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SABR-ATAC: A Trial of TGF-beta Inhibition and Stereotactic Ablative Radiotherapy for Early Stage Non-small Cell Lung Cancer

NCT02581787

Description:

The SABR-ATAC trial (Stereotactic Ablative Radiotherapy and anti-TGFB Antibody Combination) is a phase I/II trial that studies the side effects and efficacy of fresolimumab, an anti-transforming growth factor beta (TGFB) antibody, when given with stereotactic ablative radiotherapy in patients with stage IA-IB non-small cell lung cancer. Fresolimumab may inhibit radiation side effects and block tumor growth through multiple mechanisms. Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy (SBRT), is a specialized form of radiation therapy that precisely delivers high dose radiation directly to tumors, thus killing tumor cells and minimizing damage to normal tissue. Giving fresolimumab with SABR may work better in treating patients with early stage non-small cell lung cancer than treating with SABR alone.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: SABR-ATAC: A Trial of TGF-beta Inhibition and Stereotactic Ablative Radiotherapy for Early Stage Non-small Cell Lung Cancer
  • Official Title: Fresolimumab and Stereotactic Ablative Radiotherapy in Early Stage Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: LUN0071
  • SECONDARY ID: NCI-2015-01726
  • SECONDARY ID: 4593
  • SECONDARY ID: LUN0071
  • SECONDARY ID: P30CA124435
  • NCT ID: NCT02581787

Conditions

  • Stage IA Non-Small Cell Lung Carcinoma
  • Stage IB Non-Small Cell Lung Carcinoma

Interventions

DrugSynonymsArms
FresolimumabAnti-TGF-Beta Monoclonal Antibody GC1008, GC1008, Human Anti-TGF-Beta Monoclonal Antibody GC1008, Immunoglobulin G4, anti-(transforming growth factor beta) (human monoclonal GC-1008 heavy chain), disulfide with human monoclonal GC-1008 light chain, DimerTreatment (fresolimumab, SABR)

Purpose

The SABR-ATAC trial (Stereotactic Ablative Radiotherapy and anti-TGFB Antibody Combination) is a phase I/II trial that studies the side effects and efficacy of fresolimumab, an anti-transforming growth factor beta (TGFB) antibody, when given with stereotactic ablative radiotherapy in patients with stage IA-IB non-small cell lung cancer. Fresolimumab may inhibit radiation side effects and block tumor growth through multiple mechanisms. Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy (SBRT), is a specialized form of radiation therapy that precisely delivers high dose radiation directly to tumors, thus killing tumor cells and minimizing damage to normal tissue. Giving fresolimumab with SABR may work better in treating patients with early stage non-small cell lung cancer than treating with SABR alone.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Evaluate the safe dose of fresolimumab in combination with stereotactic ablative
      radiotherapy (SABR) in patients. (Phase I) II. Evaluate the rate of radiation induced
      pulmonary fibrosis after SABR plus fresolimumab. (Phase II)

      SECONDARY OBJECTIVES:

      I. Evaluate potential adverse events in patients receiving fresolimumab plus SABR. (Phase I)
      II. Evaluate post treatment changes in pulmonary function. (Phase I) III. Evaluate
      recurrence rates and progression free survival. (Phase I) IV. Assess pharmacokinetics (PK)
      of fresolimumab in combination with SABR (optional for patient). (Phase I) V. Evaluate the
      rate and severity of radiation induced pulmonary fibrosis after SABR plus fresolimumab.
      (Phase I) VI. Evaluate the severity of radiation induced pulmonary fibrosis after SABR plus
      fresolimumab. (Phase II) VII. Evaluate potential adverse events in patients receiving
      fresolimumab plus SABR. (Phase II) VIII. Evaluate post treatment changes in pulmonary
      function. (Phase II) IX. Evaluate recurrence rates and progression free survival. (Phase II)

      OUTLINE: This is a phase I, dose escalation study of fresolimumab followed by a phase II
      study.

      Patients receive fresolimumab intravenously (IV) on days 1, 15, and 36 and undergo SABR in 4
      fractions between days 8 and 12.

      After completion of study treatment, patients are followed up at 3, 6, and 12 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (fresolimumab, SABR)ExperimentalPatients receive fresolimumab IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Newly diagnosed, histologically proven (or strongly suspected, see below) T1-T2aN0M0
                 (Stage IA-IB) non-small cell lung cancer (NSCLC), with maximum tumor diameter =< 5 cm
                 under consideration for stereotactic ablative body radiotherapy (SABR) as definitive
                 primary treatment
    
              -  Pathologic confirmation of NSCLC diagnosis is recommended whenever possible; this
                 will generally be accomplished using computed tomography (CT) guided or bronchoscopic
                 biopsies; if pathologic confirmation is not possible, a target lesion must be a non
                 calcified pulmonary nodule that is present on at least 2 imaging studies (can include
                 simulation scan); the nodule must have increased in size or proportion of solid
                 component on CT and/or show increased fluorodeoxyglucose (FDG) uptake on positron
                 emission tomography (PET) over at least 2 imaging studies
    
              -  No history of prior radiotherapy overlapping with high dose region of planned SABR
                 course
    
              -  No prior receipt of systemic treatment (chemotherapy, targeted therapy, or
                 immunotherapy) for the lesion under consideration of treatment
    
              -  No uncontrolled, inter-current or recent illness that in the investigator's opinion
                 precludes participation in the study, including those undergoing therapy for a
                 separate invasive malignancy
    
              -  Able to give informed consent
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
    
            Exclusion Criteria:
    
              -  No significant anemia (hemoglobin below 9.0 g/dL) or neutropenia (absolute neutrophil
                 count [ANC] < 1000/mm^3)
    
              -  No prior history of lung resection on ipsilateral side
    
              -  No prior history of multifocal adenocarcinoma in situ (ie, classic or pure
                 bronchioloalveolar carcinoma)
    
              -  No prior history of idiopathic pulmonary fibrosis
    
              -  No prior history of keratoacanthoma (well differentiated squamous cell skin cancer
                 variant, often centrally ulcerated); history of basal cell cancer is allowed
    
              -  No contraindication to receiving radiotherapy and no known allergy to components of
                 fresolimumab
    
              -  No pregnant or breastfeeding women; men or women of child bearing potential must
                 agree to use an acceptable method of birth control (hormonal or barrier method of
                 birth control; abstinence) to avoid pregnancy for at least 90 days after last study
                 treatment (radiation or fresolimumab); all women of child bearing potential (last
                 menstrual period within the previous 12 months and not surgically sterile) will be
                 tested for pregnancy at pre-entry
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Dose limiting toxicities (DLTs) of fresolimumab when combined with SABR defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher radiation pneumonitis or bronchopulmonary hemorrhage (Phase I)
    Time Frame:Up to 30 days
    Safety Issue:
    Description:A safe dose of fresolimumab is reached when =< 10% of the patients receiving fresolimumab plus SABR develop DLTs.

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Maximilian Diehn

    Last Updated

    September 13, 2016