Clinical Trials /

Phase IIB/III Of TG4010 Immunotherapy In Patients With Stage IV Non-Small Cell Lung Cancer

NCT01383148

Description:

This is a Phase IIb/III randomized, double-blind, placebo-controlled study to compare the efficacy and safety of first-line therapy combined with TG4010 or placebo in stage IV non-small cell lung cancer (NSCLC). TG4010 is a suspension of recombinant Modified Vaccinia virus strain Ankara (MVA strain) carrying coding sequences for human MUC1 antigen and human interleukin-2 (IL2). TG4010 has been developed for use as an immunotherapy in cancer patients whose tumors express the MUC1 antigen. TG4010 is intended to induce a MUC1-specific cellular immune response and to produce a non-specific activation of several components of the immune system.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Phase IIB/III Of TG4010 <span class="go-doc-concept go-doc-intervention">Immunotherapy</span> In Patients With Stage IV Non-Small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: Phase IIB/III Of TG4010 Immunotherapy In Patients With Stage IV Non-Small Cell Lung Cancer
  • Official Title: A Phase IIB/III Randomized, Double-blind, Placebo Controlled Study Comparing First Line Therapy With or Without TG4010 Immunotherapy Product in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)
  • Clinical Trial IDs

    NCT ID: NCT01383148

    ORG ID: TG4010.14/TIME

    NCI ID: 8559

    Trial Conditions

    Non-Small-Cell Lung Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    placebo paclitaxel, carboplatin, pemetrexed, cisplatin, gemcitabine, bevacizumab (if prescribed), erlotinib Arm 2 : Placebo + first line therapy

    Trial Purpose

    This is a Phase IIb/III randomized, double-blind, placebo-controlled study to compare the
    efficacy and safety of first-line therapy combined with TG4010 or placebo in stage IV
    non-small cell lung cancer (NSCLC).

    TG4010 is a suspension of recombinant Modified Vaccinia virus strain Ankara (MVA strain)
    carrying coding sequences for human MUC1 antigen and human interleukin-2 (IL2). TG4010 has
    been developed for use as an immunotherapy in cancer patients whose tumors express the MUC1
    antigen.

    TG4010 is intended to induce a MUC1-specific cellular immune response and to produce a
    non-specific activation of several components of the immune system.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm 1 - TG4010 + first line therapy Experimental First-line therapy and maintenance therapy
    Arm 2 : Placebo + first line therapy Active Comparator First-line therapy and maintenance therapy placebo

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, large cell
    carcinoma, undifferentiated carcinoma or other)

    - Stage IV cancer according to TNM classification (7th edition - UICC, December 2009;
    includes tumor with malignant pleural or pericardial effusion

    - Tumor biopsy specimen with 50% of MUC1 expressing tumor cells determined by
    Immunohistochemistry (IHC) staining on fixed pathological material. Biopsy may come
    either from the primary tumor or from a metastasis. Cytological material is not
    accepted for this analysis

    - Patient's nave to first-line therapy for the advanced stage of the disease. Previous
    neoadjuvant or adjuvant therapy is allowed for patients who successfully underwent
    complete radical surgery and if last treatment was administered more than 12 months
    prior to the start of the study treatment, i.e., D1 of Cycle 1.

    - At least one measurable lesion by CT scan or MRI based on RECIST version 1.1

    - PS 0 or 1 on the ECOG scale

    - Adequate hematological, hepatic, and renal function:

    - Hemoglobin 10.0 g/dL

    - White Blood Cells (WBC) 3.0x10E9/L including

    - Neutrophils 1.5x109/L

    - Total lymphocytes count 0.5x10E9/L

    - Platelets count 100x10E9/L

    - Serum alkaline phosphatase 3x ULN (upper limit of normal)in the absence of
    liver or bone metastases or 5 ULN(in patients with documented bone or liver
    metastases)

    - Serum transaminases (alanine aminotransferase [ALT] and aspartate
    aminotransferase [AST]) 2.5 x ULN in the absence of liver metastases or =< 5
    ULN in case of liver metastases)

    - Total bilirubin 1.5 x ULN

    - Glomerular Filtration Rate 60 mL/min (according to Modification of the Diet in
    Renal Disease (MDRD) formula or cockroft & Gault formula)

    - Serum albumin 30 g/L

    - Effective contraception during the study period and for 3 months after the last
    study treatment administration (male and female patient)

    Exclusion Criteria:

    - Patients having Central Nervous System (CNS) metastases. Patients who have had brain
    metastases surgically removed or irradiated with no residual disease confirmed by
    imaging are allowed

    - Documented EGFR activating mutations (if already tested)

    - Prior history of other malignancy except:

    - Basal cell carcinoma of the skin

    - Cervical intra epithelial neoplasia

    - Other cancer curatively treated with no evidence of disease for at least 5 years

    - Patients under chronic treatment with systemic corticoids or other immunosuppressive
    drugs (e.g., cyclosporine) for a period of at least 4 weeks and whose treatment was
    not stopped 1 week prior to the start of the study treatment (i.e., D1 of Cycle 1)

    - Positive serology for Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV);
    presence in the serum of the antigens HBs

    - Patient with any underlying medical condition that the treating physician considers
    might be aggravated by treatment or which is not controlled (e.g., elevated troponin
    or creatinine, uncontrolled diabetes)

    - Patient with major surgery or radiotherapy within 4 weeks prior to the start of the
    study treatment (i.e., D1 of Cycle 1). Prior surgery or radiation therapy aimed at
    local palliation or attempted local disease control is permitted

    - Patient with an organ allograft

    - Known allergy to eggs, gentamicin or platinum-containing compounds

    - Participation in a clinical study with an investigational product within 4 weeks
    prior to the start of the study treatment (i.e., D1 of Cycle 1)

    - Patient unable or unwilling to comply with the protocol requirements

    - Pregnancy or lactation

    - Bevacizumab will be allowed for patients with non-squamous carcinoma. Prescribing
    information must be followed and precautions have to be taken into consideration
    (e.g., patients having presented a serious hemorrhage or recent hemoptysis should not
    receive bevacizumab).

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Phase 2: Progression-free Survival (PFS)

    Phase 3: Overall Survival (OS)

    Secondary Outcome Measures

    Phase 2 : Overall Survival (OS)

    Phase 2 : Overall Response Rate (ORR)

    Phase 3: Progression-free Survival (PFS)

    Phase 3 : Overall Response Rate (ORR)

    Phase 2 : Duration of response

    Phase 2: Safety

    Phase 3: Duration of response

    Phase 3: Safety

    Trial Keywords

    NSCLC