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Safety and Activity of IMAB362 in Combination With Zoledronic Acid and Interleukin-2 in CLDN18.2-positive Gastric Cancer (PILOT)

Primary Purpose

CLDN18.2-positive Gastric Adenocarcinoma, CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction, CLDN18.2-positive Adenocarcinoma of Esophagus

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
IMAB362
Zoledronic acid
Interleukin-2 (1 million IU)
Interleukin-2 (3 million IU)
Sponsored by
Astellas Pharma Global Development, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for CLDN18.2-positive Gastric Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction
  • Inoperable locally advanced disease, resections with R0, R1 or R2 outcome 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 RECIST v1.1
  • Age ≥ 18 years
  • Written informed consent
  • ECOG performance status (PS) 0-1
  • Life expectancy > 3 months

Exclusion Criteria:

  • Prior hypersensitivity reaction or intolerance to one of the compounds of the study treatment
  • Known HIV infection or known symptomatic hepatitis (A, B, C)
  • Clinical symptoms of cerebral metastases
  • Pregnancy or breastfeeding
  • Patients treated with any bisphosphonate-based therapeutic for any indication during the previous year
  • Hypocalcemia that requires medication. Corrected (adjusted for serum albumin) serum calcium < 8 mg/dl (2 mmol/L) or > 12 mg/dL (3.0 mmol/L)

Sites / Locations

  • Institut für Klinische Forschung, Krankenhaus Nordwest GmbH
  • BAG / Onkologische Schwerpunktpraxis
  • Charité Universitätsmedizin Berlin - CVK, Med. Klinik m.S. Hämatologie und Onkologie
  • Freiburg University Medical Center, Department of Internal Medicine II, Gastroenterology and Hepatology
  • Leipzig University Hospital, University Cancer Center (UCCL)
  • University Hospital Tuebingen, Department of Internal Medicine I - Gastroenterology, Hepatology, Infectious Diseases
  • Ulm University Hospital, Center for Internal Medicine
  • Piejuras Hospital, Oncology Clinic
  • Riga East University Hospital, LLC, Latvian Oncology Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

IMAB362 + ZA

IMAB362 + ZA + IL-2 (1 million IU)

IMAB362 + ZA + IL-2 (3 million IU)

IMAB362

Arm Description

Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1.

Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.

Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.

Participants received IMAB362 only on Day 1 of each cycle every 3 weeks.

Outcomes

Primary Outcome Measures

Safety and Tolerability
Descriptive statistics for treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.
Immune cell profile and kinetics
Descriptive statistics for treatments will be given on the number and activity of immune cells in peripheral blood of patients.

Secondary Outcome Measures

Progression-free survival (PFS)
PFS is defined as the time from registration 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.
Objective tumor response rate (ORR)
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.
Disease control rate (DCR)
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)
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.

Full Information

First Posted
August 21, 2012
Last Updated
October 16, 2019
Sponsor
Astellas Pharma Global Development, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01671774
Brief Title
Safety and Activity of IMAB362 in Combination With Zoledronic Acid and Interleukin-2 in CLDN18.2-positive Gastric Cancer
Acronym
PILOT
Official Title
Multicenter, Open-label, Exploratory Phase I Pilot Study to Investigate Safety, Pharmacodynamics, and Pharmacokinetics of Immunological Effects and Activity of Combining Multiple Doses of IMAB362 With Immunomodulation (Zoledronic Acid, Interleukin-2) in Patients With Advanced Adenocarcinoma of the Stomach, the Lower Esophagus, or the Gastroesophageal Junction
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
October 16, 2012 (Actual)
Primary Completion Date
October 13, 2014 (Actual)
Study Completion Date
October 13, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Global Development, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of the trial is to assess the immunological effects and their kinetics, the safety and activity of IMAB362 plus Zoledronic acid with/without low to intermediate doses of Interleukin-2 in subjects with advanced gastroesophageal cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CLDN18.2-positive Gastric Adenocarcinoma, CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction, CLDN18.2-positive Adenocarcinoma of Esophagus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Allocation
Non-Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IMAB362 + ZA
Arm Type
Experimental
Arm Description
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1.
Arm Title
IMAB362 + ZA + IL-2 (1 million IU)
Arm Type
Experimental
Arm Description
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.
Arm Title
IMAB362 + ZA + IL-2 (3 million IU)
Arm Type
Experimental
Arm Description
Participants received IMAB362 on Day 1 of each 3-week cycle (every 3 weeks). Participants received ZA on Day 1 and IL-2 on Days 1 to 3 of Cycles 1 and 3 only.
Arm Title
IMAB362
Arm Type
Active Comparator
Arm Description
Participants received IMAB362 only on Day 1 of each cycle every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
IMAB362
Intervention Description
800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle
Intervention Type
Drug
Intervention Name(s)
Zoledronic acid
Intervention Description
4 mg on d 1 of cycle 1 and cycle 3
Intervention Type
Drug
Intervention Name(s)
Interleukin-2 (1 million IU)
Intervention Description
1 million IU on day 1, 2 and 3 of cycles 1 and 3.
Intervention Type
Drug
Intervention Name(s)
Interleukin-2 (3 million IU)
Intervention Description
3 million IU on day 1, 2 and 3 of cycles 1 and 3.
Primary Outcome Measure Information:
Title
Safety and Tolerability
Description
Descriptive statistics for treatments will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.
Time Frame
at least 18 months
Title
Immune cell profile and kinetics
Description
Descriptive statistics for treatments will be given on the number and activity of immune cells in peripheral blood of patients.
Time Frame
at least 18 months
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
PFS is defined as the time from registration 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.
Time Frame
at least 18 months
Title
Objective tumor response rate (ORR)
Description
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.
Time Frame
at least 18 months
Title
Disease control rate (DCR)
Description
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.
Time Frame
at least 18 months
Title
Duration of response (DOR)
Description
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.
Time Frame
at least 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed adenocarcinoma of the stomach, the esophagus or the gastroesophageal junction Inoperable locally advanced disease, resections with R0, R1 or R2 outcome 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 RECIST v1.1 Age ≥ 18 years Written informed consent ECOG performance status (PS) 0-1 Life expectancy > 3 months Exclusion Criteria: Prior hypersensitivity reaction or intolerance to one of the compounds of the study treatment Known HIV infection or known symptomatic hepatitis (A, B, C) Clinical symptoms of cerebral metastases Pregnancy or breastfeeding Patients treated with any bisphosphonate-based therapeutic for any indication during the previous year Hypocalcemia that requires medication. Corrected (adjusted for serum albumin) serum calcium < 8 mg/dl (2 mmol/L) or > 12 mg/dL (3.0 mmol/L)
Facility Information:
Facility Name
Institut für Klinische Forschung, Krankenhaus Nordwest GmbH
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
60488
Country
Germany
Facility Name
BAG / Onkologische Schwerpunktpraxis
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
Facility Name
Charité Universitätsmedizin Berlin - CVK, Med. Klinik m.S. Hämatologie und Onkologie
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Freiburg University Medical Center, Department of Internal Medicine II, Gastroenterology and Hepatology
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Leipzig University Hospital, University Cancer Center (UCCL)
City
Leipzig
ZIP/Postal Code
04109
Country
Germany
Facility Name
University Hospital Tuebingen, Department of Internal Medicine I - Gastroenterology, Hepatology, Infectious Diseases
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Ulm University Hospital, Center for Internal Medicine
City
Ulm
ZIP/Postal Code
89070
Country
Germany
Facility Name
Piejuras Hospital, Oncology Clinic
City
Liepaja
ZIP/Postal Code
3401
Country
Latvia
Facility Name
Riga East University Hospital, LLC, Latvian Oncology Center
City
Riga
ZIP/Postal Code
LV1038
Country
Latvia

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Learn more about this trial

Safety and Activity of IMAB362 in Combination With Zoledronic Acid and Interleukin-2 in CLDN18.2-positive Gastric Cancer

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