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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01383148
Recruitment Status : Terminated
First Posted : June 28, 2011
Last Update Posted : January 5, 2017
Sponsor:
Information provided by (Responsible Party):
Transgene

Tracking Information
First Submitted Date  ICMJE June 23, 2011
First Posted Date  ICMJE June 28, 2011
Last Update Posted Date January 5, 2017
Study Start Date  ICMJE April 2012
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2011)
  • Phase 2: Progression-free Survival (PFS) [ Time Frame: Approximately 15 months ]
    PFS is measured from date of randomization to radiographically documented progression according to RECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.
  • Phase 3: Overall Survival (OS) [ Time Frame: Approximately 27 months ]
    OS is measured from date of randomization to date of death from any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: June 27, 2011)
PFS [ Time Frame: 9 months ]
Progression-free Survival
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2012)
  • Phase 2 : Overall Survival (OS) [ Time Frame: Approximately 15 months ]
  • Phase 2 : Overall Response Rate (ORR) [ Time Frame: Approximately 15 months ]
  • Phase 3: Progression-free Survival (PFS) [ Time Frame: Approximately 27 months ]
  • Phase 3 : Overall Response Rate (ORR) [ Time Frame: Approximately 27 months ]
  • Phase 2 : Duration of response [ Time Frame: Approximately 15 months ]
  • Phase 2: Safety [ Time Frame: Approximately 15 months ]
  • Phase 3: Duration of response [ Time Frame: Approximately 27 months ]
  • Phase 3: Safety [ Time Frame: Approximately 27 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2011)
  • OS [ Time Frame: 9 months ]
    • Overall Survival (OS)
  • ORR [ Time Frame: 9 months ]
    • Overall Response Rate (ORR)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase IIB/III Of TG4010 Immunotherapy In Patients With Stage IV Non-Small Cell Lung Cancer
Official Title  ICMJE 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)
Brief Summary

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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Non-Small-Cell Lung Carcinoma
Intervention  ICMJE
  • Biological: TG4010

    TG4010 • TG4010 will be administered starting on Day 1 (D1) of Cycle 1 of chemotherapy and will be administered weekly for 6 weeks by subcutaneous (SC) injections and then once every 3 weeks until progression or discontinuation due to any reason.

    Chemotherapy (and bevacizumab if prescribed), will be given as 21-day cycles for a minimum of 4 cycles and up to 6 cycles.

    First line therapy:

    • Non-squamous carcinoma: pemetrexed + cisplatin or paclitaxel + carboplatin +/- bevacizumab
    • Squamous carcinoma: gemcitabine + cisplatin or paclitaxel + carboplatin

    Maintenance therapy:

    • Pemetrexed or erlotinib for eligible patients and according to labeling.

  • Drug: placebo

    Placebo will be administered starting on D1 of Cycle 1 of chemotherapy and will be administered weekly for 6 weeks by SC injections and then once every 3 weeks until progression or discontinuation due to any reason.

    • First line therapy: as in Arm 1
    • Maintenance therapy: as in Arm 1
    Other Names:
    • paclitaxel
    • carboplatin
    • pemetrexed
    • cisplatin
    • gemcitabine
    • bevacizumab (if prescribed)
    • erlotinib
Study Arms  ICMJE
  • Experimental: Arm 1 - TG4010 + first line therapy
    First-line therapy and maintenance therapy
    Intervention: Biological: TG4010
  • Active Comparator: Arm 2 : Placebo + first line therapy
    First-line therapy and maintenance therapy
    Intervention: Drug: placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 4, 2017)
222
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2011)
1000
Actual Study Completion Date  ICMJE July 2016
Actual Primary Completion Date July 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 naïve 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Hungary,   Israel,   Italy,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01383148
Other Study ID Numbers  ICMJE TG4010.14/TIME
8559 ( Other Identifier: FDA )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Transgene
Study Sponsor  ICMJE Transgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: QUOIX Elisabeth, Prof Hôpitaux Universitaires de Strasbourg
PRS Account Transgene
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP