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.
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
Drug | Synonyms | Arms |
---|
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 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.
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
Name | Type | Description | Interventions |
---|
SBRT + FLT3 Ligand Immunotherapy | Experimental | Patients will be treated with stereotactic body radiotherapy (SBRT) to a single pulmonary or extrapulmonary 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: | Active, not recruiting |
Lead Sponsor: | Albert Einstein College of Medicine |
Last Updated
September 1, 2020