Clinical Trials /

FLT3 Ligand Immunotherapy and Stereotactic Radiotherapy for Advanced Non-small Cell Lung Cancer

NCT02839265

Description:

Based on promising data from our laboratory demonstrating synergy between ablative local radiotherapy and FLT3 ligand immunotherapy in murine NSCLC models, investigators are performing a phase II study combining FLT3L immunotherapy and SBRT for patients with advanced NSCLC that has progressed following standard systemic therapy. All patients will receive daily subcutaneous injections of CDX-301 (75 µg/kg) for 5 days, beginning on the first day of SBRT. SBRT will be delivered to a single pulmonary or extrapulmonary lesion. The SBRT regimen will depend on the size and location of the target lesion. The primary endpoint will be progression-free survival at 4 months, defined using immune-related response criteria (irRC). A total of 29 patients will be enrolled.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: FLT3 Ligand Immunotherapy and Stereotactic Radiotherapy for Advanced Non-small Cell Lung Cancer
  • Official Title: FLT3 Ligand Immunotherapy and Stereotactic Radiotherapy for Advanced Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2015-5267
  • NCT ID: NCT02839265

Conditions

  • Non-small Cell Lung Cancer (NSCLC)

Interventions

DrugSynonymsArms
FLT3 Ligand Therapy (CDX-301)SBRT + FLT3 Ligand Immunotherapy

Purpose

Based on promising data from our laboratory demonstrating synergy between ablative local radiotherapy and FLT3 ligand immunotherapy in murine NSCLC models, investigators are performing a phase II study combining FLT3L immunotherapy and SBRT for patients with advanced NSCLC that has progressed following standard systemic therapy. All patients will receive daily subcutaneous injections of CDX-301 (75 µg/kg) for 5 days, beginning on the first day of SBRT. SBRT will be delivered to a single pulmonary lesion. Depending on the size and location of the target lesion, the SBRT regimen will be 34 Gy x 1 (peripheral tumors smaller than 2 cm and not adjacent to the chest wall), 18 Gy x 3 (peripheral tumors not eligible for 34 Gy x 1), or 10 Gy x 5 (central tumors). The primary endpoint will be progression-free survival at 4 months, defined using immune-related response criteria (irRC). A total of 29 patients will be enrolled.

Detailed Description

      Primary Objective

        -  To explore the efficacy of combining stereotactic body radiotherapy (SBRT) with FLT3
           ligand immunotherapy for advanced non-small cell lung cancer (NSCLC).

      Secondary Objectives

        -  To establish the feasibility and safety of combining SBRT with FLT3 ligand
           immunotherapy for advanced NSCLC.

        -  To quantify and evaluate potential surrogate outcomes for clinical efficacy of this
           treatment approach, including radiographic responses, immunologic responses, and
           circulating tumor cell levels.
    

Trial Arms

NameTypeDescriptionInterventions
SBRT + FLT3 Ligand ImmunotherapyExperimentalPatients will be treated with stereotactic body radiotherapy (SBRT) to a single pulmonary lesion as well as FLT3 immunotherapy. FLT3 Ligand Therapy (CDX-301) Daily subcutaneous injections of CDX-301 (75 ug/kg) will be administered for 5 days, beginning on the first day of SBRT. Additional cycles of SBRT (to distinct lesions) and CDX-301 may be administered every 2-4 months to subjects who demonstrate evidence of clinical benefit (lack of treatment-related toxicity and no disease progression). Study therapy will be discontinued in cases of treatment-related toxicity or disease progression.
  • FLT3 Ligand Therapy (CDX-301)

Eligibility Criteria

        Inclusion Criteria:

          -  AJCC stage 3 or 4 histologically proven NSCLC not amenable to curative therapy

          -  Age >= 18 years

          -  Prior treatment with at least one standard chemotherapy regimen or targeted agent
             prior to enrollment

          -  Radiological assessment within 21 days prior to study entry demonstrating measurable
             disease that includes at least one pulmonary lesion . 1 cm in greatest dimension that
             would be amenable to SBRT and at least one measurable lesion that would be outside of
             the SBRT treatment fields

          -  History/physical examination within 30 days prior to registration

          -  ECOG performance status 0-2

          -  Signed, written informed consent

        Exclusion Criteria:

          -  Less than 21 days between registration and the last receipt of chemotherapy,
             biotherapy, immunotherapy, radiotherapy (excluding palliative radiotherapy), or major
             surgery. Prior receipt of immunomodulatory therapy (eg: nivolumab) is permitted, as
             long as there has been a 21 day washout period following the most recent treatment.

          -  Untreated central nervous system metastases. Patients with a history of brain
             metastases must have had no CNS-directed therapy within the past 60 days and
             radiological assessment within 30 days of study entry demonstrating a lack of
             progressive CNS disease

          -  Ongoing or recent (within 21 days prior to study entry) use of high dose oral
             corticosteroids (.2 mg of dexamethasone daily or equivalent). Intranasal and/or
             inhaled corticosteroid use is permitted.

          -  Any unresolved CTCAE grade >2 toxicity from previous anti-cancer therapy. Patients
             with irreversible toxicity that is not reasonably expected to be exacerbated by study
             therapy (eg, hearing loss)may be enrolled after discussion with the principal
             investigators.

          -  History of allogeneic organ transplant or autoimmune disease

          -  Active malignancy, other than NSCLC, for which systemic therapy is indicated. History
             of adequately treated local basal cell or squamous cell carcinoma of the skin,
             cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer
             without known metastatic disease and with no requirement for therapy asides from
             hormonal therapy, adequately treated stage 1 or 2 cancer currently in complete
             remission, or any other cancer that has been in complete remission for >= 5 years is
             permitted.

          -  Uncontrolled intercurrent illness including, but not limited to, symptomatic
             congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia,
             or psychiatric illness/social situation that would limit compliance with study
             requirements as judged by the treating physicians

          -  The following laboratory results, within 10 days of first study drug administration:

               -  Hemoglobin . 9.0 g/dL, Absolute neutrophil count . 1.5 x 109/L, Platelet count .
                  100 x 109/L

               -  Serum creatinine . 1.5 x ULN and creatinine clearance (by Cockcroft-Gault
                  formula) < 60 mL/min

          -  Women of child bearing potential: positive pregnancy test (serum)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival
Time Frame:4 Months
Safety Issue:
Description:The primary endpoint is progression-free survival rate at four months (PFS4), defined as the rate estimate of the percentage of patients who are alive and progression-free at 16 weeks (~4 months) after initiation of study therapy.

Secondary Outcome Measures

Measure:Dose limiting toxicities (DLTs)
Time Frame:30 days
Safety Issue:
Description:Dose limiting toxicities (DLTs): For the purposes of this study, a DLT will be defined as any treatment-emergent grade 3-5 toxicity, scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and occurring within 30 days after treatment with SBRT in combination with FLT3 ligand therapy.Asymptomatic laboratory abnormalities (eg: leukocytosis) that do not require intervention will not be counted as DLTs. For subjects who receive more than one "cycle" of SBRT and FLT3 ligand, only adverse events that occur after the first cycle will be scored as potential DLTs.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Albert Einstein College of Medicine, Inc.

Last Updated

July 18, 2016