Stage IA Non-Small Cell Lung CarcinomaPhase 1/2NCT02581787

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

A Phase 1/2 study testing Fresolimumab and Stereotactic Body Radiation Therapy in people with Stage IA Non-Small Cell Lung Carcinoma and Stage IB Non-Small Cell Lung Carcinoma, run by Maximilian Diehn at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma
What is being tested?: Fresolimumab and Stereotactic Body Radiation Therapy
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 1 siteUnited States
Study dates: Aug 2016to 2 Mar 2023
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Show all 11Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Stanford University, School of Medicine
Palo Alto, California, 94304

Other trials in United States

About this study

Official title: Fresolimumab and Stereotactic Ablative Radiotherapy in Early Stage Non-small Cell Lung Cancer

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.

Read the 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:

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.

Conditions: Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma
Being tested: Fresolimumab, Stereotactic Body Radiation Therapy
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FresolimumabBiological
Also called 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
Given IV
Stereotactic Body Radiation TherapyRadiation
Also called SBRT
Undergo SABR

Study groups in NCT02581787
Study group	Role	What they receive
(Phase 1) Fresolimumab 3 mg/kg	Experimental	Patients receive fresolimumab 3 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12. Receives: Biological: Fresolimumab; Radiation: Stereotactic Body Radiation Therapy
(Phase 1) Fresolimumab 1 mg/kg	Experimental	Patients receive fresolimumab 1 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12. Receives: Biological: Fresolimumab; Radiation: Stereotactic Body Radiation Therapy
(Phase 2) Fresolimumab	Experimental	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. Receives: Biological: Fresolimumab; Radiation: Stereotactic Body Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Up to 30 days
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.
Measured: 12 months

Secondary outcomes (1)

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.
Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 20162 Mar 2023

First posted21 Oct 2015 (estimated)
Study startAug 2016
Primary completion2 Mar 2023
Study completion2 Mar 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Stage IA Non-Small Cell Lung CarcinomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02581787
Sponsor's protocol ID: IRB-34863
Other IDs: NCI-2015-01726, LUN0071, IRB-34863
Status last verified: Mar 2024
First submitted: 16 Oct 2015
Last updated: 27 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Stage IA Non-Small Cell Lung Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Fresolimumab and Stereotactic Ablative Radiotherapy in Early Stage Non-small Cell Lung Cancer
ClinicalTrials.gov ID: NCT02581787
Acronym / sponsor ID: IRB-34863
Conditions: Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Maximilian DiehnUniversity, hospital or other
Collaborators: Varian Medical Systems
Study start: Aug 2016 (actual)
Primary completion: 2 Mar 2023 (actual)
Study completion: 2 Mar 2023 (actual)
First posted: 21 Oct 2015 (estimated)
Results: Posted 27 Mar 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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:

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
(Phase 1) Fresolimumab 3 mg/kg	Experimental	Biological: Fresolimumab, Radiation: Stereotactic Body Radiation TherapyPatients receive fresolimumab 3 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.
(Phase 1) Fresolimumab 1 mg/kg	Experimental	Biological: Fresolimumab, Radiation: Stereotactic Body Radiation TherapyPatients receive fresolimumab 1 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.
(Phase 2) Fresolimumab	Experimental	Biological: Fresolimumab, Radiation: Stereotactic Body Radiation TherapyFresolimumab 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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)

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FresolimumabAlso: 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, DimerGiven IV	Biological	(Phase 1) Fresolimumab 1 mg/kg, (Phase 1) Fresolimumab 3 mg/kg, (Phase 2) Fresolimumab
Stereotactic Body Radiation TherapyAlso: SBRTUndergo SABR	Radiation	(Phase 1) Fresolimumab 1 mg/kg, (Phase 1) Fresolimumab 3 mg/kg, (Phase 2) Fresolimumab

Primary outcome

Number of Participants Experiencing Dose Limiting Toxicities (DLTs) of Fresolimumab When Combined With SABR (Phase I)
Time frame: 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
Time frame: 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.

1 secondary outcome

Number of Participants With Late Radiation Induced Fibrosis (Phase 1 Patients)
Time frame: 12 months

Results and safety

Results posted to the registry on 27 Mar 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
(Phase 1) Fresolimumab 3 mg/kg	5	4
(Phase 1) Fresolimumab 1 mg/kg	0	0
(Phase 2) Fresolimumab	0	0

Primary outcome: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) of Fresolimumab When Combined With SABR (Phase I)

Time frame: Up to 30 days. Count of participants. Unit: Participants

Measure	(Phase 1) Fresolimumab 3 mg/kg n = 5
Value	0

Primary outcome: Number of Participants With Late Radiation Induced Fibrosis

Time frame: 12 months. Count of participants. Unit: Participants

Measure	(Phase 2) Fresolimumab n = 15
Value	5

Population analysed: Patients who met criteria to be considered for endpoint analysis.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 12 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
(Phase 1) Fresolimumab 3 mg/kg	0 of 5 (0%)	5 of 5 (100%)	4 of 5
(Phase 2) Fresolimumab	6 of 19 (31.6%)	15 of 19 (78.9%)	5 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Maximilian Diehn principal investigator

Stanford Cancer Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Dose Limiting Toxicities (DLTs) of Fresolimumab When Combined With SABR (Phase I) (time frame: Up to 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02581787.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2024.