Study of PEP02, Irinotecan or Docetaxel in Gastric or Gastroesophageal Junction Adenocarcinoma

Sponsor

PharmaEngine (Industry)

Overall Status

Completed

CT.gov ID

NCT00813072

Collaborator

(none)

135

Enrollment

Locations

Arms

Duration (Months)

6.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess objective tumor response in the single agent treatment of PEP02, irinotecan, or docetaxel for locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasms Esophageal Neoplasms	Drug: PEP02 Drug: irinotecan Drug: docetaxel	Phase 2

Detailed Description

Palliative chemotherapy has been shown to improve survival compared with best supportive care alone in patients with unresectable or recurrent gastric cancer. There is no standard second-line chemotherapy for advanced gastric cancer and no randomized-controlled trial data suggest a benefit of second-line chemotherapy compared with supportive care alone. Response rates of second-line therapy in phase II trials are similar to those seen for other cancers that are more commonly retreated. Combination therapy may achieve higher response rates than single agents, however, the survival outcome are the same. In addition, data suggest that patients may obtain symptomatic benefits from second-line therapy. In comparison to the toxicity profile of single agent with combination regimen, patients are more tolerable to single agent therapy than combination.

Based on the previous clinical experience in second line chemotherapy of advanced gastric cancer, the single agent of PEP02, irinotecan and docetaxel are selected as the regimens for this randomized phase II study. The efficacy and toxicity outcome of the three-arm design will be a valuable reference for future combination therapy or phase III study design.

Study Design

Study Type:

Interventional

Actual Enrollment :

135 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Study of PEP02, Irinotecan or Docetaxel as a Second Line Therapy in Patients With Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Study Start Date :

Nov 1, 2007

Actual Primary Completion Date :

Jul 1, 2010

Actual Study Completion Date :

Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1. PEP02 liposome irinotecan	Drug: PEP02 120 mg/m2, IV infusion for 90 minutes on day 1 of each 21 day as a treatment cycle. Number of Cycles: until progression or unacceptable toxicity develops. Other Names: liposome irinotecan
Active Comparator: 2. irinotecan	Drug: irinotecan 300 mg/m2, IV infusion on day 1 of each 21 day as a treatment cycle. Number of Cycles: until progression or unacceptable toxicity develops. Other Names: Campto
Active Comparator: 3. docetaxel	Drug: docetaxel 75 mg/m2, IV infusion for 60 minutes on day 1 of each 21 day as a treatment cycle. Number of Cycles: until progression or unacceptable toxicity develops. Other Names: Taxetere

Arm

Intervention/Treatment

Experimental: 1. PEP02

liposome irinotecan

Drug: PEP02

120 mg/m2, IV infusion for 90 minutes on day 1 of each 21 day as a treatment cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Other Names:

liposome irinotecan

Active Comparator: 2. irinotecan

Drug: irinotecan

300 mg/m2, IV infusion on day 1 of each 21 day as a treatment cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Other Names:

Campto

Active Comparator: 3. docetaxel

Drug: docetaxel

75 mg/m2, IV infusion for 60 minutes on day 1 of each 21 day as a treatment cycle. Number of Cycles: until progression or unacceptable toxicity develops.

Other Names:

Taxetere

Outcome Measures

Primary Outcome Measures

objective tumor response []

Secondary Outcome Measures

progression-free survival, duration of tumor response, time to progression, time to treatment failure, disease control rate, 1-year survival rate,and overall survival; pharmacokinetics and pharmacogenetics of PEP02 and irinotecan []

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 locally advanced (unresectable) or metastatic adenocarcinoma of gastric or gastroesophageal junction
Failed to only one systemic chemotherapy for locally advanced or metastatic disease, including patients whose diseases recur within 6 months after (neo)adjuvant chemotherapy. Chemotherapy administered with concurrent radiotherapy is NOT considered as systemic chemotherapy.
Have at least one measurable lesion according to the RECIST criteria
Aged above or equal to 18 years, at the time of acquisition of informed consent
With ECOG performance status 0, 1, or 2
Life expectancy equal to or more than 3 months
With adequate organ and marrow function as defined below:
With ability to understand and the willingness to sign a written Informed Consent Form

Exclusion Criteria:

Had systemic chemotherapy within 3 weeks before the commencement of study treatment
Had radiotherapy within 4 weeks before the commencement of study treatment
With known brain metastasis
With active multiple cancers or had treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer
With prior irinotecan or taxane (paclitaxel, docetaxel) treatment
Have received irradiation affecting > 30% of the active bone marrow
Had major surgery within 4 weeks of the start of study treatment (laparotomy, line placement is not considered major surgery)
Have not recovered from prior treatments
With preexisting peripheral neuropathy > grade 2
With history of allergic reaction to liposome product or other drugs formulated with polysorbate
With uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, active gastrointestinal bleeding, watery stools, central nervous system disorders or psychiatric illness/social situation that would limit compliance with study requirements or judged to be ineligible for the study by the investigator
Have received any investigational agents within 3 weeks preceding the start of study treatment
Pregnant or breastfeeding females (a pregnancy test must be performed on all female patients who are of child-bearing potential before entering the study, and the result must be negative)
With intestinal obstruction
Have received St. John's Wort, CYP3A4 inducing anticonvulsants (phenytoin, phenobarbital, and carbamazepine), rifampin and rifabutin within two weeks, or ketoconazole, itraconazole, troleandomycin, erythromycin, diltiazem and verapamil within one week before the administration of study medications

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Clinical Hospital Mostar	Mostar	Bosnia and Herzegovina	36 000
2	Clinical Centre University of Sarajevo	Sarajevo	Bosnia and Herzegovina	71 000
3	University Hospital Centre Rijeka	Rijeka	Croatia	51 000
4	University Hospital Centre Dubrava	Zagreb	Croatia	10 000
5	University Hospital Centre Zagreb	Zagreb	Croatia	10 000
6	Samsung Medical Center	Seoul	Korea, Republic of	135-710
7	Asan Medical Center	Seoul	Korea, Republic of	138-736
8	National Cancer Center	Seoul	Korea, Republic of	410-769
9	Hospital Universitario Vall d'Hebron	Barcelona	Spain	08035
10	Hospital General Universitario de Elche	Elche	Spain	03203
11	Hospital Clínico San Carlos	Madrid	Spain	28040
12	Hospital Universitario Marques de Valdecilla	Santander	Spain	39008
13	Chang Gung Memorial Hospital - Chiayi	Chiayi	Taiwan
14	Chang Gung Memorial Hospital - LinKou	LinKou	Taiwan
15	National Cheng Kung University Hospital	Tainan	Taiwan	704
16	Taipei Veterans General Hospital	Taipei	Taiwan	112
17	Mackay Memorial Hospital	Taipei	Taiwan	25115
18	Addenbrookes Hospital Oncology Center	Cambridge	United Kingdom	CB2 2QQ
19	Guy's & St Thomas' NHS Foundation Trust	London	United Kingdom	SE19RT
20	Kent Oncology Centre, Maidstone Hospital	Maidstone	United Kingdom	ME16 9QQ
21	Southampton University Hospital	Southampton	United Kingdom	SO16 6YD
22	The Royal Marsden Hospital	Surrey	United Kingdom	SM2 5PT