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

Stomach Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00813072
• Other study ID #: PEP0206
• Secondary ID: EudraCT number:
• Status: Completed
• Phase: Phase 2
• First received: December 18, 2008
• Last updated: March 1, 2012
• Start date: November 2007
• Est. completion date: December 2010

Study information

• Verified date: March 2012
• Source: PharmaEngine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencySpain: Ministry of Health and ConsumptionTaiwan: Department of HealthCroatia: Ministry of Health and Social CareKorea: Food and Drug AdministrationBosnia: Federal Ministry of Health
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: December 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Neoplasms
• Neoplasms
• Stomach Neoplasms

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
Bosnia and Herzegovina	Clinical Hospital Mostar	Mostar
Bosnia and Herzegovina	Clinical Centre University of Sarajevo	Sarajevo
Croatia	University Hospital Centre Rijeka	Rijeka
Croatia	University Hospital Centre Dubrava	Zagreb
Croatia	University Hospital Centre Zagreb	Zagreb
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	National Cancer Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital General Universitario de Elche	Elche
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander
Taiwan	Chang Gung Memorial Hospital - Chiayi	Chiayi
Taiwan	Chang Gung Memorial Hospital - LinKou	LinKou
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United Kingdom	Addenbrookes Hospital Oncology Center	Cambridge
United Kingdom	Guy's & St Thomas' NHS Foundation Trust	London
United Kingdom	Kent Oncology Centre, Maidstone Hospital	Maidstone
United Kingdom	Southampton University Hospital	Southampton
United Kingdom	The Royal Marsden Hospital	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
PharmaEngine

Countries where clinical trial is conducted

Bosnia and Herzegovina,  Croatia,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	objective tumor response			No
Secondary	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			No