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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Transgene
Sponsor:
Information provided by (Responsible Party):
Transgene
ClinicalTrials.gov Identifier:
NCT01383148
First received: June 23, 2011
Last updated: July 15, 2014
Last verified: July 2014
  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.


Condition Intervention Phase
Non-Small-Cell Lung Carcinoma
Biological: TG4010
Drug: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Transgene:

Primary Outcome Measures:
  • Phase 2: Progression-free Survival (PFS) [ Time Frame: Approximately 15 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    OS is measured from date of randomization to date of death from any cause.


Secondary Outcome Measures:
  • Phase 2 : Overall Survival (OS) [ Time Frame: Approximately 15 months ] [ Designated as safety issue: No ]
  • Phase 2 : Overall Response Rate (ORR) [ Time Frame: Approximately 15 months ] [ Designated as safety issue: No ]
  • Phase 3: Progression-free Survival (PFS) [ Time Frame: Approximately 27 months ] [ Designated as safety issue: No ]
  • Phase 3 : Overall Response Rate (ORR) [ Time Frame: Approximately 27 months ] [ Designated as safety issue: No ]
  • Phase 2 : Duration of response [ Time Frame: Approximately 15 months ] [ Designated as safety issue: No ]
  • Phase 2: Safety [ Time Frame: Approximately 15 months ] [ Designated as safety issue: Yes ]
  • Phase 3: Duration of response [ Time Frame: Approximately 27 months ] [ Designated as safety issue: No ]
  • Phase 3: Safety [ Time Frame: Approximately 27 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1000
Study Start Date: April 2012
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 - TG4010 + first line therapy
First-line therapy and maintenance therapy
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.

Active Comparator: Arm 2 : Placebo + first line therapy
First-line therapy and maintenance therapy
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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).
  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: NCT01383148

  Show 72 Study Locations
Sponsors and Collaborators
Transgene
Investigators
Principal Investigator: QUOIX Elisabeth, Prof Hôpitaux Universitaires de Strasbourg
  More Information

Additional Information:
NSCLC  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Transgene
ClinicalTrials.gov Identifier: NCT01383148     History of Changes
Other Study ID Numbers: TG4010.14/TIME, 8559
Study First Received: June 23, 2011
Last Updated: July 15, 2014
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration

Keywords provided by Transgene:
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Bevacizumab
Carboplatin
Paclitaxel
Pemetrexed
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Folic Acid Antagonists
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014