Clinical Trial: NCT02581787 - My Cancer Genome

NCT02581787

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.

Related Conditions:

Non-Small Cell Lung Carcinoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT02581787

Trial Eligibility

Document

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: IRB-34863
SECONDARY ID: NCI-2015-01726
SECONDARY ID: LUN0071
SECONDARY ID: IRB-34863
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

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.

      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	In Phase 1: Patients receive fresolimumab IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12 in total of 5 subjects. In Phase 2: . 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.	Fresolimumab

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.

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:	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.

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	Maximilian Diehn

Last Updated

December 8, 2020

Clinical Trials /

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