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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 : Active, not recruiting
First Posted : October 21, 2015
Last Update Posted : September 21, 2021
Sponsor:
Collaborator:
Varian
Information provided by (Responsible Party):
Maximilian Diehn, Stanford University

Tracking Information
First Submitted Date  ICMJE October 16, 2015
First Posted Date  ICMJE October 21, 2015
Last Update Posted Date September 21, 2021
Actual Study Start Date  ICMJE August 2016
Actual Primary Completion Date December 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2020)
  • 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 ]
    Dose limiting toxicity (DLT) is defined as the following grade 3; 4; or 5 CTCAE v4 events determined to be of possibly; probably; of definite relationship to treatment; occurring after 1st dose of fresolimumab and up to 30 days after the last dose of fresolimumab:
    1. Radiation pneumonitis, or
    2. Bronchopulmonary hemorrhage A safe dose of fresolimumab is reached when =< 10% of the patients receiving fresolimumab plus SABR develop DLTs.
  • Presence of late radiation induced fibrosis (Phase II) [ Time Frame: Up to 12 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
  • 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.
  • Presence of late radiation induced fibrosis (Phase II) [ Time Frame: Up to 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SABR-ATAC: A Trial of TGF-beta Inhibition and Stereotactic Ablative Radiotherapy for Early Stage Non-small Cell Lung Cancer
Official Title  ICMJE Fresolimumab and Stereotactic Ablative Radiotherapy in Early Stage Non-small Cell Lung Cancer
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.
Detailed Description

PRIMARY OBJECTIVES:

Phase 1: Evaluate the safe dose of fresolimumab in combination with stereotactic ablative radiotherapy (SABR) in patients.

Phase 2. Evaluate the rate of radiation induced pulmonary fibrosis after SABR plus fresolimumab.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Stage IA Non-Small Cell Lung Carcinoma
  • Stage IB Non-Small Cell Lung Carcinoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Treatment (fresolimumab, SABR)
In Phase 1: Patients receive fresolimumab IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12 in total of 5 subjects. In Phase 2: . Fresolimumab will be administered IV at the dose selected in the preceding Phase 1 on Days 1, 15 and 36 and SABR will be administered in 4 fractions between Days 8 and 12.
Interventions:
  • Biological: Fresolimumab
  • Other: Pharmacological Study
  • Radiation: Stereotactic Body Radiation Therapy
Publications * Not Provided

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 4, 2020)
24
Original Estimated Enrollment  ICMJE
 (submitted: October 19, 2015)
60
Estimated Study Completion Date  ICMJE December 2021
Actual Primary Completion Date December 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Patient judged to be inoperable or at high surgical risk by a board qualified thoracic cancer surgeon who has evaluated the subject within the prior 12 weeks, or the patient's case has been discussed at a multidisciplinary tumor board with a thoracic cancer surgeon in attendance, or a patient who refuses surgery or declines to be evaluated for surgery.
  • Able to give informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
  • 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)

Exclusion Criteria:

  • Significant anemia (hemoglobin below 9.0 g/dL) or neutropenia (absolute neutrophil count [ANC] < 1000/mm^3)
  • Prior history of multifocal adenocarcinoma in situ (ie, classic or pure bronchioloalveolar carcinoma)
  • Prior history of keratoacanthoma (well differentiated squamous cell skin cancer variant, often centrally ulcerated); history of basal cell cancer is allowed
  • Pre malignant skin lesion(s) noted on prescreening skin exam, except for actinic (solar) keratosis
  • Prior radiotherapy overlapping with high dose region of planned SABR course
  • Prior history of head and neck; oral; or bladder cancer
  • Prior receipt of systemic treatment (chemotherapy, targeted therapy, or immunotherapy) for the lesion under consideration of treatment
  • 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
  • Contraindication to receiving radiotherapy
  • Known allergy to components of fresolimumab
  • Pregnant or breastfeeding. 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.
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02581787
Other Study ID Numbers  ICMJE IRB-34863
NCI-2015-01726 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
LUN0071 ( Other Identifier: Stanford Cancer Institute )
IRB-34863 ( Other Identifier: Stanford IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Maximilian Diehn, Stanford University
Study Sponsor  ICMJE Maximilian Diehn
Collaborators  ICMJE Varian
Investigators  ICMJE
Principal Investigator: Maximilian Diehn Stanford Cancer Institute
PRS Account Stanford University
Verification Date September 2021

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