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

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ClinicalTrials.gov Identifier: NCT02581787
Recruitment Status : Recruiting
First Posted : October 21, 2015
Last Update Posted : February 5, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Maximilian Diehn, Stanford University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Stage IA Non-Small Cell Lung Carcinoma Stage IB Non-Small Cell Lung Carcinoma Biological: Fresolimumab Other: Pharmacological Study Radiation: Stereotactic Body Radiation Therapy Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Fresolimumab and Stereotactic Ablative Radiotherapy in Early Stage Non-small Cell Lung Cancer
Actual Study Start Date : August 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2020


Arm Intervention/treatment
Experimental: Treatment (fresolimumab, SABR)
Patients receive fresolimumab IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.
Biological: Fresolimumab
Given IV
Other Names:
  • Anti-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, Dimer

Other: Pharmacological Study
Correlative studies

Radiation: Stereotactic Body Radiation Therapy
Undergo SABR
Other Name: SBRT




Primary Outcome Measures :
  1. 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 ]
    A safe dose of fresolimumab is reached when =< 10% of the patients receiving fresolimumab plus SABR develop DLTs.

  2. Presence of late radiation induced fibrosis (Phase II) [ Time Frame: Up to 12 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02581787


Locations
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United States, California
Stanford University, School of Medicine Recruiting
Palo Alto, California, United States, 94304
Contact: Rachel Freilberg    650-725-0438    rachelf@stanford.edu   
Principal Investigator: Maximilian Diehn         
Principal Investigator: Bill Loo         
Principal Investigator: Joel Neal         
Sponsors and Collaborators
Maximilian Diehn
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Maximilian Diehn Stanford Cancer Institute

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Responsible Party: Maximilian Diehn, Assistant Professor of Radiation Oncology, Stanford University
ClinicalTrials.gov Identifier: NCT02581787     History of Changes
Other Study ID Numbers: LUN0071
NCI-2015-01726 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
4593
LUN0071 ( Other Identifier: Stanford Cancer Institute )
P30CA124435 ( U.S. NIH Grant/Contract )
First Posted: October 21, 2015    Key Record Dates
Last Update Posted: February 5, 2019
Last Verified: February 2019
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents