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

NCT02581787 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB-34863NCI-2015-01726LUN0071
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  12 months

Secondary Outcomes (1)

• Number of Participants With Late Radiation Induced Fibrosis (Phase 1 Patients)

  12 months

Study Arms (3)

(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.

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.

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.

Biological: Fresolimumab; Radiation: Stereotactic Body Radiation Therapy

Interventions

Fresolimumab BIOLOGICAL

Given IV

Also known as: 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

(Phase 1) Fresolimumab 1 mg/kg; (Phase 1) Fresolimumab 3 mg/kg; (Phase 2) Fresolimumab

Stereotactic Body Radiation Therapy RADIATION

Undergo SABR

Also known as: SBRT

(Phase 1) Fresolimumab 1 mg/kg; (Phase 1) Fresolimumab 3 mg/kg; (Phase 2) Fresolimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maximilian Diehn: lead
• Varian Medical Systems: collaborator

Study Sites (1)

Stanford University, School of Medicine

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

fresolimumab; Immunoglobulin G; Disulfides; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Maximilian Diehn, MD, PhD
• Organization: Stanford University

diehn@stanford.edu

(650) 721-1550

Study Officials

• Maximilian Diehn

  Stanford Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Radiation Oncology

Study Record Dates

• First Submitted: October 16, 2015
• First Posted: October 21, 2015
• Study Start: August 1, 2016
• Primary Completion: March 2, 2023
• Study Completion: March 2, 2023
• Last Updated: March 27, 2024
• Results First Posted: March 27, 2024

Record last verified: 2024-03

Locations

US (1)