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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Ganymed Pharmaceuticals AG
ClinicalTrials.gov Identifier:
NCT01671774
First received: August 21, 2012
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
CLDN18.2-positive Gastric Adenocarcinoma
CLDN18.2-positive Adenocarcinoma of Esophagus
CLDN18.2-positive Adenocarcinoma of the Gastroesophageal Junction
Drug: IMAB362
Drug: Zoledronic acid
Drug: Interleukin-2 (1 million IU)
Drug: Interleukin-2 (3 million IU)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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 Gastro-esophageal Junction.

Resource links provided by NLM:


Further study details as provided by Ganymed Pharmaceuticals AG:

Primary Outcome Measures:
  • Safety and Tolerability [ Time Frame: at least 18 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.

  • Immune cell profile and kinetics [ Time Frame: at least 18 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: at least 18 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: at least 18 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.

  • Disease control rate (DCR) [ Time Frame: at least 18 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 18 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: 20
Study Start Date: August 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IMAB362 + ZA Drug: IMAB362
800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle
Drug: Zoledronic acid
4 mg on d 1 of cycle 1 and cycle 3
Experimental: IMAB362 + ZA + IL-2 (1 million IU) Drug: IMAB362
800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle
Drug: Zoledronic acid
4 mg on d 1 of cycle 1 and cycle 3
Drug: Interleukin-2 (1 million IU)
1 million IU on day 1, 2 and 3 of cycles 1 and 3.
Experimental: IMAB362 + ZA + IL-2 (3 million IU) Drug: IMAB362
800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle
Drug: Zoledronic acid
4 mg on d 1 of cycle 1 and cycle 3
Drug: Interleukin-2 (3 million IU)
3 million IU on day 1, 2 and 3 of cycles 1 and 3.
Active Comparator: IMAB362 Drug: IMAB362
800 mg/m2 on d 1 of cycle 1. 600 mg/m2 on d 1 of every other cycle

  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, 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)
  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: NCT01671774

Locations
Germany
Institut für Klinische Forschung, Krankenhaus Nordwest GmbH
Frankfurt, Hessen, Germany, 60488
BAG / Onkologische Schwerpunktpraxis
Dresden, Sachsen, Germany, 01307
Charité Universitätsmedizin Berlin - CVK, Med. Klinik m.S. Hämatologie und Onkologie
Berlin, Germany, 13353
Freiburg University Medical Center, Department of Internal Medicine II, Gastroenterology and Hepatology
Freiburg, Germany, 79106
Leipzig University Hospital, University Cancer Center (UCCL)
Leipzig, Germany, 04109
University Hospital Tuebingen, Department of Internal Medicine I - Gastroenterology, Hepatology, Infectious Diseases
Tübingen, Germany, 72076
Ulm University Hospital, Center for Internal Medicine
Ulm, Germany, 89070
Latvia
Piejuras Hospital, Oncology Clinic
Liepaja, Latvia, 3401
Riga East University Hospital, LLC, Latvian Oncology Center
Riga, Latvia, LV1038
Sponsors and Collaborators
Ganymed Pharmaceuticals AG
  More Information

No publications provided

Responsible Party: Ganymed Pharmaceuticals AG
ClinicalTrials.gov Identifier: NCT01671774     History of Changes
Other Study ID Numbers: GM-IMAB-001-04, 2011-005509-64
Study First Received: August 21, 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
Zoledronic acid
Diphosphonates
Interleukin-2
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 16, 2014