Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma
Conditions
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.
Interventions
BIOLOGICALFresolimumab
Given IV
RADIATIONStereotactic Body Radiation Therapy
Undergo SABR
Sponsors
Varian Medical Systems
Maximilian Diehn
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Dose Limiting Toxicities (DLTs) of Fresolimumab When Combined With SABR (Phase I) | Up to 30 days | DLT is defined as CTCAE grade 3 or higher radiation pneumonitis or bronchopulmonary hemorrhage. |
| Number of Participants With Late Radiation Induced Fibrosis | 12 months | Presence of radiation induced pulmonary fibrosis is defined as presence of a moderate-to-severe level of fibrosis. This outcome is primary in phase 2 patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Late Radiation Induced Fibrosis (Phase 1 Patients) | 12 months | Presence of radiation induced pulmonary fibrosis is defined as presence of a moderate-to-severe level of fibrosis. This outcome is secondary for phase 1 patients. |
Countries
United States
Participant flow
Pre-assignment details
28 participants signed consent; 24 were allocated to treatment.
Participants by arm
| Arm | Count |
|---|---|
| (Phase 1) Fresolimumab 3 mg/kg Patients receive fresolimumab 3 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12. | 5 |
| (Phase 2) Fresolimumab 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. | 19 |
| Total | 24 |
Baseline characteristics
| Characteristic | (Phase 1) Fresolimumab 3 mg/kg | (Phase 2) Fresolimumab | Total |
|---|---|---|---|
| Age, Customized 50-59 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized 60-69 years | 2 Participants | 4 Participants | 6 Participants |
| Age, Customized 70-79 years | 3 Participants | 9 Participants | 12 Participants |
| Age, Customized 80-89 years | 0 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 19 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 14 Participants | 19 Participants |
| Region of Enrollment United States | 5 Participants | 19 Participants | 24 Participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 11 Participants |
| Sex: Female, Male Male | 2 Participants | 11 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 5 | 5 / 19 |
| other Total, other adverse events | 5 / 5 | 15 / 19 |
| serious Total, serious adverse events | 0 / 5 | 6 / 19 |
Outcome results
Primary
Number of Participants Experiencing Dose Limiting Toxicities (DLTs) of Fresolimumab When Combined With SABR (Phase I)
DLT is defined as CTCAE grade 3 or higher radiation pneumonitis or bronchopulmonary hemorrhage.
Time frame: Up to 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| (Phase 1) Fresolimumab 3 mg/kg | Number of Participants Experiencing Dose Limiting Toxicities (DLTs) of Fresolimumab When Combined With SABR (Phase I) | 0 Participants |
Primary
Number of Participants With Late Radiation Induced Fibrosis
Presence of radiation induced pulmonary fibrosis is defined as presence of a moderate-to-severe level of fibrosis. This outcome is primary in phase 2 patients.
Time frame: 12 months
Population: Patients who met criteria to be considered for endpoint analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| (Phase 1) Fresolimumab 3 mg/kg | Number of Participants With Late Radiation Induced Fibrosis | 5 Participants |
Secondary
Number of Participants With Late Radiation Induced Fibrosis (Phase 1 Patients)
Presence of radiation induced pulmonary fibrosis is defined as presence of a moderate-to-severe level of fibrosis. This outcome is secondary for phase 1 patients.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| (Phase 1) Fresolimumab 3 mg/kg | Number of Participants With Late Radiation Induced Fibrosis (Phase 1 Patients) | 1 Participants |