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A Study of IMU-131 Plus Standard of Care Chemotherapy in Patients With HER2/Neu Overexpressing Advanced Cancer of the Stomach

This study is currently recruiting participants.
Verified July 2017 by Imugene Limited
Sponsor:
ClinicalTrials.gov Identifier:
NCT02795988
First Posted: June 10, 2016
Last Update Posted: September 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Imugene Limited
  Purpose
The Phase 1b study is an open-label, multicenter dose escalation study designed to assess the safety, tolerability, immunogenicity and recommended phase 2 dose (RP2D) of IMU-131. The RP2D will be evaluated in the dose expansion Phase 2 study.

Condition Intervention Phase
Gastrointestinal Neoplasms Adenocarcinoma Biological: IMU-131 Drug: Cisplatin and either Fluorouracil (5-FU) or Capecitabine Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:
Open label study
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Open-label Study of IMU-131 HER2/Neu Peptide Vaccine Plus Cisplatin and Either 5-Fluorouracil or Capecitabine Chemotherapy in Patients With HER2/Neu Overexpressing Metastatic or Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction

Resource links provided by NLM:


Further study details as provided by Imugene Limited:

Primary Outcome Measures:
  • Incidence of treatment-emergent adverse events [ Time Frame: Day 0 to Day 56 ]
    To be evaluated by the number, duration and severity of treatment emergent adverse events (AEs).

  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Day 0 to Day 56 ]
    To be evaluated by safety/tolerability and immunogenicity data for IMU-131 (P467-specific antibodies (IgG) and Her-2- specific antibodies (IgG) titers).


Other Outcome Measures:
  • Exploratory Outcome: Humoral immunogenicity evaluated by P467-specific antibodies (IgG) and Her-2- specific antibodies (IgG) [ Time Frame: Day 0 to Day 56 ]
    Antibodies analysed in serum samples taken across study visits

  • Exploratory Outcome: Cellular immunogenicity evaluated by vaccine-specific cytokine levels as well as analysis of regulatory and effector T and B cells [ Time Frame: Day 0 to Day 56 ]
    Vaccine-specific cytokine levels and regulatory and effector T and B cells analysed in whole blood samples taken at Day 0 and Day 56

  • Exploratory Outcome: Radiographic data measured by RECIST 1.1 criteria [ Time Frame: Day 0 to Day 56 and during Long-term maintenance ]
    Radiographic data will be analyzed descriptively to explore the Response Rate (RR)


Estimated Enrollment: 18
Actual Study Start Date: August 30, 2017
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low Dose
10 μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine
Biological: IMU-131
IMU-131 vaccine is a P467-CRM197 peptide antigen in PBS buffer and Montanide ISA 51 Sterile adjuvant
Other Name: HER-Vaxx
Drug: Cisplatin and either Fluorouracil (5-FU) or Capecitabine
Chemotherapy to include the following: cisplatin, IV (80 mg/m2 on Day 14, then every 21 days) and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous infusion for 96 hours on days 14 to 17, then every 21 days) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 14 to 27, then every 21 days).
Other Name: Standard of Care Chemotherapy
Experimental: Mid Dose
30 μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine
Biological: IMU-131
IMU-131 vaccine is a P467-CRM197 peptide antigen in PBS buffer and Montanide ISA 51 Sterile adjuvant
Other Name: HER-Vaxx
Drug: Cisplatin and either Fluorouracil (5-FU) or Capecitabine
Chemotherapy to include the following: cisplatin, IV (80 mg/m2 on Day 14, then every 21 days) and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous infusion for 96 hours on days 14 to 17, then every 21 days) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 14 to 27, then every 21 days).
Other Name: Standard of Care Chemotherapy
Experimental: High Dose
50 μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine
Biological: IMU-131
IMU-131 vaccine is a P467-CRM197 peptide antigen in PBS buffer and Montanide ISA 51 Sterile adjuvant
Other Name: HER-Vaxx
Drug: Cisplatin and either Fluorouracil (5-FU) or Capecitabine
Chemotherapy to include the following: cisplatin, IV (80 mg/m2 on Day 14, then every 21 days) and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous infusion for 96 hours on days 14 to 17, then every 21 days) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 14 to 27, then every 21 days).
Other Name: Standard of Care Chemotherapy

Detailed Description:

IMU-131 is a single peptide structure composed of 3 individual B-cell epitope peptide sequences selected from HER2/neu structure. Polyclonal antibodies against IMU-131 peptides bind three separate regions of the HER2 receptor and also to the dimerization loop of the HER2 receptor, preventing dimerization, which in turn inhibits intracellular signaling. This blockade of the HER2 signaling pathways is thought to be substantially greater than that with trastuzumab alone. Safety and immunogenicity of the 3 peptides have been shown in Phase 1a testing of an earlier formulation of IMU-131. The shelf stability of the Phase 1a vaccine was not optimal and hence the formulation was adjusted for IMU-131. The three B-cell epitope peptides (P4, P6 and P7) were combined in a specific order resulting in a single fusion peptide of 49 amino acids in length (P467). This new formulation of IMU-131 has extended stability and improved immunogenicity compared to the formulation used previously. The new vaccine IMU-131 produces a stronger and more rapid polyclonal antibody response and is efficient to manufacture compared with previous formulations. Based on these three known epitopes (P4, P6 and P7), the investigators developed a single peptide antigen (P467), which allows simplification of the manufacturing process.

It is hypothesized that administration of IMU-131 in addition to chemotherapy will prolong survival and may delay tumor progression and/or reduce tumor burden in patients with HER2/neu overexpressing gastric or gastroesophageal junction (GEJ) adenocarcinoma (otherwise known as Advanced Cancer of the Stomach (ASC)).

The Phase 1b study aims to determine the safety and tolerability of IMU 131 and identify the Recommended Phase 2 Dose (RP2D) of IMU 131 in combination with chemotherapy in HER2/neu overexpressing ACS to carry into the Phase 2 dose expansion study. The Phase 2 component will be submitted as an amendment and will be initiated following completion of Phase 1b. Phase 2 will be designed to further characterize the safety and to explore clinical activity of IMU-131 in combination with chemotherapy in HER2/neu overexpressing ACS.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient has been informed of the investigational nature of this study and has given written informed consent in accordance with institutional, local, and national guidelines;
  2. Age ≥ 20 years old;
  3. Life expectancy of at least 12 weeks;
  4. No prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer within 6 months prior to Day 0;
  5. Metastatic gastric or GEJ adenocarcinoma, or locally advanced disease not amenable to surgical resection;
  6. HER2/neu overexpression (3+ by immunohistochemistry (IHC) or if IHC 2+ confirmed by fluorescent in situ hybridization [FISH] or chromogenic in situ hybridization [CISH]);
  7. ECOG performance status 0-1;
  8. At least one measurable lesion as defined by RECIST 1.1 criteria;
  9. Adequate left ventricular ejection function at baseline, defined as LVEF > 50% by echocardiogram or MUGA scan (Multi Gated Acquisition Scan);
  10. Adequate hematologic function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL;
  11. Adequate liver function evidenced by bilirubin ≤ 1.5 x laboratory upper limit of normal [ULN], and ALT and AST ≤ 3 x laboratory ULN if no liver involvement or ALT and AST ≤ 5 times laboratory ULN with liver involvement;
  12. Adequate renal function (creatinine ≤ 1.5 x laboratory ULN);
  13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  14. Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment (see section 4.3 for details). A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.

Exclusion Criteria:

  1. Previous treatment with trastuzumab or any other HER2/neu targeting antibody or agent;
  2. Continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 4 weeks prior to first dose of study treatment. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalents are permitted in the absence of active auto-immune disease;
  3. Prior organ transplant;
  4. Patient not considered a candidate for 5-FU, capecitabine, or cisplatin chemotherapy;
  5. History of documented congestive heart failure; angina pectoris requiring antianginal medication; evidence of transmural infarction on ECG; poorly controlled hypertension; clinically significant valvular heart disease; high risk uncontrolled arrhythmias; or New York Heart Association (NYHA) class II heart disease;
  6. If on warfarin (Coumadin®) or other vitamin K antagonists;
  7. Concurrent active malignancy except for adequately controlled limited basal cell carcinoma of the skin;
  8. Peripheral neuropathy or hearing loss of NCI CTCAE Grade > 2;
  9. History of uncontrolled seizures, central nervous disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent, participation in the study, or adversely affecting compliance to study drugs;
  10. Active infection requiring IV antibiotics;
  11. Positive for human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active hepatitis B (HBsAg reactive) or active hepatitis C (HCV ribonucleic acid [RNA] qualitative) infection;
  12. Pregnant or lactating females;
  13. Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic biopsy) within 1 week prior to study entry;
  14. Has received a live-virus vaccination within 4 weeks of first study vaccination. Seasonal flu vaccines that do not contain live virus are permitted;
  15. Current or recent (within 4 weeks of first IMU-131 vaccination) treatment with another investigational drug or participation in another investigational study.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02795988


Contacts
Contact: Anthony J Good, PhD +61 410 711 329 anthony.good@imugene.com

Locations
Hong Kong
Department of Medicine, Queen Mary Hospital Recruiting
Hong Kong, Hong Kong
Contact: Thomas Yau, MD         
Taiwan
National Cheng-Kung University Hospital Recruiting
Tainan, Taiwan, 704
Contact: Chia-Jui Yen, MD         
Taipei Veterans General Hospital Recruiting
Taipei, Taiwan, 11217
Contact: Yee Chao, MD         
Thailand
Immunology Unit, Research Division, National Cancer Institute Recruiting
Bangkok, Bankgkok, Thailand, 10400
Contact: Wirote Lausoontornsiri, MD         
Principal Investigator: Wirote Lausoontornsiri, MD         
Division of Medical Oncology, Department of Medicine, Prince of Songkla University, Songklanagarind Hospital Recruiting
Hat Yai, Songkhla Province, Thailand, 90110
Contact: Arunee Dechaphunkul, MD         
Principal Investigator: Arunee Dechaphunkul, MD         
Division of Medical Oncology, Department of Medicine, Chulalongkorn University Recruiting
Bangkok, Thailand, 10330
Contact: Suebpong Tansanvimon, MD         
Principal Investigator: Suebpong Tansanvimon, MD         
Oncology Unit, Department of Medicine, Rajavithi Hospital Recruiting
Bangkok, Thailand, 10400
Contact: Jedzada Maneechavakajorn, MD         
Principal Investigator: Jedzada Maneechavakajorn, MD         
Division of Oncology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University Recruiting
Chiang Mai, Thailand, 50200
Contact: Chaiyut Charoentum, MD         
Principal Investigator: Chaiyut Charoentum, MD         
Sponsors and Collaborators
Imugene Limited
Investigators
Principal Investigator: Christoph C Zielinski, MD, PhD Medical University Vienna - General Hospital
  More Information

Additional Information:
Responsible Party: Imugene Limited
ClinicalTrials.gov Identifier: NCT02795988     History of Changes
Other Study ID Numbers: IMU.ACS.001
First Submitted: June 1, 2016
First Posted: June 10, 2016
Last Update Posted: September 1, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Imugene Limited:
Secondary

Additional relevant MeSH terms:
Adenocarcinoma
Gastrointestinal Neoplasms
Digestive System Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Cisplatin
Capecitabine
Fluorouracil
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs