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.
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
Drug | Synonyms | Arms |
---|
Fresolimumab | 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 | Treatment (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
Name | Type | Description | Interventions |
---|
Treatment (fresolimumab, SABR) | Experimental | Patients 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