Evaluation of an Anti-cancer Immunotherapy Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer (INDUCT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01220128
First received: October 7, 2010
Last updated: September 4, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the safety, immunogenicity and clinical activity of a new WT1 anti-cancer immunotherapy in patients with WT1-positive Stage II or III breast cancer. The treatment will be given before surgery in combination with standard therapy.


Condition Intervention Phase
Neoplasms, Breast
Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study of GSK2302024A Antigen-Specific Cancer Immunotherapeutic Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Phase I segment of the study: occurrence of severe toxicities. [ Time Frame: On a continuous basis during the whole study duration (Day 0 to 36 months after concluding visit-30 days post-surgery). ] [ Designated as safety issue: No ]
  • Phase I segment of the study: immunogenicity to constituent of the investigational immunotherapy. [ Time Frame: Post study treatment Dose 4, evaluated using a blood sample collected at Visit 5, after 13 weeks of treatment. ] [ Designated as safety issue: No ]
  • Phase II segment of the study: occurrence of severe toxicities. [ Time Frame: On a continuous basis during the whole study duration (Day 0 to 36 months after concluding visit). ] [ Designated as safety issue: No ]
  • Phase II segment of the study: occurrence of adverse events and serious adverse events. [ Time Frame: On a continuous basis during the study treatment period and ending 30 days after the last study treatment administration (Week 16 or 22 depending on the chemotherapy regimen). ] [ Designated as safety issue: No ]
  • Phase II segment of the study: occurrence of serious adverse events related to study treatment. [ Time Frame: On a continuous basis during the whole study duration (Day 0 to 36 months after concluding visit). ] [ Designated as safety issue: No ]
  • Phase II segment of the study: Immunogenicity to constituent of the investigational immunotherapy. [ Time Frame: At treatment start, after 10, 13 and 16 weeks of treatment, or after 10, 13, 19 and 22 weeks of treatment depending on the treatment regimen, at concluding Visit, as well as after 6 and 12 months after concluding visit. ] [ Designated as safety issue: No ]
  • Phase II segment of the study: clinical activity (The pathological response in the breast and axillary nodes at the definitive surgery). [ Time Frame: At surgery (pathological complete response). ] [ Designated as safety issue: No ]
  • Phase II segment of the study: other indicators of clinical activity (Disease free survival and Overall survival). [ Time Frame: From surgery onwards until the end of the post study contact (6 years after the concluding visit). ] [ Designated as safety issue: No ]

Estimated Enrollment: 250
Study Start Date: April 2011
Estimated Study Completion Date: November 2022
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Postmenopausal patients with hormone receptor-positive breast cancer who will receive a specific, indicated standard therapy combined with the investigational treatment
Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A
6 or 8 injections
Placebo Comparator: Group B
Postmenopausal patients with hormone receptor-positive breast cancer who will receive a specific, indicated standard therapy combined with placebo
Biological: Placebo
6 or 8 injections
Experimental: Group C
Patients who will receive another specific, indicated standard therapy (chemotherapy) combined with the investigational treatment
Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A
6 or 8 injections
Placebo Comparator: Group D
Patients who will receive another specific, indicated standard therapy (chemotherapy) combined with placebo
Biological: Placebo
6 or 8 injections
Experimental: Group E
Patients with HER2-overexpressing breast cancer who will receive a third kind of specific, indicated standard therapy (Trastuzumab) combined with the investigational treatment
Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A
6 or 8 injections
Placebo Comparator: Group F
Patients with HER2-overexpressing breast cancer who will receive a third kind of specific, indicated standard therapy (Trastuzumab) combined with placebo
Biological: Placebo
6 or 8 injections
Experimental: Group G
Patients with hormone receptor-positive and HER2 non-overexpressing breast cancer who will receive neoadjuvant chemotherapy combined with the investigational treatment
Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A
6 or 8 injections
Experimental: Group H
Patients with hormone receptor-positive and HER2 non-overexpressing breast cancer who will receive neoadjuvant chemotherapy combined with the investigational treatment
Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2302024A
6 or 8 injections
Placebo Comparator: Group I
Patients with hormone receptor-positive and HER2 non-overexpressing breast cancer who will receive neoadjuvant chemotherapy combined with placebo
Biological: Placebo
6 or 8 injections

Detailed Description:

The study will be conducted in two consecutive segments (Phase I and Phase II), each with specific objectives. Active follow-up will be for three years.

The protocol has been updated following Protocol Amendment 4, April 2013, leading to the update of the study design.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient is ≥ 18 years of age at the time the informed consent to screening has been obtained.
  • The patient has proven T1 with lymph node involvement or T2-T4c, any N, M0 primary invasive breast cancer, histologically confirmed by core needle biopsy.

Isolated supraclavicular lymph node involvement is allowed.

  • The patient's tumor shows WT1 antigen expression.
  • The patient has one of the following histologically confirmed breast cancer subtypes:

    • Estrogen receptor and/or progesterone positive tumor.
    • Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer.
    • HER2-negative breast cancer.
  • Eastern Cooperative Oncology Group (performance status of 0 or 1 at the time of study treatment allocation.
  • Baseline left ventricular ejection fraction of ≥ 50% as measured within six weeks prior to study treatment allocation by echocardiography or multi-gated acquisition(MUGA)scan.
  • The patient shows normal organ function according to the following parameters(as measured within six weeks prior to treatment allocation)::

    • Hemoglobin: Within normal range according to institutional standards.
    • Absolute leukocyte count: Within normal range according to institutional standards.
    • Absolute lymphocyte count: Within normal range according to institutional standards.
    • Platelet count: Within normal range according to institutional standards
    • Alanine aminotransferase: ≤ 2.5 x Upper Limit of Normal (ULN)
    • Aspartate aminotransferase: ≤ 2.5 x ULN
    • Total bilirubin: ≤ 1.5 x ULN. In the case of known Gilbert's syndrome ≤ 2 x ULN
    • Serum creatinine: 1.5 x ULN
    • Calculated creatinine clearance: > 50 mL/min
  • A female patient of childbearing potential may be enrolled in the study, if the patient:

    • has practiced adequate contraception for 30 days prior to study product administration, and
    • has a negative pregnancy test within one week prior to treatment allocation and
    • has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the study product administration series.In view of the investigator, the patient can and will comply with the requirements of the protocol.
  • Written informed consent has been obtained from the patient prior to performance of any study specific procedure.

Exclusion Criteria:

  • The patient has inflammatory breast cancer, which is defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion.
  • Diagnosis established by incisional biopsy.
  • Prior and concomitant neoadjuvant anti-breast-cancer treatments such as chemotherapy, immunotherapy / biological response modifiers, endocrine therapy, and radiotherapy, unless authorized specifically by the protocol.
  • The patient is known to be human immunodeficiency virus -positive.
  • The patient has symptomatic autoimmune disease such as, but not limited to multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
  • The patient is known to have difficult-to-control hypertension, coronary artery disease, arrhythmia requiring treatment, clinically significant valvular disease, cardiomegaly on chest X-ray, ventricular hypertrophy on electrocardiogram or previous myocardial infarction or congestive heart failure.
  • The patient has a history of allergic reactions likely to be exacerbated by any component of the investigational product used in the study.
  • The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
  • The patient has (or has had) previous or concomitant malignancies at other sites, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
  • The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the study procedures.
  • The patient has received any investigational or non-registered product within 30 days preceding the first dose of study products or planned use during the study period.
  • The patient requires concomitant treatment with any immunosuppressive agents or with systemic corticosteroids prescribed for chronic treatment.
  • The patient has a significant disorder of coagulation or receives treatment with warfarin derivatives or heparin. Patients receiving individual doses of low molecular weight heparin outside of 24 hours prior to WT1-A10 + AS15 ASCI/placebo administration are eligible. Patients receiving prophylactic antiplatelet medications e.g. low-dose aspirin, and without a clinically-apparent bleeding tendency are eligible.
  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: NCT01220128

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 51 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01220128     History of Changes
Other Study ID Numbers: 113172, 2010-019909-42
Study First Received: October 7, 2010
Last Updated: September 4, 2014
Health Authority: Italy: Isituto Superiore di Sanita'
Belgium: Federal Agency for Medicines and Health Products, FAMHP
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United States: Food and Drug Administration
Denmark: Lægemiddelstyrelsen
Canada: Health Canada
Germany: Paul-Ehrlich-Institut

Keywords provided by GlaxoSmithKline:
WT1
neoadjuvant
tumor antigen
immunotherapy
breast cancer
adult

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on September 16, 2014