Efficacy and Safety of IMAB362 in Combination With the EOX Regimen for CLDN18.2-positive Gastric Cancer (FAST)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Ganymed Pharmaceuticals AG
Sponsor:
Information provided by (Responsible Party):
Ganymed Pharmaceuticals AG
ClinicalTrials.gov Identifier:
NCT01630083
First received: June 19, 2012
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
CLDN18.2-positive Gastric Adenocarcinoma
CLDN18.2-positive Adenocarcinoma of Esophagus
CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction
Drug: Epirubicin
Drug: Oxaliplatin
Drug: Capecitabine
Drug: IMAB362 800/600 mg/m2
Drug: IMAB362 1000 mg/m2
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Multicenter, Open-Label Study Evaluating the Efficacy and Safety of IMAB362 in Combination With the EOX Regimen as First-Line Treatment of Patients With CLDN18.2-positive Adenocarcinomas of the Stomach, the Esophagus or the Gastroesophageal Junction.

Resource links provided by NLM:


Further study details as provided by Ganymed Pharmaceuticals AG:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: at least 33 months ] [ Designated as safety issue: No ]
    PFS is defined as the time from randomization of therapy to the first observation of disease progression or death from any cause or last tumor evaluation if free of progression. For patients who have not progressed either clinically or on the last scan, they will be censured as of the last tumor evaluation.

  • Safety and Tolerability [ Time Frame: at least 33 months ] [ Designated as safety issue: Yes ]
    Descriptive statistics for treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.


Secondary Outcome Measures:
  • Survival rate at 12 months [ Time Frame: at least 33 months ] [ Designated as safety issue: No ]
    To determine survival status at 12 months following initiation of therapy each patient will be classified as alive or dead (irrespective of cause of death). For this purpose, upon completion of the last cycle, all patients will continue to be followed until death or loss to follow up. Patients who discontinue treatment due to progression will be followed in the same manner.

  • Overall survival (OS) [ Time Frame: at least 33 months ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization to death from any cause or last contact if alive.

  • Time to progression (TTP) [ Time Frame: at least 33 months ] [ Designated as safety issue: No ]
    TTP is defined as the time from randomization of therapy to the first observation of confirmed disease progression. For patients who have not progressed either clinically or on the last scan, they will be censured as of the last tumor evaluation.

  • Objective tumor response rate (ORR) [ Time Frame: at least 33 months ] [ Designated as safety issue: No ]
    ORR comprises the fraction of patients with CR, PR according to RECIST v1.1. It is set in relation to the ITT population and PP population (see section 8).

  • Disease control rate (DCR) [ Time Frame: at least 33 months ] [ Designated as safety issue: No ]
    DCR is defined as the fraction of patients with CR or PR or SD according to RECIST v1.1. It is set in relation to the ITT population and PP population

  • Duration of response (DOR) [ Time Frame: at least 33 months ] [ Designated as safety issue: No ]
    Duration of response is determined as the time when criteria for CR, PR, and SD are first met until the first date that recurrent or progressive disease or death occurs.


Estimated Enrollment: 210
Study Start Date: June 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: EOX Drug: Epirubicin
50 mg/m2; d 1 q3w for max. 8 cycles
Drug: Oxaliplatin
130 mg/m2; d 1 q3w for max. 8 cycles
Drug: Capecitabine
625 mg/m2; p.o. d 1 - d 21 q3w twice daily for max. 8 cycles
Experimental: EOX + IMAB362 800/600 mg/m2 Drug: Epirubicin
50 mg/m2; d 1 q3w for max. 8 cycles
Drug: Oxaliplatin
130 mg/m2; d 1 q3w for max. 8 cycles
Drug: Capecitabine
625 mg/m2; p.o. d 1 - d 21 q3w twice daily for max. 8 cycles
Drug: IMAB362 800/600 mg/m2
800 mg/m2 loading dose on cycle 1. 600 mg/m2 every 3 weeks.
Experimental: EOX + IMAB362 1000 mg/m2 Drug: Epirubicin
50 mg/m2; d 1 q3w for max. 8 cycles
Drug: Oxaliplatin
130 mg/m2; d 1 q3w for max. 8 cycles
Drug: Capecitabine
625 mg/m2; p.o. d 1 - d 21 q3w twice daily for max. 8 cycles
Drug: IMAB362 1000 mg/m2
1000 mg/m2 every 3 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01630083

Contacts
Contact: Angelika Schönfeld QA-GCP@ganymed.ag

  Show 55 Study Locations
Sponsors and Collaborators
Ganymed Pharmaceuticals AG
Investigators
Principal Investigator: Martin Schuler, Prof. Dr. Universitätsklinikum Essen; Innere Klinik Tumorforschung; Hufelandstrasse 55, 45122 Essen
  More Information

No publications provided

Responsible Party: Ganymed Pharmaceuticals AG
ClinicalTrials.gov Identifier: NCT01630083     History of Changes
Other Study ID Numbers: GM-IMAB-001-03, 2011-005285-38
Study First Received: June 19, 2012
Last Updated: May 6, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 15, 2014