Carcinoma, Non-Small-Cell Lung Clinical Trial
Official title:
Phase II Study Evaluating The Safety And Response To Neoadjuvant Dasatinib In Early Stage Non-Small Cell Lung Cancer (NSCLC).
Src expression has been identified in a majority of Non-Small Cell Lung Cancer (NSCLC) cell
lines and there is preclinical evidence that Src family kinases may be important in hypoxic
growth and angiogenesis in NSCLC. We hypothesize that the inhibition of Src pathway with
dasatinib will demonstrate anti-tumor activity in early stage NSCLC, with a tolerable safety
profile.
Patients will receive dasatinib, a Src inhibitor, for 3 weeks prior to surgical resection
for early stage NSCLC. Fresh frozen tumor tissue is needed for genomic analysis. If fresh
frozen tumor tissue is not available from the initial diagnosis, a biopsy will be required
to participate in this trial. A second tumor sample will be obtained at time of surgical
resection to evaluate for changes in genomic expression profiles.
Patients will be eligible to receive 3 months of adjuvant dasatinib therapy after completion
of standard adjuvant therapy or after recovery from surgery if no standard adjuvant therapy
is given, if there is evidence of neoadjuvant tumor response (radiologic and/or pathologic)
to dasatinib.
Many patients who present with NSCLC are active smokers. Patients who are smoking up until
the time of their surgery experience increased peri-operative complications compared to
patients who have not smoked cigarettes immediately prior to surgery. While this trial will
not be limited to active smokers, the period of smoking cessation prior to surgery is an
attractive window of opportunity during which the potentially active novel anticancer
therapy dasatinib can be offered to the patient.
This is a phase II study of dasatinib, a targeted biologic agent, known to inhibit Src. It
is difficult to assess outcome in phase II adjuvant trials because there is no measurable
disease to evaluate efficacy and there are many variables that could confound comparing
survival of subjects on trial to historical controls. Therefore, after a fresh frozen tumor
tissue sample is obtained for genomic analysis, we plan to treat subjects with neoadjuvant
dasatinib and then measure tumor response to therapy prior to surgery. Resected tumor will
also be assessed for pathologic response as well as for changes in genomic expression
patterns.
Subjects will be treated with neoadjuvant dasatinib 70 mg PO twice daily for 3 weeks, with a
mandatory minimum of 3 days (72 hours) off of study drug prior to surgical resection.
Imaging studies will be done pre-treatment and pre-surgery to assess radiologic response to
therapy. The surgical specimen will be evaluated for pathologic response. A tumor tissue
sample will be obtained from the surgical specimen for genomic analysis and will be
evaluated for changes in genomic expression profiles.
Patients whose tumors have a response to neoadjuvant dasatinib therapy might benefit with
better cancer control if they receive a potentially therapeutic course of adjuvant
dasatinib. Patients that have at least a 15% decrease or better objective response, without
evidence of progression to neoadjuvant dasatinib (per tumor evaluation pre-surgery) or
pathologic response (as defined as ≥30% tumor necrosis or cell death) to neoadjuvant
dasatinib therapy will be eligible to receive dasatinib 70 mg twice daily for 90 days after
the completion of standard adjuvant therapy or after recovery from surgery if no standard
adjuvant therapy is given. Patients will be followed for approximately 30 days after the
last dose of dasatinib to assess toxicity.
Response will be evaluated in Src regulated and Src deregulated cohorts of tumors. If
responses to neoadjuvant dasatinib occur, then accrual to either or both cohorts will be
expanded. If there are no responses to neoadjuvant dasatinib in the cohort groups, then
accrual to either or both cohorts will be stopped. The results of this study may be useful
in designing future studies in early stage NSCLC using dasatinib alone or in combination
with chemotherapy.
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04879849 -
A Study of TAK-676 With Pembrolizumab After Radiation Therapy to Treat a Number of Cancers
|
Phase 1 | |
Completed |
NCT04426825 -
A Study of Atezolizumab in Combination With Bevacizumab in Patients With EGFR Mutation Positive Stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer
|
Phase 2 | |
Terminated |
NCT03166631 -
A Trial to Find the Safe Dose for BI 891065 Alone and in Combination With BI 754091 in Patients With Incurable Tumours or Tumours That Have Spread
|
Phase 1 | |
Completed |
NCT02810457 -
Evaluation of FKB238 and Avastin in Patients With Advanced/Recurrent Non-squamous Non-small Cell Lung Cancer
|
Phase 3 | |
Completed |
NCT02864394 -
Study of Pembrolizumab Versus Docetaxel in Participants Previously Treated for Non-Small Cell Lung Cancer (MK-3475-033/KEYNOTE-033)
|
Phase 3 | |
Recruiting |
NCT04592523 -
A Study of Usage of Brigatinib in the Treatment of Adult Participants for Approved Indications In South Korea
|
||
Recruiting |
NCT04838548 -
A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With EGFR-Positive Advanced Non-Small Cell Lung Cancer
|
Phase 2 | |
Recruiting |
NCT04077463 -
A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer
|
Phase 1 | |
Recruiting |
NCT05167604 -
Clinical Value of MRD Monitoring for Adjuvant Therapy in Postoperative NSCLC
|
||
Recruiting |
NCT04603807 -
A Study to Compare the Efficacy and Safety of Entrectinib and Crizotinib in Participants With Advanced or Metastatic ROS1 Non-small Cell Lung Cancer (NSCLC) With and Without Central Nervous System (CNS) Metastases
|
Phase 3 | |
Completed |
NCT04948411 -
Durvalumab as Maintenance in Patients Who Received Chemoradiotherapy for Unresectable Stage III NSCLC: Real World Data From an Expanded Access Program in Brazil
|
||
Active, not recruiting |
NCT04487080 -
A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
|
Phase 3 | |
Not yet recruiting |
NCT04255836 -
Durvalumab Combined With Chemotherapy and Stereotactic Body Radiotherapy (SBRT) in Patients With Oligometastatic Non-small Cell Lung Cancer (NSCLC)
|
Phase 2 | |
Completed |
NCT01953913 -
Afatinib (BIBW 2992) in Advanced Non-Small Cell Lung Cancer Patients With EGFR Mutation
|
Phase 3 | |
Recruiting |
NCT05715229 -
Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy
|
Phase 2 | |
Recruiting |
NCT04931654 -
A Study to Assess the Safety and Efficacy of AZD7789 in Participants With Advanced or Metastatic Solid Cancer
|
Phase 1/Phase 2 | |
Suspended |
NCT05421936 -
Osimertinib for NSCLC With Uncommon EGFR Mutations
|
||
Completed |
NCT02847377 -
A Positron Emission Tomography (PET) Imaging Agent [18F]-ODS2004436 as a Marker of EGFR Mutation in Subjects With NSCLC
|
N/A | |
Completed |
NCT04427072 -
Study of Capmatinib Efficacy in Comparison With Docetaxel in Previously Treated Participants With Non-small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutation
|
Phase 3 | |
Recruiting |
NCT04823377 -
Impact of a Process Optimizing the Decision to Continue or Stop Cancer Treatments in Patients With Advanced Non-small Cell Lung Cancer.
|
N/A |