Clinical trial NCT00813072: Study of PEP02, Irinotecan or Docetaxel in Gastric or Gastroesophageal Junction Adenocarcinoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stomach Neoplasms
Esophageal Neoplasms
Keywords: Gastric Cancer
Stomach Cancer
Gastroesophageal
Gastroesophageal Junction
Esophageal Cancer
phase II
PEP02
randomization
randomisation
adenocarcinoma
locally advanced
metastatic
simon's two
Lead sponsor: PharmaEngine
Sponsor class: INDUSTRY
First posted: 2008-12-22
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: objective tumor response
Secondary outcomes:
measure: 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
Other outcomes:
Locations:
city: Mostar
country: Bosnia and Herzegovina
facility: Clinical Hospital Mostar
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical Centre University of Sarajevo
city: Rijeka
country: Croatia
facility: University Hospital Centre Rijeka
city: Zagreb
country: Croatia
facility: University Hospital Centre Dubrava
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: National Cancer Center
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Chiayi
country: Taiwan
facility: Chang Gung Memorial Hospital - Chiayi
city: LinKou
country: Taiwan
facility: Chang Gung Memorial Hospital - LinKou
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital Oncology Center
city: London
country: United Kingdom
facility: Guy's & St Thomas' NHS Foundation Trust
city: Maidstone
country: United Kingdom
facility: Kent Oncology Centre, Maidstone Hospital
city: Southampton
country: United Kingdom
facility: Southampton University Hospital
city: Surrey
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: The Royal Marsden Hospital, London & Surrey, UK
name: David Cunningham
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. doi: 10.1093/annonc/mdt002. Epub 2013 Feb 13.