011

Related Keywords:

  • Advanced Gastric Cancer
  • advanced gastric cancer
  • 1st-line failure
  • Stomach Neoplasms