Clinical trial NCT01630083: Efficacy and Safety of IMAB362 in Combination With the EOX Regimen for CLDN18.2-positive Gastric Cancer
Official title: A Randomized Phase II Multicenter, Open-Label Study Evaluating the Efficacy and Safety of IMAB362 in Combination With the EOX (Epirubicin, Oxaliplatin, Capecitabine) Regimen as First-Line Treatment of Patients With CLDN18.2-Positive Advanced Adenocarcinomas of the Stomach, the Esophagus or the Gastroesophageal Junction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction
CLDN18.2-positive Adenocarcinoma of Esophagus
CLDN18.2-positive Gastric Adenocarcinoma
Keywords: IMAB362
ASP8951
zolbetuximab
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-06-28
Enrollment: 252
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 the trial is to assess the therapeutic effects and the safety profile of IMAB362 combined with EOX (epirubicin, oxaliplatin, capecitabine) as first-line treatment for patients with advanced adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction compared to EOX alone.

Furthermore, sufficient binding of IMAB362 to the target cells is necessary for antitumoral activity. Thus, two dose levels ensuring a serum level above the in vitro predicted clinical efficacy threshold will be investigated.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction
* Inoperable locally advanced disease or resections with R2 outcome or recurrent or metastatic disease.
* CLDN18.2 expression confirmed by immunohistochemistry in paraffin embedded tumor tissue sample.
* Measurable and/or non-measurable disease as defined according to RECISTv1.1
* Age ≥ 18 years
* Written Informed Consent Form
* ECOG performance status (PS) 0-1
* Life expectancy \> 3 months
* HER2/neu negative patients and patients with HER2/neu positive status but not eligible to trastuzumab therapy in discretion of the investigator.
* Adequate cardiac, hepatic, renal, hematologic function.

Exclusion Criteria:

* Prior severe allergic reaction or intolerance to a monoclonal antibody, to the chemotherapeutics used in this study or any excipient in the respective formulations.
* Previous chemotherapy for advanced disease.
* Previous perioperative chemotherapy with curative intention within 6 months of start of study treatment. If interval is longer than 6 months (counted from the stop date of the perioperative chemotherapy), patients are allowed.
* Known HIV infection or known symptomatic hepatitis (A, B, C).
* Symptomatic cerebral metastases.
* Pregnancy or breastfeeding.
* Previous treatments with maximum cumulative doses of epirubicin \> 500 mg/m² and/or other anthracyclines and anthracenediones.
* Known dihydropyrimidine dehydrogenase (DPD) deficiency.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From randomization to the data cut-off date of 31JAN2019; maximum time on follow-up was, 68.2, 47.2 & 59.6 months in the EOX, EOX+Zolbetuximab 600 mg, and EOX+Zolbetuximab 1000 mg treatment groups respectively.
measure: Number of Participants with Adverse Events (AEs)
timeFrame: From the first dose of study drug administration up to 30 days after the last study medication administration (up to 1791 days).
Secondary outcomes:
measure: Clinical PFS
timeFrame: From randomization to the data cut-off date of 31JAN2019; maximum time on follow-up was, 68.2, 47.2 & 59.6 months in the EOX, EOX+Zolbetuximab 600 mg, and EOX+Zolbetuximab 1000 mg treatment groups respectively.
measure: Overall Survival Rate at 12 Months
timeFrame: Up to 12 months
measure: Overall Survival (OS)
timeFrame: From randomization to the data cut-off date of 31JAN2019; maximum time on follow-up was, 68.2, 47.2 & 59.6 months in the EOX, EOX+Zolbetuximab 600 mg, and EOX+Zolbetuximab 1000 mg treatment groups respectively.
measure: Time to Progression (TTP)
timeFrame: From randomization to the data cut-off date of 31JAN2019; maximum time on follow-up was, 68.2, 47.2 & 59.6 months in the EOX, EOX+Zolbetuximab 600 mg, and EOX+Zolbetuximab 1000 mg treatment groups respectively.
measure: Objective Tumor Response Rate (ORR)
timeFrame: Up to week 94
measure: Disease Control Rate (DCR)
timeFrame: Up to week 94
measure: Duration of Response (DOR)
timeFrame: From randomization to the data cut-off date of 31JAN2019; maximum time on follow-up was, 68.2, 47.2 & 59.6 months in the EOX, EOX+Zolbetuximab 600 mg, and EOX+Zolbetuximab 1000 mg treatment groups respectively.
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: Site BUL004
city: Sofia
country: Bulgaria
facility: Site BUL001
city: Sofia
country: Bulgaria
facility: Site BUL003
city: Sofia
country: Bulgaria
facility: Site BUL005
city: Varna
country: Bulgaria
facility: Site BUL002
city: Olomouc
country: Czechia
facility: Site CZE002
city: Znojmo
country: Czechia
facility: Site CZE001
city: Bielefeld
country: Germany
facility: Site GER012
city: Bochum
country: Germany
facility: Site GER029-01
city: Bochum
country: Germany
facility: Site GER029
city: Dresden
country: Germany
facility: Site GER010
city: Essen
country: Germany
facility: Site GER001
city: Frankfurt
country: Germany
facility: Site GER017
city: Halle/Saale
country: Germany
facility: Site GER005
city: Leipzig
country: Germany
facility: Site GER020
city: Münster
country: Germany
facility: Site GER016
city: Pinneberg
country: Germany
facility: Site GER013
city: Liepaja
country: Latvia
facility: Site LAT001
city: Riga
country: Latvia
facility: Site LAT002
city: Arkhangelsk
country: Russian Federation
facility: Site RUS011
city: Bryansk
country: Russian Federation
facility: Site RUS016
city: Chelyabinsk
country: Russian Federation
facility: Site RUS006
city: Ivanovo
country: Russian Federation
facility: Site RUS007
city: Kursk
country: Russian Federation
facility: Site RUS009
city: Moscow
country: Russian Federation
facility: Site RUS001
city: Novgorod
country: Russian Federation
facility: Site RUS017
city: Obninsk
country: Russian Federation
facility: Site RUS002
city: Omsk
country: Russian Federation
facility: Site RUS023
city: Orel
country: Russian Federation
facility: Site RUS012
city: Orenburg
country: Russian Federation
facility: Site RUS014
city: Pyatigorsk
country: Russian Federation
facility: Site RUS005
city: Ryazan
country: Russian Federation
facility: Site RUS019
city: St.Petersburg
country: Russian Federation
facility: Site RUS003
city: St.Petersburg
country: Russian Federation
facility: Site RUS010
city: St.Petersburg
country: Russian Federation
facility: Site RUS015
city: Yaroslavl
country: Russian Federation
facility: Site RUS013
city: Dnipropetrovsk
country: Ukraine
facility: Site UKR003
city: Donetsk
country: Ukraine
facility: Site UKR001
city: Donetsk
country: Ukraine
facility: Site UKR002
city: Ivano-Frankivsk
country: Ukraine
facility: Site UKR008
city: Kharkiv
country: Ukraine
facility: Site UKR005
city: Kyiv
country: Ukraine
facility: Site UKR007
city: Lviv
country: Ukraine
facility: Site UKR006
city: Poltava
country: Ukraine
facility: Site UKR015
city: Simferopol
country: Ukraine
facility: Site UKR004
city: Sumy
country: Ukraine
facility: Site UKR011
city: Uzhhorod
country: Ukraine
facility: Site UKR010
city: Zaporizhia
country: Ukraine
facility: Site UKR009
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Executive Director
role: STUDY_DIRECTOR
References: