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

CLDN18.2-positive Adenocarcinoma of Esophagus Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01671774
• Other study ID #: GM-IMAB-001-04
• Secondary ID: 2011-005509-64
• Status: Completed
• Phase: Phase 1
• Start date: October 16, 2012
• Est. completion date: October 13, 2014

Study information

• Verified date: October 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 13, 2014
• Est. primary completion date: October 13, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Drug:
• IMAB362
800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle
• Zoledronic acid
4 mg on d 1 of cycle 1 and cycle 3
• Interleukin-2 (1 million IU)
1 million IU on day 1, 2 and 3 of cycles 1 and 3.
• Interleukin-2 (3 million IU)
3 million IU on day 1, 2 and 3 of cycles 1 and 3.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.

Countries where clinical trial is conducted

Germany,  Latvia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	at least 18 months
Primary	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.	at least 18 months
Secondary	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.	at least 18 months
Secondary	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.	at least 18 months
Secondary	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.	at least 18 months
Secondary	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.	at least 18 months