Paclitaxel and Irinotecan in Advanced Gastric Cancer (TI-2ndAGC)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2010 by Seoul National University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01136031
First received: May 31, 2010
Last updated: NA
Last verified: May 2010
History: No changes posted
  Purpose
  • 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) in advanced gastric cancer.
  • 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.
  • 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.

Condition Intervention Phase
Advanced Gastric Cancer
Drug: Paclitaxel and irinotecan
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Second-line Chemotherapy With Paclitaxel and Irinotecan in Fluoropyrimidine- and Platinum-Pretreated Advanced Gastric Cancer

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • Dose-limiting toxicity (phase I part) [ Time Frame: during first cycle (first 3 week) ] [ Designated as safety issue: Yes ]
  • response rate (phase II part) [ Time Frame: every 2 cycles response evaluation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • recommended phase II dose [ Time Frame: after the determining MTD ] [ Designated as safety issue: Yes ]
  • time to progression [ Time Frame: at the time of disease progression ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: at the time of death ] [ Designated as safety issue: No ]
  • toxicities [ Time Frame: every time of physical exam and laboratory evaluation ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 42
Study Start Date: January 2008
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paclitaxel and irinotecan Drug: Paclitaxel and irinotecan

In phase I part, Level Paclitaxel (mg/m²) Irinotecan (mg/m²)

  1. 100 100
  2. 100 120
  3. 135 120
  4. 135 160

every 3 week


Detailed Description:

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 studies.

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 weeks.

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 patients.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 resection
  • 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 surgery.
  • A patient who has participated in a clinical trial with other medications or therapy within 4 weeks prior to the initiation of the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01136031

Contacts
Contact: Do-Youn Oh, MD, PhD 82-2-2072-0701 ohdoyoun@snu.ac.kr

Locations
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Do-Youn Oh, MD, PhD    82-2-2072-0701    ohdoyoun@snu.ac.kr   
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Principal Investigator: Do-Youn Oh, MD, PhD Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Do-Youn Oh/Assistant professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01136031     History of Changes
Other Study ID Numbers: H-0703-042-201
Study First Received: May 31, 2010
Last Updated: May 31, 2010
Health Authority: Korea: Seoul National University Hospital

Keywords provided by Seoul National University Hospital:
advanced gastric cancer
1st-line failure

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Paclitaxel
Irinotecan
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 21, 2014