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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fresolimumab
Stereotactic Body Radiation Therapy
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage IA Non-Small Cell Lung Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Stanford University, School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

(Phase 1) Fresolimumab 3 mg/kg

(Phase 1) Fresolimumab 1 mg/kg

(Phase 2) Fresolimumab

Arm Description

Patients receive fresolimumab 3 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.

Patients receive fresolimumab 1 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.

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.

Outcomes

Primary Outcome Measures

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)
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: Radiation pneumonitis, or 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)

Secondary Outcome Measures

Full Information

First Posted
October 16, 2015
Last Updated
September 15, 2023
Sponsor
Stanford University
Collaborators
Varian Medical Systems
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1. Study Identification

Unique Protocol Identification Number
NCT02581787
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
August 2016 (Actual)
Primary Completion Date
March 2, 2023 (Actual)
Study Completion Date
March 2, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
Collaborators
Varian Medical Systems

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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. Phase 1: A cohort of 5 patients receive the pre-selected dose of 3mg/kg of fresolimumab. If one patient experiences a DLT, an additional 5 patients will be enrolled at 3 mg/kg. If no more patients experience a DLT, then 3 mg/kg will be the dose for the Phase 2 component. If 2 or more patients experience a DLT in the total expanded cohort (or 2 or more patients in the initial cohort experience DLT), then the investigational dose of fresolimumab will be changed to 1 mg/kg. If 2 or more patients in the initial cohort experience DLT before all 5 patients have been enrolled, the remaining patients will receive the lower dose of 1 mg/kg. Phase 2: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
(Phase 1) Fresolimumab 3 mg/kg
Arm Type
Experimental
Arm Description
Patients receive fresolimumab 3 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.
Arm Title
(Phase 1) Fresolimumab 1 mg/kg
Arm Type
Experimental
Arm Description
Patients receive fresolimumab 1 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.
Arm Title
(Phase 2) Fresolimumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Fresolimumab
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiation Therapy
Other Intervention Name(s)
SBRT
Intervention Description
Undergo SABR
Primary Outcome Measure Information:
Title
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)
Description
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: Radiation pneumonitis, or Bronchopulmonary hemorrhage A safe dose of fresolimumab is reached when =< 10% of the patients receiving fresolimumab plus SABR develop DLTs.
Time Frame
Up to 30 days
Title
Presence of late radiation induced fibrosis (Phase II)
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maximilian Diehn
Organizational Affiliation
Stanford Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University, School of Medicine
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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